bluuebunny/crossref_metadata_2025 huggingface dataset:
PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis
Authors: Sohn Eun Jung
Published: June 2022

Background

Ovarian cancer is the most lethal gynecologic disease and is one of the most commonly diagnosed cancers among women worldwide. The phosphatidylinositol 3-kinase (PI3K) family plays an important regulatory role in various cancer signaling pathways, including those involved in ovarian cancer development; however, its exact function remains to be fully understood. We conducted this study to understand the role of P13K in the molecular mechanisms underlying ovarian cancer development.

Methods

To determine the differential gene expression of phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of PI3K, in normal, tumor, and metastatic ovary tissues, TNM plotter analysis was performed. The microarray dataset GSE53759 was downloaded from Gene Expression Omnibus. ROC plotter analysis was conducted to understand the potential of PIK3R3 as a predictive marker for effectiveness of therapy in ovarian cancer. muTarget was used to identify mutations that alter PIK3R3 expression in ovarian cancer. To determine the interacting partners for PIK3R3 in ovarian tissues, the interactome-atlas tool was used. The Kyoto encyclopedia of genes and genomes (KEGG) analysis was conducted to identify the pathways in which these interacting partners were primarily enriched.

Results

PIK3R3 was overexpressed in ovarian and metastatic tumors. Elevated PIK3R3 levels were observed in ovarian cancer stem cells, wherein inhibiting PIK3R3 expression significantly reduced the size of ovarian cancer spheroids. Treatment of ovarian cancer stem cells with PF-04691502 (10 μM), an inhibitor of both PI3K and mTOR kinases, also reduced the size of spheroids and the level of OCT4. PIK3R3 was highly expressed in ovarian cancer with several somatic mutations and was predicted better outcomes in patients undergoing Avastin® chemotherapy using bioinformatic tool. Protein interaction analysis showed that PIK3R3 interacts with 157 genes, including GRB2, EGFR, ERBB3, PTK2, HCK, IGF1R, YES1, and PIK3CA, in the ovary. KEGG enrichment analysis revealed that the interacting partners of PIK3R3 are involved in the ErbB signaling pathway, proteoglycans in cancer, FoxO, prolactin, chemokine, and insulin signaling pathways.

Conclusions

PIK3R3 plays a pivotal role in ovarian cancer development and is therefore a potential candidate for developing novel therapeutic approaches.
Ecological factors and childhood eating behaviours at 5 years of age: findings from the ROLO longitudinal birth cohort study
Authors: Delahunt Anna , Conway Marie C. , O’Brien Eileen C. , Geraghty Aisling A. , O’Keeffe Linda M. , O’Reilly Sharleen L. , McDonnell Ciara M. , Kearney Patricia M. , Mehegan John , McAuliffe Fionnuala M.
Published: June 2022

Background

Individual differences in children eating behaviours have been linked with childhood overweight and obesity. The determinants of childhood eating behaviours are influenced by a complex combination of hereditary and ecological factors. This study examines if key ecological predictors of childhood overweight; maternal socio-economic status (SES), children’s screen time, and childcare arrangements, are associated with eating behaviours in children aged 5-years-old.

Methods

This is secondary, cross-sectional analysis of the ROLO (Randomized COntrol Trial of LOw glycemic diet in pregnancy) study, using data from the 5-year follow-up (n = 306). Weight, height, and body mass index (BMI) were obtained from mothers and children at the 5-year follow-up. Children’s BMI z-scores were calculated. SES was determined using maternal education level and neighborhood deprivation score. Information on children’s screen time and childcare arrangements were collected using lifestyle questionnaires. Children’s eating behaviours were measured using the Children’s Eating Behaviour Questionnaire (CEBQ). Multiple linear regression, adjusted for potential confounders, assessed associations between maternal SES, screen time and children’s eating behaviours. One-way ANOVA, independent sample t-tests and Spearman’s correlation examined childcare exposure and children’s eating behaviour.

Results

Mothers in the lowest SES group had higher BMI and were younger than those in the highest SES group (p =  < 0.001, p = 0.03 respectively). In adjusted analysis, the lowest SES group was associated with a 0.463-point higher mean score for ‘Desire to Drink’ (95% CI = 0.054,0.870, p = 0.027) and higher ‘Slowness to Eat’ (B = 0.388, 95% CI = 0.044,0.733, p = 0.027) when compared with the highest SES group. Screen time (hours) was associated with higher ‘Food Fussiness’ (B = 0.032, 95% CI = 0.014,0.051, p = 0.001). Those who attended childcare had higher scores for ‘Desire to Drink’(p = 0.046). No relationship was observed between longer duration (years) spent in childcare and eating behaviours.

