bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding family planning decision-making: perspectives of providers and community stakeholders from Istanbul, Turkey
Authors: Karadon Duygu , Esmer Yilmaz , Okcuoglu Bahar Ayca , Kurutas Sebahat , Baykal Simay Sevval , Huber-Krum Sarah , Canning David , Shah Iqbal
Published: October 2021

Background

A number of factors may determine family planning decisions; however, some may be dependent on the social and cultural context. To understand these factors, we conducted a qualitative study with family planning providers and community stakeholders in a diverse, low-income neighborhood of Istanbul, Turkey.

Methods

We used purposeful sampling to recruit 16 respondents (eight family planning service providers and eight community stakeholders) based on their potential role and influence on matters related to sexual and reproductive health issues. Interviews were audio-recorded with participants' permission and subsequently transcribed in Turkish and translated into English for analysis. We applied a multi-stage analytical strategy, following the principles of the constant comparative method to develop a codebook and identify key themes.

Results

Results indicate that family planning decision-making—that is, decision on whether or not to avoid a pregnancy—is largely considered a women’s issue although men do not actively object to family planning or play a passive role in actual use of methods. Many respondents indicated that women generally prefer to use family planning methods that do not have side-effects and are convenient to use. Although women trust healthcare providers and the information that they receive from them, they prefer to obtain contraceptive advice from friends and family members. Additionally, attitude of men toward childbearing, fertility desires, characteristics of providers, and religious beliefs of the couple exert considerable influence on family planning decisions.

Conclusions

Numerous factors influence family planning decision-making in Turkey. Women have a strong preference for traditional methods compared to modern contraceptives. Additionally, religious factors play a leading role in the choice of the particular method, such as withdrawal. Besides, there is a lack of men’s involvement in family planning decision-making. Public health interventions should focus on incorporating men into their efforts and understanding how providers can better provide information to women about contraception.
Significance of the viral load of high-risk HPV in the diagnosis and prediction of cervical lesions: a retrospective study
Authors: Liu Yang , Xu Changjun , Pan Jing , Sun Chunyi , Zhou Honglin , Meng Yushi
Published: October 2021

Background

The significance of HPV viral load in the detection of cervical lesions is still controversial. This study analyzed the correlation between the high-risk HPV viral load and different cervical lesion degrees.

Methods

This retrospective study included women positive for high-risk HPV DNA and screened for cervical lesions between 01/2015 and 06/2018. The high-risk HPV DNA load was measured by the second-generation Hybrid Capture technology and classified as low, moderate, and high. Colposcopy and biopsy were performed in all patients. The patients were grouped as normal, cervical intraepithelial neoplasia (CIN) grade 1, CIN grade 2, CIN grade 3, and cervical cancer. Multivariable logistic regression was performed to explore the association between high-risk HPV DNA load and cervical lesions. The odds ratios (ORs) represent the odds for increasing from low to high viral load.

Results

Finally, 265 patients were grouped as normal (n = 125), CIN 1 (n = 51), CIN 2 (n = 23), CIN 3 (n = 46), and cervical cancer (n = 20). Among them, 139 (52.5%) had a low viral load, 90 (34.0) had a moderate viral load, and 36 (13.4%) had a high viral load. Taking the normal control group as a reference, a high viral load was an independent factor for CIN 1 (OR = 3.568, 95% CI: 1.164–10.941, P = 0.026), CIN 2 (OR = 6.939, 95% CI: 1.793–26.852, P = 0.005), CIN 3 (OR = 7.052, 95% CI: 2.304–21.586, P = 0.001), and cervical cancer (OR = 8.266, 95% CI: 2.120–32.233, P = 0.002).

Conclusions

Among women who underwent cervical biopsy, higher high-risk HPV viral load in cervical lesions was associated with a higher risk of high-grade cervical lesions.
Effect of educational intervention on improvement of physical activities of middle-aged women
Authors: Rakhshani Tayebeh , Khiyali Zahra , Masrurpour Fatemeh , Khani Jeihooni Ali
Published: October 2021

Background

Regular physical activity has important health benefits for women. The present study aimed to investigate the effect of theory-based educational interventions on the improvement of physical activities of middle-aged women.

Methods

This experimental study was conducted on 160 middle-aged women referred to Ahwaz health centers Iran in 2017 who were selected through the cluster sampling method. They were randomly divided into two groups: intervention (n = 80) and control (n = 80). The educational intervention for the experimental group consisted of 4 consultation and 4 follow-up sessions. The study outcomes included physical activity change, self-efficacy, decision-making balance, and the International Physical Activity Questionnaire, which were measured before the intervention and 2 months after that. The data were analyzed using the SPSS19 software as well as the Chi-square, independent t-test and paired t-test.

Results

After the intervention, the mean scores of preparedness for change, decision-making balance, perceived self-efficacy, pre-thinking, thinking, preparation, practice and maintenance were significantly different in both the experimental and control groups (Pvalue < 0.05). The t-test showed that after the educational intervention, the mean score of physical activity was significantly higher in the experimental group than in the control group (726.3 ± 201.6 and 339.8 ± 90.2, respectively) (Pvalue < 0.001).