Conclusions

In this cohort, the ecological factors examined had an influence on children’s eating behaviours aged 5-years-old. Our results illustrate the complexity of the relationship between the child’s environment, eating behaviour and children’s body composition. Being aware of the ecological factors that impact the development of eating behaviours, in the pre-school years is vital to promote optimal childhood appetitive traits, thus reducing the risk of issues with excess adiposity long-term.
Challenges and recommendations to improve implementation of phototherapy among neonates in Malawian hospitals
Authors: Kinshella Mai-Lei Woo , Salimu Sangwani , Chiwaya Brandina , Chikoti Felix , Chirambo Lusungu , Mwaungulu Ephrida , Banda Mwai , Hiwa Tamanda , Vidler Marianne , Molyneux Elizabeth M. , Dube Queen , Mfutso-Bengo Joseph , Goldfarb David M. , Kawaza Kondwani , Nyondo-Mipando Alinane Linda
Published: June 2022

Background

Severe neonatal jaundice can result in long term morbidities and mortality when left untreated. Phototherapy is the main-stay intervention for treating moderate jaundice and for prevention of the development of severe jaundice. However, in resource-limited health care settings, phototherapy has been inconsistently used. The objective of this study is to evaluate barriers and facilitators for phototherapy to treat neonatal jaundice at Malawian hospitals.

Methods

We conducted a convergent mixed-method study comprised of a facility assessment and qualitative interviews with healthcare workers and caregivers in southern Malawi. The facility assessment was conducted at three secondary-level hospitals in rural districts. In-depth interviews following a semi-structured topic guide were conducted at a district hospital and a tertiary-level hospital. Interviews were thematically analysed in NVivo 12 software (QSR International, Melbourne, Australia).

Results

The facility assessment found critical gaps in initiating and monitoring phototherapy in all facilities. Based on a total of 31 interviews, participants identified key challenges in diagnosing neonatal jaundice, counselling caregivers, and availability of infrastructure. Participants emphasized the need for transcutaneous bilirubinometers to guide treatment decisions. Caregivers were sometimes fearful of potential harmful effects of phototherapy, which required adequate explanation to mothers and family members in non-medical language. Task shifting and engaging peer support for caregivers with concerns about phototherapy was recommended.

Conclusion

Implementation of a therapeutic intervention is limited if accurate diagnostic tests are unavailable. The scale up of therapeutic interventions, such as phototherapy for neonatal jaundice, requires careful holistic attention to infrastructural needs, supportive services such as laboratory integration as well as trained human resources.
The impact of the euthanasia assessment procedure: a qualitative interview study among adults with psychiatric conditions
Authors: Verhofstadt Monica , Chambaere Kenneth , Pardon Koen , Mortier Freddy , Liégeois Axel , Deliens Luc , Audenaert Kurt
Published: June 2022

Background

Assisted dying for adults with psychiatric conditions (APC) is highly controversial but legally possible in a few countries, including Belgium. Previous research has suggested that the complex euthanasia assessment procedure may cause additional suffering in APC but may also induce positive experiences. This study reports on the impact of the euthanasia assessment procedure as experienced by APC on three counts: 1) their mental state, including death ideation; 2) their treatment trajectory; 3) their social relationships.

Methods

We performed an in-depth qualitative interview study with 16 APC in Flanders, Belgium, who had voiced a euthanasia request between 2016–2020. Thematic coding was used.

Findings

We interviewed 16 APC. Euthanasia assessment procedures brought out a plethora of experiences in APC, both favourable and unfavourable. Whereas thoughts of suicide remain present to a certain extent, being in the assessment procedure allows some APC to reconsider alternatives towards life, and also to attempt new treatment options. However, many APC experience ambivalence about the supposedly inherent desirability and dignity in euthanasia. Worries also surfaced about the rationale behind and effects of involvement of APCs’ social circle, and about the impact it could have on them.

Conclusion

Further research, including other stakeholder perspectives, is recommended with a view to maximising favourable and minimising unfavourable impacts for all involved. In clinical practice attention to these impacts is paramount, and clear communication and management of expectations between physician and patient, seems appropriate to address the many ambivalent experiences that accompany APC during the euthanasia assessment procedure. Policy attention could in this regard go to clarifying certain sources of ambivalence and issues that are insufficiently addressed, such as modalities of relatives’ involvement.
Optimising mothers’ health behaviour after hypertensive disorders of pregnancy: a qualitative study of a postnatal intervention
Authors: Rossiter Chris , Henry Amanda , Roberts Lynne , Brown Mark A. , Gow Megan , Arnott Clare , Salisbury Justine , Ruhotas Annette , Hehir Angela , Denney-Wilson Elizabeth
Published: June 2022

Background

Hypertensive disorders of pregnancy have longer-term implications, increasing women’s lifetime cardiovascular disease risk. The Blood Pressure Postpartum study is a multi-centre randomised three-arm trial of interventions, ranging in intensity and including education and lifestyle coaching, to support women to maintain or adopt healthy eating and physical activity during the first postpartum year. This qualitative sub-study nested within the main trial aimed to investigate whether and how women adopted healthy behaviours after a pregnancy complicated by a hypertensive disorder.

Methods

Semi-structured telephone interviews were recorded, transcribed and analysed thematically, following Braun and Clarke principles. They explored behaviour change among new mothers following their hypertensive pregnancy, and the intervention’s effect on their capacity and motivation to pursue healthy lifestyles.

Results

Thirty-four women from all three trial arms participated at 10–12 months postpartum. The three main themes were 1) Awareness of cardiovascular risk: some did not acknowledge the health risks, whereas others embraced this information. 2) Sources of motivation: while the majority were motivated to make a concerted effort to adapt their health behaviour, motivation often centred on their baby and family rather than their own needs. 3) Sustaining behaviour change with a new baby: women in the more intensive intervention arm demonstrated increased recognition of the importance of reducing cardiovascular health risks, with greater motivation and guidance to change their health behaviour. There was minimal evidence of crossover amongst groups, with women largely accepting their randomised level of intervention and not seeking additional help when randomised to minimal intervention.