Conclusion

The findings of this study showed that the theory-based educational intervention was effective on the improvement of the middle-aged women’s physical activities. Therefore, it is suggested that a theory-based educational program be designed and implemented in order to increase the physical activities of this group.
Self-administered subcutaneous medroxyprogesterone acetate for improving contraceptive outcomes: a systematic review and meta-analysis
Authors: Nabhan Ashraf , Elshafeey Farida , Mehrain Luna Marion , Kabra Rita , Elshabrawy Amal
Published: October 2021

Background

Subcutaneous depot medroxyprogesterone acetate is an easy-to-use injectable contraceptive. A trained person can administer it, including women through self-injection. The objective of this systematic review and meta-analysis was to assess the effectiveness and safety of self-injection versus provider-administered subcutaneous depot medroxyprogesterone acetate for improving continuation of contraceptive use.

Methods

We searched for randomized controlled trials on November 1, 2020 in Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, Embase, Web of Science, Scopus, Open Grey, clinical trials registries, and reference lists of relevant studies. We did not impose any search restrictions. We included randomized trials comparing self- versus provider-administered subcutaneous depot medroxyprogesterone acetate. Two authors independently screened trials, extracted data, and assessed the risk of bias in the included studies. We used risk ratio and 95% confidence intervals for dichotomous outcomes.

Results

We identified 3 randomized trials (9 reports; 1264 participants). The risk of bias in the included studies was low except for performance bias and detection bias of participant-reported outcomes in unmasked trials. Self-administration, compared to provider-administration, increased continuation of contraceptive use (risk ratio 1.35; 95% confidence intervals 1.10–1.66); moderate-certainty evidence). Self-injection appears to be making more of an impact on continuation for younger women compared to women 25 years and older and on women living in low and middle income compared to high income countries. There was no subgroup difference by the type of care provider (community health worker vs. clinic-based provider).

Conclusions

Self-injection of subcutaneous depot medroxyprogesterone acetate probably improves continuation of contraceptive use. The effects on other outcomes remain uncertain because of the very low certainty of evidence.
Effect of physical activity and exercise on endometriosis-associated symptoms: a systematic review
Authors: Tennfjord Merete Kolberg , Gabrielsen Rakel , Tellum Tina
Published: October 2021

Background

Endometriosis is a common benign gynecological disease that has the potential to debilitate due to pain and reduced quality of life. Treatment modalities such as hormones and surgery have limitations and do not treat all dimensions of the problems caused by endometriosis, and physical activity (PA) and exercise have been suggested as alternative treatments. Aim of this study was to perform a systematic review and meta-analysis to assess the effect of PA and exercise on endometriosis-associated symptoms.

Methods

Eleven databases were searched systematically. Study selection, quality assessment, and data extraction were carried out by two independent researchers in accordance with PRISMA guidelines. Eligibility criteria were women with diagnosed endometriosis receiving an intervention (PA and/or exercise). The primary outcome was pain intensity, but all outcomes were accepted.

Results

This study screened 1045 citations for eligibility. Four interventional studies were identified, of which one showed fatal design flaws and so was excluded. Three studies, two randomized controlled trials (RCT) and one pre-post study with no control group, involving 109 patients were included in a descriptive synthesis. The interventions included flexibility and strength training, cardiovascular fitness, and yoga, and were performed from one to four times per week for a total duration of 8–24 weeks, with or without supervision. Only one study found improvements in pain intensity. One study showed decreases in stress levels. Due to the heterogeneity of the study outcomes and measures, as well as confounding factors, a quantitative meta-analysis could not be performed.

Conclusion

The effect of PA and exercise as treatments for endometrioses-associated symptoms could not be determined due to significant limitations of the included studies. Future research should be based on RCTs of high methodological quality, measuring and reporting relevant core outcomes such as pain, improvements in symptoms and quality of life, and acceptability and satisfaction from the perspectives of patients. Furthermore, these outcomes need to be measured using reliable and validated tools.

Trial registration number

CRD42021233138.
Anti-apoptotic effect of Buchholzia coriacea Engl. stem back extracts on AsPC-1 and mechanisms of action
Authors: Onohuean Hope , Adisa Rahmat Adetutu , Alagbonsi Abdullateef Isiaka
Published: October 2021

Ethnopharmacological relevance

Buchholzia coriacea Engl. is popularly called wonderful cola due to its wide ethnomedicinal use for the treatment of various ailments. We investigated the possible cytotoxic effect of its various fractions on human pancreatic cancer cell (AsPC-1) and also determined its mechanisms of action.

Materials and methods

The AsPC-1 cells were cultivated and separately treated with 5-fluorouracil (5-FU) or Buchholzia coriacea Engl. bark (BC) (ethanol, aqueous, chloroform or ethyl acetate extract) for 72 h. Cell viability, caspase 3 and mitochondrial membrane potential (ΔΨm) were determined in vitro after the treatment. Nitric oxide (NO) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals’ scavenging property, ferric reducing power and lipid peroxidation assays were also done to examine the antioxidant effect of BC in vitro.