Conclusions

Among women participating in an early post-hypertensive disorders of pregnancy randomised controlled trial aimed at improving their cardiovascular disease risk profile, the majority recognised the future health risks and appeared motivated to improve their lifestyle, particularly women in the highest-intensity intervention group. This highlights the importance of structured support to assist women embrace healthy lifestyles especially during the challenges of new parenthood.

Trial registration

The Blood Pressure Postpartum study was prospectively registered as a clinical trial with the Australian New Zealand Clinical Trials Registry (anzctr.org.au) on 13 December 2018 (registration number: ACTRN12618002004246).
Development and validation of a nomogram to predict plastic bronchitis in children with refractory Mycoplasma pneumoniae pneumonia
Authors: Zhao Lihua , Zhang Tongqiang , Cui Xiaojian , Zhao Linsheng , Zheng Jiafeng , Ning Jing , Xu Yongsheng , Cai Chunquan
Published: June 2022

Background

Early identification of plastic bronchitis (PB) is of great importance and may aid in delivering appropriate treatment. This study aimed to develop and validate a nomogram for predicting PB in patients with refractory Mycoplasma pneumoniae pneumonia (RMPP).

Methods

A total of 547 consecutive children with RMPP who underwent fiberoptic bronchoscopy (FOB) intervention from January 2016 to June 2021 were enrolled in this study. Subsequently, 374 RMPP children (PB: 137, without PB: 237) from January 2016 to December 2019 were assigned to the development dataset to construct the nomogram to predict PB and 173 RMPP children from January 2020 to June 2021 were assigned to the validation dataset. The clinical, laboratory and radiological findings were screened using Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression was applied to construct a nomogram. The performance of the nomogram was evaluated by discrimination, calibration and clinical utility. Comparsion of ROC analysis and decision curve analysis (DCA) between nomogram and other models was performed to evaluate the discrimination ability and clinical utility.

Results

The development dataset included 374 patients with a mean age of 6.6 years and 185(49.5%) were men. The validation dataset included 173 patients and the mean age of the dataset was 6.7 years and 86 (49.7%) were men. From 26 potential predictors, LASSO regression identified 6 variables as significant predictive factors to construct the nomogram for predicting PB, including peak body temperature, neutrophil ratio (N%), platelet counts (PLT), interleukin-6 (IL-6), actic dehydrogenase (LDH) and pulmonary atelectasis. The nomogram showed good discrimination, calibration and clinical value. The mean AUC of the nomogram was 0.813 (95% CI 0.769–0.856) in the development dataset and 0.895 (95% CI 0.847–0.943) in the validation dataset. Through calibration plot and Hosmer–Lemeshow test, the predicted probability had a good consistency with actual probability both in the development dataset (P = 0.217) and validation dataset (P = 0.183), and DCA showed good clinical utility. ROC analysis indicated that the nomogram showed better discrimination ability compared with model of peak body temperature + pulmonary atelactsis and another model of N% + PLT + IL-6 + LDH, both in development dataset (AUC 0.813 vs 0.757 vs 0.754) and validation dataset (AUC 0.895 vs 0.789 vs 0.842).

Conclusions

In this study, a nomogram for predicting PB among RMPP patients was developed and validated. It performs well on discrimination ability, calibration ability and clinical value and may have the potential for the early identification of PB that will help physicians take timely intervention and appropriate management.
Smoking cessation by combined medication and counselling: a feasibility study in lung cancer patients
Authors: Reinhardt Christian , Harden Markus , Herrmann-Lingen Christoph , Rittmeyer Achim , Andreas Stefan
Published: June 2022

Purpose

Smoking cessation in patients with diagnosed lung cancer has positive effects on cancer therapy and overall prognosis. Despite this, knowledge on smoking cessation in lung cancer patients is sparse.

Methods

This is an observational single centre, 12-week, prospective, single-arm trial at a tertiary lung cancer centre. Responsive patients were enrolled following confirmed lung cancer diagnosis. Smoking cessation intervention included counselling as well as pharmacotherapy. The primary endpoint was the point prevalence abstinence rate at week 12 based on biochemical verification. Secondary endpoints were the abstinence rate at week 26, quality of life and side effects.

Results

80 patients were enrolled. Mean age was 62.6 ± 7.9 years. Most patients (63%) were treated with chemotherapy or radiochemotherapy. 39 patients used nicotine replacement therapy, 35 varenicline whereas six patients did not use pharmacotherapy. During the study period 13 patients died. Data were available in 72 patients after 12 weeks and 57 patients at week 24. Point prevalence abstinence rates were 37.5% (95% CI 26.4–49.7%) at week 12 and 32.8% (95% CI 21.8–45.4%) at week 26, respectively. Quality of life and side effects were not significantly affected by pharmacotherapy.

Conclusion

In conclusion, our results suggest that smoking cessation is feasible in patients with newly diagnosed lung cancer. The observed abstinence rate is comparable to other patient cohorts. Furthermore, pharmacotherapy in addition to cancer therapy was safe and did not show novel side effects in these seriously ill patients. Thus, smoking cessation should be an integral part of lung cancer treatment.