Results

Various extracts of BC, especially at 2500 μg/ml and 5000 μg/ml, increased the AsPC-1 viability while 5-FU decreased it. The activity of caspase 3 was increased by 5-FU but reduced by all concentrations of various extracts of BC. Incubation of AsPC-1 with 5-FU showed the majority of cells having the monomeric form of JC-1 dye (bright green fluorescence), which indicated de-energized mitochondria. However, fluorescence photomicrograph of cells incubated with different concentrations (20, 40 and 100 μg/ml) of BC extracts (aqueous, ethanol, chloroform and ethyl acetate) showed strong JC-1 aggregation (yellow), which indicated mitochondria with intact membrane potentials. BC extracts also scavenged NO and DPPH radicals, inhibited lipid peroxidation and increased ferric reduction, though not as much as ascorbic acid.

Conclusion

This study suggests that BC elicits anti-apoptotic activity in AsPC-1 by increasing cell viability, decreasing caspase 3 activity, stabilizing the ∆Ψm, and scavenging free radicals. Even though BC is used ethnomedicinally as anti-cancer agent, our findings in the present study suggest that it has pro-cancer potential in-vitro, especially on pancreatic cells. Its anti-apoptotic activity in AsPC-1 could be of clinical significance, especially to counteract the effect of apoptotic agents on pancreatic cells.
Familiarity and genetic literacy among medical students in Indonesia
Authors: Swandayani Yolanda Marthia , Cayami Ferdy Kurniawan , Winarni Tri Indah , Utari Agustini
Published: October 2021

Background

There is a lack of genetic knowledge among health care professionals especially in some developing countries such as Indonesia. Based on our experience, genetic disorders receive less attention in medical education and professionals. This study aims to determine the familiarity and literacy of genetics among medical students in Indonesia.

Methods

A total of 1003 Indonesian medical (pre-clinical and clinical) students completed the Rapid Estimate of Adult Literacy in Genetics (REAL-G) questionnaire with a total score of seven for familiarity and eight for genetic literacy. The Mann-Whitney U test was used to compare the familiarity and genetic literacy scores between pre-clinical and clinical students.

Results

The average scores of familiarity and genetic literacy were 5.63 ± 0.96 and 6.37 ± 0.83, respectively. Genetic familiarity was higher (p = 0.043) among clinical students than pre-clinical students, while there was no significant difference in genetic literacy (p = 0.362) between pre-clinical and clinical students. Genetic familiarity does not impact the level of genetic literacy. However, medical students’ genetic literacy is influenced by demographic characteristics, such as age, sex, university type, genetic learning experience, university accreditation, and university location.

Conclusions

In general, Indonesian medical students have relatively good familiarity and literacy in genetics although further study is necessary to accurately measure the genetic familiarity and literacy in medical students and general public.
A Spanish adaptation of the Quality in Psychiatric Care—Inpatient (QPC-IP) instrument: Psychometric properties and factor structure
Authors: Sanchez-Balcells Sara , Lluch-Canut Maria-Teresa , Domínguez del Campo Marta , Moreno-Poyato A. R. , Tomás-Jiménez M. , Lundqvist Lars-Olov , Schröder Agneta , Puig-Llobet Montserrat , Roldan-Merino J. F.
Published: October 2021

Background and aim

Western countries share an interest in evaluating and improving quality of care in the healthcare field. The aim was to develop and examine the psychometric properties and factor structure of the Spanish version of the Quality in Psychiatric Care–Inpatient (QPC-IP) instrument.

Methods

A psychometric study was conducted, translating the QPC-IPS instrument into Spanish, revision of the instrument by a panel of experts, and assessing its psychometric properties. 150 psychiatric inpatients completed the QPC-IP. Test-retest reliability was assessed by re-administering the questionnaire to 75 of these patients.

Results

After conducting pilot testing and a cognitive interview with 30 inpatients, it was determined that the QPC-IPS was adequate and could be self-administered. A Cronbach’s alpha of 0.94 was obtained for the full instrument and values of 0.52–0.89 for the various dimensions of the questionnaire. Test re test reliability: The Intraclass Correlation Coefficient for the full questionnaire was 0.69, while for the individual dimensions values between 0.62 and 0.74 were obtained, indicating acceptable temporal stability. Convergent validity was analysed using 10-point numerical satisfaction scale, giving a positive correlation (0.49). Confirmatory factor analysis revealed six factors consistent with the original scale. The Spanish version yielded adequate results in terms of validity and reliability.

Conclusion

Our findings provide evidence of the convergent validity, reliability, temporal stability and construct validity of the Spanish QPC-IP for measuring patient quality in psychiatric care in Spanish hospitals. Hospital administrators can use this tool to assess and identify areas for improvement to enhance quality in psychiatric care.
Attitudes of medical workers in China toward artificial intelligence in ophthalmology: a comparative survey
Authors: Zheng Bo , Wu Mao-nian , Zhu Shao-jun , Zhou Hong-xia , Hao Xiu-lan , Fei Fang-qin , Jia Yun , Wu Jian , Yang Wei-hua , Pan Xue-ping
Published: October 2021

Background

In the development of artificial intelligence in ophthalmology, the ophthalmic AI-related recognition issues are prominent, but there is a lack of research into people’s familiarity with and their attitudes toward ophthalmic AI. This survey aims to assess medical workers’ and other professional technicians’ familiarity with, attitudes toward, and concerns about AI in ophthalmology.

Methods

This is a cross-sectional study design study. An electronic questionnaire was designed through the app Questionnaire Star, and was sent to respondents through WeChat, China’s version of Facebook or WhatsApp. The participation was voluntary and anonymous. The questionnaire consisted of four parts, namely the respondents’ background, their basic understanding of AI, their attitudes toward AI, and their concerns about AI. A total of 562 respondents were counted, with 562 valid questionnaires returned. The results of the questionnaires are displayed in an Excel 2003 form.

Results

There were 291 medical workers and 271 other professional technicians completed the questionnaire. About 1/3 of the respondents understood AI and ophthalmic AI. The percentages of people who understood ophthalmic AI among medical workers and other professional technicians were about 42.6 % and 15.6 %, respectively. About 66.0 % of the respondents thought that AI in ophthalmology would partly replace doctors, about 59.07 % having a relatively high acceptance level of ophthalmic AI. Meanwhile, among those with AI in ophthalmology application experiences (30.6 %), above 70 % of respondents held a full acceptance attitude toward AI in ophthalmology. The respondents expressed medical ethics concerns about AI in ophthalmology. And among the respondents who understood AI in ophthalmology, almost all the people said that there was a need to increase the study of medical ethics issues in the ophthalmic AI field.

Conclusions

The survey results revealed that the medical workers had a higher understanding level of AI in ophthalmology than other professional technicians, making it necessary to popularize ophthalmic AI education among other professional technicians. Most of the respondents did not have any experience in ophthalmic AI but generally had a relatively high acceptance level of AI in ophthalmology, and there was a need to strengthen research into medical ethics issues.
Barriers to symptom management care pathway implementation in pediatric Cancer
Authors: Dupuis L. Lee , Grimes Allison , Vettese Emily , Klesges Lisa M. , Sung Lillian
Published: October 2021

Background

Objectives were to describe barriers to pediatric cancer symptom management care pathway implementation and the impact of the COVID-19 pandemic on clinical research evaluating their implementation.

Methods

We included 25 pediatric oncology hospitals in the United States that supported a grant submission to perform a cluster randomized trial in which the intervention encompassed care pathways for symptom management. A survey was distributed to site principal investigators prior to randomization to measure contextual elements related to care pathway implementation. Questions included the inner setting measures of the Consolidated Framework for Implementation Research (CFIR), study-specific potential barriers and the impact of the COVID-19 pandemic on clinical research. The Wilcoxon rank sum test was used to compare characteristics of institutions that agreed that their department supported the implementation of symptom management care pathways vs. institutions that did not agree.

Results

Of the 25 sites, one withdrew because of resource constraints and one did not respond, leaving 23 institutions. Among the seven CFIR constructs, the least supported was implementation climate; 57% agreed there was support, 39% agreed there was recognition and 39% agreed there was prioritization for symptom management care pathway implementation at their institution. Most common barriers were lack of person-time to create care pathways and champion their use (35%), lack of interest from physicians (30%) and lack of information technology resources (26%). Most sites reported no negative impact of the COVID-19 pandemic across research activities. Sites with fewer pediatric cancer patients were more likely to agree that staff are supported to implement symptom management care pathways (P = 0.003).

Conclusions

The most commonly reported barriers to implementation were lack of support, recognition and prioritization. The COVID-19 pandemic may not be a major barrier to clinical research activities in pediatric oncology.
The use of accelerometer-based wearable activity monitors in clinical settings: current practice, barriers, enablers, and future opportunities
Authors: Maher Carol , Szeto Kimberley , Arnold John
Published: October 2021

Background

Wearable activity monitors (WAMs, e.g. Fitbits and research accelerometers) show promise for helping health care professionals (HCPs) measure and intervene on patients’ activity patterns. This study aimed to describe the clinical use of WAMs within South Australia, barriers and enablers, and future opportunities for large-scale clinical use.

Methods

A descriptive qualitative study was undertaken using semi-structured interviews. Participants were HCPs with experience using WAMs in South Australian clinical settings. Commencing with participants identified through the research team’s professional networks, snowball recruitment continued until all identified eligible HCPs had been invited. Semi-structured interviews were used to explore the research aims, with quantitative data analysed descriptively, and qualitative data analysed thematically.