Trial registration The study was conducted in accordance with good clinical practice standards (GCP) and approved by the local ethics committee (16/3/14), the European PAS registry (EUPAS8748) and the German BfArM (NIS-Studien-Nr. 5508). All patients provided written informed consent before study enrollment.
Sex-specific effects of localized muscle fatigue on upper body kinematics during a repetitive pointing task
Authors: Yang Chen , Côté Julie N.
Published: June 2022

Background

Females are reported to have a higher risk of musculoskeletal disorders than males. Repetitive motions can lead to muscle fatigue, which may play a mediator role in the development of musculoskeletal disorders. However, sex differences in adaptations to localized fatigue at different joints are poorly understood. We examined the sex-specific effects of fatigue location on shoulder, elbow and spinal joint angles, and angular variabilities during a repetitive pointing task.

Methods

Seven males and ten females performed a 30-s standing repetitive pointing task with their right upper limb when they were non-fatigued (NF), elbow-fatigued (EF), shoulder-fatigued (SF) and trunk-fatigued (TF), while trunk and upper body tridimensional kinematic data was recorded. Joint angles and angular variabilities of shoulder, elbow, upper thoracic spine, lower thoracic spine, and lumbar spine were calculated.

Results

Results showed that shoulder angles changed the most after EF in males, but after SF in females. The similarities between sexes were that SF increased the variabilities at upper (lateral flexion: 0.15° greater than NF, rotation: 0.26° greater than all other conditions) and lower thoracic spine (lateral flexion: 0.13° greater than NF, rotation: averagely 0.1° greater than all other condition) in both sexes. TF altered upper thoracic spine variability (0.36° smaller than SF), lower thoracic spine angle (lateral flexion: 3.00° greater than NF, rotation: 1.68° greater than SF), and lumbar angle (averagely 1.8° smaller than all other conditions) in both sexes. However, females had greater lower thoracic spine angle (lateral flexion: 8.3° greater,p = 0.005) as well as greater upper (rotation: 0.53° greater,p = 0.006) and lower thoracic spine (rotation: 0.5° greater,p = 0.007; flexion: 0.6° greater,p = 0.014) angular variabilities than males.

Conclusions

Results suggest that females’ fatigue responses focused on the trunk and spine. Results highlight a few sex differences in adapting to localized muscle fatigue, which may help explain how sex differences in repetitive motion-related injuries differ between joints.
Development and evaluation of a patient education programme for children, adolescents, and young adults with differences of sex development (DSD) and their parents: study protocol of Empower-DSD
Authors: Wiegmann Sabine , Ernst Martina , Ihme Loretta , Wechsung Katja , Kalender Ute , Stöckigt Barbara , Richter-Unruh Annette , Vögler Sander , Hiort Olaf , Jürgensen Martina , Marshall Louise , Menrath Ingo , Schneidewind Julia , Wagner Isabel , Rohayem Julia , Liesenkötter Klaus-Peter , Wabitsch Martin , Fuchs Malaika , Herrmann Gloria , Lutter Henriette , Ernst Gundula , Lehmann Christine , Haase Martina , Roll Stephanie , Schilling Ralph , Keil Thomas , Neumann Uta
Published: June 2022

Background

Differences in sexual development (DSD) are rare diseases, which affect the chromosomal, anatomical or gonadal sex differentiation. Although patient education is recommended as essential in a holistic care approach, standardised programmes are still lacking. The present protocol describes the aims, study design and methods of the Empower-DSD project, which developed an age-adapted multidisciplinary education programme to improve the diagnosis-specific knowledge, skills and empowerment of patients and their parents.

Methods

The new patient education programme was developed for children, adolescents and young adults with congenital adrenal hyperplasia, Turner syndrome, Klinefelter syndrome or XX-/or XY-DSD and their parents. The quantitative and qualitative evaluation methods include standardised questionnaires, semi-structured interviews, and participatory observation. The main outcomes (assessed three and six months after the end of the programme) are health-related quality of life, disease burden, coping, and diagnosis-specific knowledge. The qualitative evaluation examines individual expectations and perceptions of the programme. The results of the quantitative and qualitative evaluation will be triangulated.

Discussion

The study Empower-DSD was designed to reduce knowledge gaps regarding the feasibility, acceptance and effects of standardised patient education programmes for children and youth with DSD and their parents. A modular structured patient education programme with four generic and three diagnosis-specific modules based on the ModuS concept previously established for other chronic diseases was developed. The topics, learning objectives and recommended teaching methods are summarised in the structured curricula, one for each diagnosis and age group. At five study centres, 56 trainers were qualified for the implementation of the training programmes. A total of 336 subjects have been already enrolled in the study. The recruitment will go on until August 2022, the last follow-up survey is scheduled for February 2023. The results will help improve multidisciplinary and integrated care for children and youth with DSD and their families.

Trial registration

German Clinical Trials Register, DRKS00023096. Registered 8 October 2020 – Retrospectively registered.
Analysis of the prevalence, risk factors, and clinical characteristics of osteoporosis in patients with essential hypertension
Authors: Wu Hai-Long , Yang Jie , Wei Yu-Chi , Wang Jian-Yu , Jia Yu-Yan , Li Luan , Zhang Lu , Lu Yan , Luo Zong-Jian , Leng Xiang-Yang
Published: June 2022

Background

The present study investigated the prevalence of osteoporosis (OP) among patients with essential hypertension (EH) in the Changchun community and analysed the correlation between EH and OP.