Results

18 participants (physiotherapistsn = 8, exercise physiologistsn = 6, medical consultantsn = 2, and research personnel recommended by medical consultantsn = 2), represented 12 discrete “hubs” of WAM use in clinical practice, spanning rehabilitation, orthopaedics, geriatrics, intensive care, and various inpatient-, outpatient-, community-based hospital and private-practice settings. Across the 12 hubs, five primarily used Fitbits® (various models), four used research-grade accelerometers (e.g. GENEActiv, ActivPAL and StepWatch accelerometers), one used Whoop Bands® and another used smartphone-based step counters. In three hubs, WAMs were used to observe natural activity levels without intervention, while in nine they were used to increase (i.e. intervene on) activity. Device selection was typically based on ease of availability (e.g. devices borrowed from another department) and cost-economy (e.g. Fitbits® are relatively affordable compared with research-grade devices). Enablers included device characteristics (e.g. accuracy, long battery life, simple metrics such as step count) and patient characteristics (e.g. motivation, rehabilitation population, tech-savvy), whilst barriers included the HCPs’ time to download and interpret the data, multidisciplinary team attitudes and lack of protocols for managing the devices.

Conclusions

At present, the use of WAMs in clinical practice appears to be fragmented and ad hoc, though holds promise for understanding patient outcomes and enhancing therapy. Future work may focus on developing protocols for optimal use, system-level approaches, and generating cost-benefit data to underpin continued health service funding for ongoing/wide-spread WAM use.
Mental health service engagement with family and carers: what practices are fundamental?
Authors: Maybery Darryl , Jaffe Irene Casey , Cuff Rose , Duncan Zoe , Grant Anne , Kennelly Melissa , Ruud Torleif , Skogoy Bjorg Eva , Weimand Bente , Reupert Andrea
Published: October 2021

Background

Substantial and important benefits flow to all stakeholders, including the service user, when mental health services meaningfully engage with carers and family members. Government policies around the world clearly supports inclusiveness however health service engagement with family and carers remains sporadic, possibly because how best to engage is unclear. A synthesis of currently used surveys, relevant research and audit tools indicates seven core ways that families and carers might be engaged by health services. This study sought to confirm, from the perspective of family and carers, the importance of these seven health service engagement practices.

Methods

In a mixed method online survey, 134 family members and carers were asked what they received and what they wanted from mental health services. Participants also quantified the importance of each of the seven core practices on a 0–100 point likert scale.

Results

Almost 250 verbatim responses were deductively matched against the seven themes, with additional unaligned responses inductively categorised. The findings triangulate with multiple diverse literatures to confirm seven fundamental engagement practices that carers and family want from health services. Conceptually, the seven practices are represented by two broad overarching practice themes of (i) meeting the needs of the family member and (ii) addressing the needs of the service user.

Conclusion

Policy, clinical practice, training and future research might encompass the seven core practices along with consideration of the intertwined relationship of family, carers and the service user suggested by the two broader concepts.
Factors associated with needlestick injuries among healthcare workers: implications for prevention
Authors: Alfulayw Kifah Habib , Al-Otaibi Sultan T. , Alqahtani Hatem A.
Published: October 2021

Background

Our study sought to determine the frequency of Needlestick injuries (NSIs) among Healthcare Workers (HCWs) working at governmental hospital and to study the factors that associated with occurrence of NSIs, and to develop recommendations for a comprehensive program for prevention.

Methods

Retrospective study of all reported cases of NSIs in the period from April 2016 to May 2018 among healthcare workers at a governmental hospital.

Results

Incidence of NSIs over 26 months was 8.4% among all participants. Nurses were the most affected staff (52.5%) resulted commonly from disposing syringes (58.9%). In contrast, the incidence of NSIs among physicians was 24.9% where surgical devices were the primary source of NSIs among them (40%). Failure to complete all required hepatitis B vaccination was common among expatriates of the participants of this study.

Conclusions

NSIs was common among HCWs participated in this study. Preventive measures should be implemented including adequate hepatitis B immunization.
Referral patterns to outpatient child and adolescent mental health services and factors associated with referrals being rejected. A cross-sectional observational study
Authors: Hansen Anna Sofie , Christoffersen Cecilie Haugaard , Telléus Gry Kjaersdam , Lauritsen Marlene Briciet
Published: October 2021

Background

Outpatient child and adolescent mental health services (CAMHS) are faced with the challenge of balancing increasing demands with limited resources. An additional challenge is high rejection rates of referrals which causes frustration for referring agents and families. In order to effectively plan and allocate available resources within CAMHS there is a need for up-to-date knowledge on referral patterns and factors associated with rejection of referrals.

Methods

In this cross-sectional observational study we did a retrospective review of all referrals (n = 1825) for children (0–18) referred for assessment at the outpatient CAMHS of the North Denmark Region in 2018.

Results

The most common referral reasons to CAMHS were attention deficit disorder (ADHD/ADD) (27.9%), autism spectrum disorder (22.4%), affective disorders (14.0%) and anxiety disorders (11.6%). The majority of referrals came from general practitioners, but for neurodevelopmental disorders educational psychologists were the primary referral source. Re-referrals constituted more than a third of all referrals (35.9%). Children in care were overrepresented in this clinical sample and had an increased risk (Adj. OR 2.54) of having their referrals rejected by CAMHS. Referrals from general practitioners were also associated with an increased risk of rejection (Adj. OR 3.29).

Conclusions

A high proportion of children with mental disorders have a repeated need for assessment by CAMHS. There is a need for future research on predictors of re-referral to outpatient services to identify potential targets for reducing re-referral rates as well as research on how to optimize service provision for children with a repeated need for assessment. General practitioners are the main gatekeepers to CAMHS and research on interventions to improve the referral process should be aimed towards general practitioners.
Intensive lactation among women with recent gestational diabetes significantly alters the early postpartum circulating lipid profile: the SWIFT study
Authors: Zhang Ziyi , Lai Mi , Piro Anthony L. , Alexeeff Stacey E. , Allalou Amina , Röst Hannes L. , Dai Feihan F. , Wheeler Michael B. , Gunderson Erica P.
Published: October 2021

Background

Women with a history of gestational diabetes mellitus (GDM) have a 7-fold higher risk of developing type 2 diabetes (T2D). It is estimated that 20-50% of women with GDM history will progress to T2D within 10 years after delivery. Intensive lactation could be negatively associated with this risk, but the mechanisms behind a protective effect remain unknown.

Methods

In this study, we utilized a prospective GDM cohort of 1010 women without T2D at 6-9 weeks postpartum (study baseline) and tested for T2D onset up to 8 years post-baseline (n=980). Targeted metabolic profiling was performed on fasting plasma samples collected at both baseline and follow-up (1-2 years post-baseline) during research exams in a subset of 350 women (216 intensive breastfeeding, IBF vs. 134 intensive formula feeding or mixed feeding, IFF/Mixed). The relationship between lactation intensity and circulating metabolites at both baseline and follow-up were evaluated to discover underlying metabolic responses of lactation and to explore the link between these metabolites and T2D risk.

Results

We observed that lactation intensity was strongly associated with decreased glycerolipids (TAGs/DAGs) and increased phospholipids/sphingolipids at baseline. This lipid profile suggested decreased lipogenesis caused by a shift away from the glycerolipid metabolism pathway towards the phospholipid/sphingolipid metabolism pathway as a component of the mechanism underlying the benefits of lactation. Longitudinal analysis demonstrated that this favorable lipid profile was transient and diminished at 1-2 years postpartum, coinciding with the cessation of lactation. Importantly, when stratifying these 350 women by future T2D status during the follow-up (171 future T2D vs. 179 no T2D), we discovered that lactation induced robust lipid changes only in women who did not develop incident T2D. Subsequently, we identified a cluster of metabolites that strongly associated with future T2D risk from which we developed a predictive metabolic signature with a discriminating power (AUC) of 0.78, superior to common clinical variables (i.e., fasting glucose, AUC 0.56 or 2-h glucose, AUC 0.62).

Conclusions

In this study, we show that intensive lactation significantly alters the circulating lipid profile at early postpartum and that women who do not respond metabolically to lactation are more likely to develop T2D. We also discovered a 10-analyte metabolic signature capable of predicting future onset of T2D in IBF women. Our findings provide novel insight into how lactation affects maternal metabolism and its link to future diabetes onset.

Trial registration

ClinicalTrials.govNCT01967030.
Copy number variation analysis in Chinese children with complete atrioventricular canal and single ventricle
Authors: Zhang Xingyu , Wang Bo , You Guoling , Xiang Ying , Fu Qihua , Yu Yongguo , Zhang Xiaoqing
Published: October 2021

Background

Congenital heart disease (CHD) is one of the most common birth defects. Copy number variations (CNVs) have been proved to be important genetic factors that contribute to CHD. Here we screened genome-wide CNVs in Chinese children with complete atrioventricular canal (CAVC) and single ventricle (SV), since there were scarce researches dedicated to these two types of CHD.

Methods

We screened CNVs in 262 sporadic CAVC cases and 259 sporadic SV cases respectively, using a customized SNP array. The detected CNVs were annotated and filtered using available databases.

Results

Among 262 CAVC patients, we identified 6 potentially-causative CNVs in 43 individuals (16.41%, 43/262), including 2 syndrome-related CNVs (7q11.23 and 8q24.3 deletion). Surprisingly, 90.70% CAVC patients with detected CNVs (39/43) were found to carry duplications of 21q11.2–21q22.3, which were recognized as trisomy 21 (Down syndrome, DS). In CAVC with DS patients, the female to male ratio was 1.6:1.0 (24:15), and the rate of pulmonary hypertension (PH) was 41.03% (16/39). Additionally, 6 potentially-causative CNVs were identified in the SV patients (2.32%, 6/259), and none of them was trisomy 21. Most CNVs identified in our cohort were classified as rare (< 1%), occurring just once among CAVC or SV individuals except the 21q11.2–21q22.3 duplication (14.89%) in CAVC cohort.