Methods

The study included 425 subjects with EH and 425 age- and sex-matched healthy controls. Bone mineral density (BMD) and serum creatinine (CR) levels were measured, and the subjects' current EH and OP statuses were surveyed to analyse the correlation between EH and OP.

Results

The EH group exhibited lower BMD and a higher rate of having OP than the control group, and this difference was statistically significant (p < 0.05). A significant sex difference in the BMD T-score was observed among the subjects (male: − 1.19 ± 1.55, female: − 1.70 ± 1.34). In both the EH group and the control group, the rate of having OP in females was greater than that in males. However, the OP prevalence among subjects with EH varied significantly by age, body weight, fracture history, nocturnal urination frequency, depression and anxiety status, duration of hypertension, and antihypertensive medication use (p < 0.05). Two-way analysis of variance suggested an effect of the interaction between different EH statuses and bone mass conditions on the serum CR values (F = 3.584, p = 0.028, bias η2 = 0.008).

Conclusions

The prevalence of OP and low BMD were significantly higher among subjects with EH than among healthy controls. Additionally, the findings indicate that age, weight, fracture history, nocturnal urination frequency, depression and anxiety, duration of hypertension and antihypertensive drug use may be correlated to having OP in EH subjects, requiring further studies. Moreover, serum CR levels in subjects with different bone mass profiles were strongly influenced by the presence or absence of EH, and the serum CR levels differed significantly with the interaction of these two factors.
Third-party toothbrushing is associated with a positive patient experience: randomized, single-blind, patient-centered analysis
Authors: Barbe Anna Greta , Al-Barwari Aya , Weik Ulrike , Noack Michael J. , Deinzer Renate
Published: June 2022

Background

As the need for care increases with higher age, so does the need for assistance with oral hygiene. A recent study analyzed the clinical effectiveness of oral hygiene assistance provided by caregivers. The current secondary analysis of this study aimed to assess pleasant and unpleasant perceptions of patients while being brushed and to investigate whether these perceptions depend on the qualification of the person brushing and the type of toothbrush used (manual vs. powered).

Methods

First, a qualitative study was conducted. This aimed at developing the questionnaire. Items were extracted on the basis of qualitative interviews with a sample of 6. A delphi process ensured the content validity of the final instrument. The main study comprised 39 periodontitis patients with reduced oral hygiene capability randomized to one of four groups: brushing carried out by trained laypeople or dental professionals, each using a manual or powered toothbrush at three different time points during anti-infective periodontal therapy. Patient perceptions of the third-party toothbrushing were assessed immediately after brushing.

Results

Patients reported mainly positive feelings regarding being brushed by a third person and the interaction with this person during brushing. Neither the professional background of the brushing person nor the type of brush had a significant influence on pleasant and unpleasant perceptions (all F < 3.30, all p > 0.07, all η2 < 0.10).

Conclusions

Patient perceptions of third-party toothbrushing are mainly positive regarding wellbeing and interactions with the toothbrushing person, and do not depend on the qualification of the brushing person or the toothbrush used (manual versus powered).

Trial registration

https://www.germanctr.de, No. DRKS00018779 (04/11/2019).
Female homicides and femicides in Ecuador: a nationwide ecological analysis from 2001 to 2017
Authors: Ortiz-Prado Esteban , Villagran Paola , Martinez-Abarca Ana Lucia , Henriquez-Trujillo Aquiles R. , Simbaña-Rivera Katherine , Gómez-BarrenoDiaz Lenin Ana M. , Moyano Carla E. , Arcos-Valle Vanessa , Miño Maria Dolores , Morgan Sara A.
Published: June 2022

Background

Gender–based violence is a major public health concern arising from the structural discrimination of women and girls. In 2014, Ecuador criminalized acts of femicide in response to a growing crisis across the region. As no epidemiological studies on the state of female homicides and femicides have been published, we estimated patterns of female homicides and femicides nationally and the burden through economic cost per years of life lost, between 2001 and 2017.

Methods

Using aggregated data from the National Institute of Census and Statistics and police records we estimated the annual mortality rates, cumulative incidence and prevalence odds ratios for female homicides and femicides, from 2001 to 2017. The impact of aggressions, assaults and violence on years of life lost due to premature mortality was estimated using the Human Capital method.

Results

Over the period, at least 3236 cases of female homicides and femicides were reported. The highest murder rate occurred in the province of Sucumbíos (6.5 per 100,000) and in the Putumayo canton (12.5 per 100,000). The most common way to murder their victims was using firearms (38%). The highest odds ratio was estimated for women aged between 25 and 29, at 4.5 (3.9–5.1), of primary school attainment at 17.2 (14.6–20.3) and of Afro-Ecuadoran descent 18.1 (10.5–30.9). Female homicide-related costs reached, on average, $35 million per year and more than $500 million lost from 2001 to 2017.