Conclusions

Our study identified 12 potentially-causative CNVs in 262 CAVC and 259 SV patients, representing the largest cohort of these two CHD types in Chinese population. The results provided strong correlation between CAVC and DS, which also showed sex difference and high incidence of PH. The presence of potentially-causative CNVs suggests the etiology of complex CHD is incredibly diverse, and CHD candidate genes remain to be discovered.
Metabolic engineering design to enhance (R,R)-2,3-butanediol production from glycerol in Bacillus subtilis based on flux balance analysis
Authors: Vikromvarasiri Nunthaphan , Shirai Tomokazu , Kondo Akihiko
Published: October 2021

Background

Glycerol is a desirable alternative substrate for 2,3-butanediol (2,3-BD) production for sustainable development in biotechnological industries and non-food competitive feedstock. B. subtilis, a “generally recognized as safe” organism that is highly tolerant to fermentation products, is an ideal platform microorganism to engineer the pathways for the production of valuable bio-based chemicals, but it has never been engineered to improve 2,3-BD production from glycerol. In this study, we aimed to enhance 2,3-BD production from glycerol in B. subtilis through in silico analysis. Genome-scale metabolic model (GSM) simulations was used to design and develop the metabolic pathways of B. subtilis. Flux balance analysis (FBA) simulation was used to evaluate the effects of step-by-step gene knockouts to improve 2,3-BD production from glycerol in B. subtilis.

Results

B. subtilis was bioengineered to enhance 2,3-BD production from glycerol using FBA in a published GSM model of B. subtilis, iYO844. Four genes, ackA, pta, lctE, and mmgA, were knocked out step by step, and the effects thereof on 2,3-BD production were evaluated. While knockout of ackA and pta had no effect on 2,3-BD production, lctE knockout led to a substantial increase in 2,3-BD production. Moreover, 2,3-BD production was improved by mmgA knockout, which had never been investigated. In addition, comparisons between in silico simulations and fermentation profiles of all B. subtilis strains are presented in this study.

Conclusions

The strategy developed in this study, using in silico FBA combined with experimental validation, can be used to optimize metabolic pathways for enhanced 2,3-BD production from glycerol. It is expected to provide a novel platform for the bioengineering of strains to enhance the bioconversion of glycerol into other highly valuable chemical products.
A novel tumor doubling time-related immune gene signature for prognosis prediction in hepatocellular carcinoma
Authors: Zhang Genhao , Su Lisa , Lv Xianping , Yang Qiankun
Published: October 2021

Background

Hepatocellular carcinoma (HCC) has become a global health issue of wide concern due to its high prevalence and poor therapeutic efficacy. Both tumor doubling time (TDT) and immune status are closely related to the prognosis of HCC patients. However, the association between TDT-related genes (TDTRGs) and immune-related genes (IRGs) and the value of their combination in predicting the prognosis of HCC patients remains unclear. The current study aimed to discover reliable biomarkers for anticipating the future prognosis of HCC patients based on the relationship between TDTRGs and IRGs.

Methods

Tumor doubling time-related genes (TDTRGs) were acquired from GSE54236 by using Pearson correlation test and immune-related genes (IRGs) were available from ImmPort. Prognostic TDTRGs and IRGs in TCGA-LIHC dataset were determined to create a prognostic model by the LASSO-Cox regression and stepwise Cox regression analysis. International Cancer Genome Consortium (ICGC) and another cohort of individual clinical samples acted as external validations. Additionally, significant impacts of the signature on HCC immune microenvironment and reaction to immune checkpoint inhibitors were observed.

Results

Among the 68 overlapping genes identified as TDTRG and IRG, a total of 29 genes had significant prognostic relevance and were further selected by performing a LASSO-Cox regression model based on the minimum value of λ. Subsequently, a prognostic three-gene signature including HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1), C-type lectin domain family 1 member B (CLEC1B), and Collectin sub-family member 12 (COLEC12) was finally identified by stepwise Cox proportional modeling. The signature exhibited superior accuracy in forecasting the survival outcomes of HCC patients in TCGA, ICGC and the independent clinical cohorts. Patients in high-risk subgroup had significantly increased levels of immune checkpoint molecules including PD-L1, CD276, CTLA4, CXCR4, IL1A, PD-L2, TGFB1, OX40 and CD137, and are therefore more sensitive to immune checkpoint inhibitors (ICIs) treatment. Finally, we first found that overexpression of CLEC1B inhibited the proliferation and migration ability of HuH7 cells.

Conclusions

In summary, the prognostic signature based on TDTRGs and IRGs could effectively help clinicians classify HCC patients for prognosis prediction and individualized immunotherapies.
Distinct clinical features and prognostic factors of hepatitis C virus-associated non-Hodgkin’s lymphoma: a systematic review and meta-analysis
Authors: Zhang Minyue , Gao Fei , Peng Ling , Shen Lijing , Zhao Peng , Ni Beiwen , Hou Jian , Huang Honghui
Published: October 2021

Background

Increasing evidence suggests that hepatitis C virus (HCV) infection is associated with non-Hodgkin’s lymphoma (NHL). However, no clear consensus has been reached about the clinical features and effective treatment of HCV-associated NHL patients. We therefore performed a systematic review and meta-analysis to explore the clinical characteristics and effectiveness of antiviral treatment or rituximab administration among NHL patients with HCV infection.