Conclusions

The high rates, distribution and cost indicate that investments are urgently needed to address the structural causes and reduce the impact of female homicides and femicides in Ecuador; thereby protecting the livelihood and well-being of their women and girls.
“Why don’t I look like her?” How adolescent girls view social media and its connection to body image
Authors: Papageorgiou Alana , Fisher Colleen , Cross Donna
Published: June 2022

Background

Adolescent girls appear more vulnerable to experiencing mental health difficulties from social media use than boys. The presence of sexualized images online is thought to contribute, through increasing body dissatisfaction among adolescent girls. Sexual objectification through images may reinforce to adolescent girls that their value is based on their appearance. This study explored how sexualized images typically found on social media might influence adolescent girls’ mental health, in positive and/or negative ways.

Methods

In-depth interviews were conducted with girls aged 14–17 years (n = 24) in Perth, Western Australia. Data were analyzed using thematic analysis.

Results

Participants identified body image as a major concern, reporting negative appearance comparisons when viewing images on social media. Appearance comparisons were perceived to exacerbate adolescent girls’ appearance-based concerns. Comparisons also influenced adolescent girls’ efforts to change their appearance and seek validation on social media. The importance of awareness and education from a younger age about social media and its influence on body image was emphasized, as was the need for strategies to promote positive body image and counteract negative body image.

Conclusion

The findings of this study have important implications for professionals working with adolescent girls and for the development of health promotion programs addressing social media use and body image concerns.
Development of a questionnaire to measure teachers’ student-centred perspectives based on the Onion Model
Authors: Leatemia Lukas Daniel , van Merrienboer Jeroen J. G. , Susilo Astrid Pratidina
Published: June 2022

Background

Teachers with a teacher-centred perspective have difficulties applying student-centred approaches in Problem Based Learning (PBL) because they are inclined to show teacher-centred behaviours. The six aspects explained in Korthagen’s Onion Model (environment, behaviour, competencies, beliefs, identity, and mission) are assumed to contribute to teachers’ perspectives, showing that both the environment and personal characteristics influence behaviours. For teachers to function properly in PBL, those six aspects should reflect a student-centred perspective. Previous instruments to measure teaching perspectives focused on only a few of these relevant aspects. Therefore, we developed the Student-Centred Perspective of Teachers (SCPT) questionnaire with subscales for each aspect in the Onion Model. This study aimed to provide evidence for its internal and external validity.

Methods

The SCPT was distributed in a survey to 795 teachers from 20 medical schools. For the internal validation, Confirmatory Factor Analysis was performed to analyse theoretical fit model validation, convergent validation, and discriminant validation. For the external validation, teachers’ perspective scores were compared among three groups of amount of PBL training using Analysis of Variance (ANOVA) and post-hoc Least Significant Difference (LSD) tests. The p-value for all tests was set at .05.

Results

A total of 543 out of 795 teachers (68.3%) participated. Confirmatory Factor Analysis showed the evidence of the SCPT’s internal validation with acceptable fit for the six subscales measured by 19 items and the following Composite Reliability scores: environment (.72), behaviour (.74), competencies (.63), beliefs (.55), identity (.76), and mission (.60). All items’ factors loadings reached a good standard (.5 or greater). Only the environment subscale had the Average Variance Extracted (AVE) score higher than .5 and the Maximum Shared Variance score lower than the AVE score. ANOVA and Post-hoc LSD tests showed that teachers who participated in more PBL training showed significantly higher student-centred perspectives, providing evidence for external validity.

Conclusion

The SCPT is a reliable and valid instrument to measure teaching perspectives. Identifying aspects that do not represent the adoption of a student-centred perspective may provide valuable input for faculty development in the context of PBL.
Investigating the characteristics of genes and variants associated with self-reported hearing difficulty in older adults in the UK Biobank
Authors: Lewis Morag A. , Schulte Bradley A. , Dubno Judy R. , Steel Karen P.
Published: June 2022

Background

Age-related hearing loss is a common, heterogeneous disease with a strong genetic component. More than 100 loci have been reported to be involved in human hearing impairment to date, but most of the genes underlying human adult-onset hearing loss remain unknown. Most genetic studies have focussed on very rare variants (such as family studies and patient cohort screens) or very common variants (genome-wide association studies). However, the contribution of variants present in the human population at intermediate frequencies is hard to quantify using these methods, and as a result, the landscape of variation associated with adult-onset hearing loss remains largely unknown.

Results

Here we present a study based on exome sequencing and self-reported hearing difficulty in the UK Biobank, a large-scale biomedical database. We have carried out variant load analyses using different minor allele frequency and impact filters, and compared the resulting gene lists to a manually curated list of nearly 700 genes known to be involved in hearing in humans and/or mice. An allele frequency cutoff of 0.1, combined with a high predicted variant impact, was found to be the most effective filter setting for our analysis. We also found that separating the participants by sex produced markedly different gene lists. The gene lists obtained were investigated using gene ontology annotation, functional prioritisation and expression analysis, and this identified good candidates for further study.

Conclusions

Our results suggest that relatively common as well as rare variants with a high predicted impact contribute to age-related hearing impairment and that the genetic contributions to adult hearing difficulty may differ between the sexes. Our manually curated list of deafness genes is a useful resource for candidate gene prioritisation in hearing loss.
Metabolomics profile in acute respiratory distress syndrome by nuclear magnetic resonance spectroscopy in patients with community-acquired pneumonia
Authors: Yan Yongqin , Chen Jianuo , Liang Qian , Zheng Hong , Ye Yiru , Nan Wengang , Zhang Xi , Gao Hongchang , Li Yuping
Published: June 2022

Background

Acute respiratory distress syndrome (ARDS) is a challenging clinical problem. Discovering the potential metabolic alterations underlying the ARDS is important to identify novel therapeutic target and improve the prognosis. Serum and urine metabolites can reflect systemic and local changes and could help understanding metabolic characterization of community-acquired pneumonia (CAP) with ARDS.

Methods

Clinical data of patients with suspected CAP at the First Affiliated Hospital of Wenzhou Medical University were collected from May 2020 to February 2021. Consecutive patients with CAP were enrolled and divided into two groups: CAP with and without ARDS groups.1H nuclear magnetic resonance-based metabolomics analyses of serum and urine samples were performed before and after treatment in CAP with ARDS (n = 43) and CAP without ARDS (n = 45) groups. Differences metabolites were identifed in CAP with ARDS. Furthermore, the receiver operating characteristic (ROC) curve was utilized to identify panels of significant metabolites for evaluating therapeutic effects on CAP with ARDS. The correlation heatmap was analyzed to further display the relationship between metabolites and clinical characteristics.

Results

A total of 20 and 42 metabolites were identified in the serum and urine samples, respectively. Serum metabolic changes were mainly involved in energy, lipid, and amino acid metabolisms, while urine metabolic changes were mainly involved in energy metabolism. Elevated levels of serum 3-hydroxybutyrate, lactate, acetone, acetoacetate, and decreased levels of serum leucine, choline, and urine creatine and creatinine were detected in CAP with ARDS relative to CAP without ARDS. Serum metabolites 3-hydroxybutyrate, acetone, acetoacetate, citrate, choline and urine metabolite 1-methylnicotinamide were identified as a potential biomarkers for assessing therapeutic effects on CAP with ARDS, and with AUCs of 0.866 and 0.795, respectively. Moreover, the ROC curve analysis revealed that combined characteristic serum and urine metabolites exhibited a better classification system for assessing therapeutic effects on CAP with ARDS, with a AUC value of 0.952. In addition, differential metabolites strongly correlated with clinical parameters in patients with CAP with ARDS.

Conclusions

Serum- and urine-based metabolomics analyses identified characteristic metabolic alterations in CAP with ARDS and might provide promising circulatory markers for evaluating therapeutic effects on CAP with ARDS.
Stakeholder perceptions on the deployment of multiple first-line therapies for uncomplicated malaria: a qualitative study in the health district of Kaya, Burkina Faso
Authors: Hien Denise , Kaboré Jean Moise Tanga , Siribié Mohamadou , Soulama Issiaka , Barry Nouhoun , Baguiya Adama , Tiono Alfred Bewendtaoré , Tchouatieu André-Marie , Sirima Sodiomon Bienvenu
Published: June 2022

Background

In Burkina Faso, malaria remains the first cause of medical consultation and hospitalization in health centres. First-line case management of malaria in the country’s health facilities is based on the use of artemisinin-based combination therapy (ACT). To optimize the use of these anti-malarial drugs in the perspective of mitigating the emergence of artemisinin resistance, which is a serious threat to malaria control and elimination, a pilot programme using multiple first-line therapies (MFTs) [three artemisinin-based combinations—pyronaridine–artesunate, dihydroartemisinin–piperaquine and artemether-lumefantrine] has been designed for implementation. As the success of this MFT pilot programme depends on the perceptions of key stakeholders in the health system and community members, the study aimed to assess their perceptions on the implementation of this strategy.

Methods

Semi-structured interviews, including 27 individual in-depth interviews and 41 focus groups discussions, were conducted with key stakeholders including malaria control policymakers and implementers, health system managers, health workers and community members. Volunteers from targets stakeholder groups were randomly selected. All interviews were recorded, transcribed and translated. Content analysis was performed using the qualitative software programme QDA Miner.

Results

The interviews revealed a positive perception of stakeholders on the implementation of the planned MFT programme. They saw the strategy as an opportunity to strengthen the supply of anti-malarial drugs and improve the management of fever and malaria. However, due to lack of experience with the products, health workers and care givers expressed some reservations about the effectiveness and side-effect profiles of the two anti-malarial drugs included as first-line therapy in the MFT programme (pyronaridine–artesunate, dihydroartemisinin–piperaquine). Questions were raised about the appropriateness of segmenting the population into three groups and assigning a specific drug to each group.

Conclusion

The adherence of both populations and key stakeholders to the MFT implementation strategy will likely depend on the efficacy of the proposed drugs, the absence of, or low frequency of, side-effects, the cost of drugs and availability of the different combinations.
Global research trends of immunotherapy and biotherapy for inflammatory bowel disease: a bibliometric analysis from 2002 to 2021
Authors: Xiong Jia-Qi , Fu Yun-Feng , Qiu Jian-Hao , Liao Wang-Di , Luo Ling-Yu , Chen Si-Hai
Published: June 2022

Background

It is known that inflammatory bowel disease is the result of a defective immune system, and immunotherapy and biological therapy have gradually become important means to treat it. This paper focused on the bibliometric statistical analysis of the current research progress to summarize the research status of this field and analyze the research trends in recent years.

Methods

Two visualization tools, CiteSpace and VOSviewer, were used to explore the data of journals, institutions, countries/regions, authors, references, and keywords for the literature included in the Web of Science Core Collection from January 1, 2002, to December 31, 2021.

Results

A total of 312 papers were published in 120 journals by 603 institutions from 40 countries/regions, with 9463 co-cited references. The United States has the most publications with the highest total citations in the world. Inflammatory Bowel Diseases published the maximum number of papers, and Gastroenterology devoted the most co-citations to immunotherapy and biological therapy for IBD. In addition, we found that the studies before 2009 mostly focused on clinical trials while researchers have paid more attention to clinical management in therapy for IBD since 2009. Combination therapy and management of the treatment for the disease have become research hotspots.

Conclusion

The focus of immunotherapy and biotherapy for IBD has shifted from clinical trials to the management of the risks and benefits of immunotherapy.
Tumor-suppressive MEG3 induces microRNA-493-5p expression to reduce arabinocytosine chemoresistance of acute myeloid leukemia cells by downregulating the METTL3/MYC axis
Authors: Wang Airong , Chen Yufei , Shi Luyao , Li Mengya , Li Lingling , Wang Shujuan , Wang Chong
Published: June 2022

Background

Chemoresistance serves as a huge obstacle for acute myeloid leukemia (AML) patients. To counteract the chemoresistance in AML cells, we discussed the role of maternally expressed gene 3 (MEG3) in arabinocytosine (AraC) chemoresistance in AML cells.

Methods

MEG3, microRNA (miR)-493-5p, methyltransferase-like 3 (METTL3) and MYC expression in AML cells was determined and then their interactions were also analyzed. Then, the viability and apoptosis of AML cells were determined through loss- and gain- function assay. The level of m6A modification in AML cells was examined. AML mouse models were also established to validate the potential roles of MEG3.

Results

MEG3 and miR-493-5p were downregulated in AML cells, and they were lower in resistant cells than in parental cells. MEG3 led to elevated expression of miR-493-5p which targeted METTL3. METTL3 increased expression of MYC by promoting its m6A levels. Overexpression of MEG3 and miR-493-5p or knockdown of METTL3 inhibited HL-60 and Molm13 cell proliferation and promoted their apoptosis. Overexpressed MEG3 induced heightened sensitivity of AML cells to AraC. However, the suppression of miR-493-5p reversed the effects of overexpressed MEG3 on AML cells.

Conclusions

Collectively, MEG3 could upregulate miR-493-5p expression and suppress the METTL3/MYC axis through MYC m6A methylation, by which MEG3 promoted the chemosensitivity of AML cells.
Inhibition of autophagy by chloroquine prevents resistance to PI3K/AKT inhibitors and potentiates their antitumor effect in combination with paclitaxel in triple negative breast cancer models
Authors: Cocco Stefania , Leone Alessandra , Roca Maria Serena , Lombardi Rita , Piezzo Michela , Caputo Roberta , Ciardiello Chiara , Costantini Susan , Bruzzese Francesca , Sisalli Maria José , Budillon Alfredo , De Laurentiis Michelino
Published: June 2022

Background

Triple negative breast cancer (TNBC) is an aggressive disease characterized by high risk of relapse and development of resistance to different chemotherapy agents. Several targeted therapies have been investigated in TNBC with modest results in clinical trials. Among these, PI3K/AKT inhibitors have been evaluated in addition to standard therapies, yielding conflicting results and making attempts on elucidating inherent mechanisms of resistance of great interest. Increasing evidences suggest that PI3K/AKT inhibitors can induce autophagy in different cancers. Autophagy represents a supposed mechanism of drug-resistance in aggressive tumors, like TNBC. We, therefore, investigated if two PI3K/AKT inhibitors, ipatasertib and taselisib, could induce autophagy in breast cancer models, and whether chloroquine (CQ), a well known autophagy inhibitor, could potentiate ipatasertib and taselisib anti-cancer effect in combination with conventional chemotherapy.

Methods

The induction of autophagy after ipatasertib and taselisib treatment was evaluated in MDAMB231, MDAM468, MCF7, SKBR3 and MDAB361 breast cancer cell lines by assaying LC3-I conversion to LC3-II through immunoblotting and immunofluorescence. Other autophagy-markers as p62/SQSTM1 and ATG5 were evaluated by immunoblotting. Synergistic antiproliferative effect of double and triple combinations of ipatasertib/taselisib plus CQ and/or paclitaxel were evaluated by SRB assay and clonogenic assay. Anti-apoptotic effect of double combination of ipatasertib/taselisib plus CQ was evaluated by increased cleaved-PARP by immunoblot and by Annexin V- flow cytometric analysis. In vivo experiments were performed on xenograft model of MDAMB231 in NOD/SCID mice.

Results

Our results suggested that ipatasertib and taselisib induce increased autophagy signaling in different breast cancer models. This effect was particularly evident in PI3K/AKT resistant TNBC cells, where the inhibition of autophagy by CQ potentiates the therapeutic effect of PI3K/AKT inhibitors in vitro and in vivo TNBC models, synergizing with taxane-based chemotherapy.

Conclusion

These data suggest that inhibition of authophagy with CQ could overcome mechanism of drug resistance to PI3K/AKT inhibitors plus paclitaxel in TNBC making the evaluation of such combinations in clinical trials warranted.