Methods

Eight electronic databases, including PubMed, OVID, EMBASE, Cochrane Library, ClinicalTrials, WANFANG, CNKI, and VIP, were searched for eligible studies up to July 31, 2021. The hazard ratio (HR) or odds ratio (OR) corresponding to the 95% confidence interval (CI) was calculated to estimate the outcomes. Publication bias was assessed by Egger’s and Begg’s tests. Statistical analysis was performed with RevMan 5.4 software and Stata version 15.

Results

There were 27 shortlisted articles out of a total of 13,368 NHL patients included in the current meta-analysis. Our results demonstrated that NHL patients with HCV infection had a significantly shorter overall survival (OS: HR 1.89; 95% CI 1.42–2.51, P < 0.0001) and progression-free survival (PFS: HR 1.58; 95% CI 1.26–1.98, P < 0.0001), a lower overall response rate (ORR: OR 0.58, 95% CI 0.46–0.73, P < 0.00001) and a higher incidence of hepatic dysfunction during chemotherapy (OR 5.96; 95% CI 2.61–13.62, P < 0.0001) than NHL patients without HCV infection. HCV-positive NHL patients exhibited an advanced disease stage, an elevated level of LDH, a high-intermediate and high IPI/FLIPI risk as well as a higher incidence of spleen and liver involvement. Moreover, antiviral treatment prolonged survival (OS: HR 0.38; 95% CI 0.24–0.60, P < 0.0001), reduced disease progression [PFS/DFS (disease-free survival): HR 0.63; 95% CI 0.46–0.86, P = 0.003] and reinforced the treatment response (ORR: OR 2.62; 95% CI 1.34–5.11, P = 0.005) among the HCV-infected NHL patients. Finally, rituximab administration was associated with a favourable OS, while liver cirrhosis and low levels of albumin predicted a poor OS for HCV-positive NHL patients.

Conclusions

The current study provided compelling evidence about an inferior prognosis and distinct clinical characteristics among HCV-associated NHL patients. Antiviral treatment and rituximab-containing regimens were shown to be efficacious in improving the clinical outcomes of NHL patients with HCV infection.
AL355338 acts as an oncogenic lncRNA by interacting with protein ENO1 to regulate EGFR/AKT pathway in NSCLC
Authors: Hua Qian , Wang Dongliang , Zhao Lin , Hong Zhihui , Ni Kairu , Shi Yizhen , Liu Zengli , Mi Baoming
Published: October 2021

Background

Non-small cell lung cancer (NSCLC) is a malignancy with considerable morbidity and mortality. Abnormal metabolism is a hallmark of cancer; however, the mechanism of glycolysis regulation in NSCLC progression is not completely understood. Recent studies suggest that some dysregulated long non-coding RNAs (lncRNAs) play important roles in tumor metabolic reprogramming.

Methods

To identify glycolysis-associated-lncRNAs in NSCLC, we compared RNA-sequencing results between high 18F-fluorodeoxyglucose (FDG)-uptake NSCLC tissues and paired paratumor tissues. The transcript abundance of AL355338 in 80 pairs of clinical samples was evaluated by quantitative real-time PCR assay and fluorescence in situ hybridization. The biological role of AL355338 on NSCLC cells were evaluated by functional experiments in vitro and in vivo. Moreover, RNA pull-down, mass spectrometry and RNA immunoprecipitation (RIP) assays were used to identify the protein interacted with AL355338. Co-immunoprecipitation, in situ proximity ligation assays and western blotting were applied to define the potential downstream pathways of AL355338.

Results

AL355338 was an upregulated glycolysis-associated lncRNA in NSCLC. Functional assays revealed that AL355338 was critical for promoting aerobic glycolysis and NSCLC progression. Mechanistic investigations showed that AL355338 directly bound with alpha-enolase (ENO1) and enhanced the protein’s stability by modulating its degradation and ubiquitination. A positive correlation was observed between AL355338 and ENO1 in NSCLC, and ENO1 was subsequently confirmed to be responsible for the oncogenic role of AL355338. Furthermore, AL355338 was capable of modulating ENO1/EGFR complex interaction and further activating EGFR-AKT signaling.

Conclusions

This study indicates that AL355338 confers an aggressive phenotype to NSCLC, and targeting it might be an effective therapeutic strategy.
Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia
Authors: Fan Yi , Liao Linxiao , Liu Yajun , Wu Zhenzhen , Wang Chong , Jiang Zhongxing , Wang Shujuan , Liu Yanfang
Published: October 2021

Background

The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML.

Methods

We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis.

Results

In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 109/L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P = 0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients.

Conclusions

Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation.