bluuebunny/crossref_metadata_2025 huggingface dataset:
Additional prognostic value of toe-brachial index beyond ankle-brachial index in hemodialysis patients
Authors: Hishida Manabu , Imaizumi Takahiro , Menez Steven , Okazaki Masaki , Akiyama Shin’ichi , Kasuga Hirotake , Ishigami Junichi , Maruyama Shoichi , Matsushita Kunihiro
Published: August 2020

Background

Ankle-brachial index (ABI), the first-line diagnostic test for peripheral artery disease, can be falsely elevated when ankle arteries are incompressible, showing a J-shaped association with mortality. In this situation, toe-brachial index (TBI) is the recommended test. However, whether TBI provides additional prognostic information beyond ABI in patients on hemodialysis is unknown.

Methods

In this retrospective cohort study of 247 Japanese prevalent hemodialysis patients (mean age 66.8 [SD 11.6] years), we evaluated mortality (116 deaths over a median follow-up of 5.2 years) related to quartiles of ABI and TBI, as well as three categories of low ABI (≤0.9), normal/high ABI (> 0.9) + low TBI (≤0.6), and normal/high ABI + normal TBI (> 0.6) using multivariable Cox models.

Results

ABI showed a J-shaped association with mortality (adjusted hazard ratio 2.72 [95% CI, 1.52–4.88] in the lowest quartile and 1.59 [95% CI, 0.87–2.90] in the highest quartile vs. the second highest). Lower TBI showed a potentially dose-response association with mortality (e.g., adjusted hazard ratios 2.63 [95% CI, 1.36–5.12] and 2.89 [95% CI, 1.49–5.61] in the lowest two quartiles vs. the highest). When three categories by both ABI and TBI were analyzed, those with low ABI (≤0.9) experienced the highest risk followed by normal/high ABI (> 0.9) + low TBI (≤0.6). Among patients with normal/high ABI (> 0.9), the increased mortality risk in individuals with low TBI (≤0.6) compared to those with normal TBI (> 0.6) were significant (adjusted hazard ratio 1.84 [95% CI, 1.12–3.02]).

Conclusions

Lower TBI was independently associated with mortality in patients on hemodialysis and has the potential to classify mortality risk in patients with normal/high ABI. Our results support the importance of evaluating TBI in addition to ABI in this clinical population.
Microvascular inflammation is a risk factor in kidney transplant recipients with very late conversion from calcineurin inhibitor-based regimens to belatacept
Authors: Choi Mira , Bachmann Friederike , Wu Kaiyin , Lachmann Nils , Schmidt Danilo , Brakemeier Susanne , Duerr Michael , Kahl Andreas , Eckardt Kai-Uwe , Budde Klemens , Nickel Peter
Published: August 2020

Background

In de novo kidney transplant recipients (KTR) treatment with belatacept has been established as a comparable option as maintenance immunosuppression, preferably as a strategy to convert from calcineurin inhibitor (CNI)- to belatacept-based immunosuppression. Switch to belatacept demonstrated improved renal function in patients with CNI-induced nephrotoxicity, but risk of transplant rejection and the development of donor-specific antibodies (DSA) are still a matter of debate. Only few data are available in patients at increased immunological risk and late after transplantation.

Methods

We analyzed 30 long-term KTR (including 2 combined pancreas-KTR) converted from CNI to belatacept > 60 months after transplantation with moderate to severe graft dysfunction (GFR ≤ 45 mL/min). Biopsies were classified according to the Banff 2015 criteria. Group differences were assessed in a univariate analysis using Mann Whitney U or Chi square test, respectively. Multivariate analysis of risk factors for treatment failure was performed using a binary logistic regression model including significant predictors from univariate analysis. Fifty-six KTR matched for donor and recipient characteristics were used as a control cohort remaining under CNI-treatment.

Results

Patient survival in belatacept cohort at 12/24 months was 96.7%/90%, overall graft survival was 76.7 and 60.0%, while graft survival censored for death was 79.3%/66.7%. In patients with functioning grafts, median GFR improved from 22.5 mL/min to 24.5 mL/min at 24 months. Positivity for DSA at conversion was 46.7%. From univariate analysis of risk factors for graft loss, GFR < 25 mL/min (p = 0.042) and Banff microvascular inflammation (MVI) sum score ≥ 2 (p = 0.023) at conversion were significant at 24 months. In the analysis of risk factors for treatment failure, a MVI sum score ≥ 2 was significant univariately (p = 0.023) and in a bivariate (p = 0.037) logistic regression at 12 months. DSA-positivity was neither associated with graft loss nor treatment failure. The control cohort had comparable graft survival outcomes at 24 months, albeit without increase of mean GFR in patients with functioning grafts (ΔGFR of − 3.6 ± 8.5 mL/min).

Conclusion

Rescue therapy with conversion to belatacept is feasible in patients with worsening renal function, even many years after transplantation. The benefit in patients with MVI and severe GFR impairment remains to be investigated.
Design characteristics of studies on medical practice variation of caesarean section rates: a scoping review
Authors: Vink Maarten D H , de Bekker Piet J G M , Koolman Xander , van Tulder Maurits W , de Vries Ralph , Mol Ben Willem J , van der Hijden Eric J E
Published: August 2020

Background

Medical practice variation in caesarean section rates is the most studied type of practice variation in the field of obstetrics and gynaecology. This has not resulted in increased homogeneity of treatment between geographic areas or healthcare providers. Our study aim was to evaluate whether current study designs on medical practice variation of caesarean section rates were optimized to identify the unwarranted share of practice variation and could contribute to the reduction of unwarranted practice variation by meeting criteria for audit and feedback.

Methods

We searched PubMed, Embase, EBSCO/CINAHL and Wiley/Cochrane Library from inception to March 24th, 2020. Studies that compared the rate of caesarean sections between individuals, institutions or geographic areas were included. Study design was assessed on: selection procedure of study population, data source, case-mix correction, patient preference, aggregation level of analysis, maternal and neonatal outcome, and determinants (professional and organizational characteristics).

Results

A total of 284 studies were included. Most studies (64%) measured the caesarean section rate in the entire study population instead of using a sample (30%). (National) databases were most often used as information source (57%). Case-mix correction was performed in 87 studies (31%). The Robson classification was used in 20% of the studies following its endorsement by the WHO in 2015. The most common levels of aggregation were hospital level (35%) and grouped hospitals (35%) e.g. private versus public. The percentage of studies that assessed the relationship between variation in caesarean section rates and maternal outcome was 9%, neonatal outcome 19%, determinants (professional and organizational characteristics) 21% and patient preference 2%.

Conclusions

Study designs of practice variation in caesarean sections varied considerably, raising questions about their appropriateness. Studies focused on measuring practice variation, rather than contributing to the reduction of unwarranted practice variation. Future studies should correct for differences in patient characteristics (case-mix) and patient preference to identify unwarranted practice variation. Practice variation studies could be used for audit and feedback if results are presented at lower levels of aggregation, and appeal to intrinsic motivation of physicians, for example by including the health effects on mother and child.
Pneumonitis after radiotherapy for lung cancer (PARALUC): an interventional study to create a symptom-based scoring system for identification of patients developing radiation pneumonitis
Authors: Rades Dirk , Werner Elisa Marie , Glatzel Esther , Eggert Marie-Christine , Olbrich Denise , Tvilsted Soeren , Bohnet Sabine
Published: August 2020

Background

Pneumonitis is a possible side effect of radiotherapy for lung cancer. Since it can occur up to several months following treatment, symptoms may not be associated with previous radiotherapy, and pneumonitis can become severe before diagnosed. This study aimed to develop a symptom-based scoring system to contribute to earlier detection of radiation pneumonitis requiring medical intervention (grade ≥ 2).

Methods

Patients irradiated for lung cancer complete a paper-based questionnaire (symptom-based score) during and up to 24 weeks following radiotherapy. Patients rate symptoms potentially associated with pneumonitis, and scoring points are assigned to severity of these symptoms. Sum scores are used to identify radiation pneumonitis. If radiation pneumonitis is suspected, patients undergo standard diagnostic procedures. If grade ≥ 2 pneumonitis is confirmed, medical intervention is indicated. The discriminative power of the score will be assessed by calculating the area under the receiver operating characteristic curve (AUC). If statistical significance of the AUC is reached, the optimal sum score to predict radiation pneumonitis will be established, which is defined as a cut-off value with sensitivity ≥90% and specificity ≥80%. Assuming a ratio between patients without and with pneumonitis of 3.63, a sample size of 93 patients is required in the full analysis set to yield statistical significance at the level of 5% with a power of 90% if the AUC under the alternative hypothesis is at least 0.9. Considering potential drop-outs, 98 patients should be recruited. If > 20% of patients are not satisfied with the score, modification is required. If the dissatisfaction rate is > 40%, the score is considered not useful. In 10 patients, functionality of a mobile application will be tested in addition to the paper-based questionnaire.

Discussion

If an optimal cut-off score resulting in sufficiently high sensitivity and specificity can be identified and the development of a symptom-based scoring system is successful, this tool will contribute to better identification of patients experiencing pneumonitis after radiotherapy for lung cancer.

Trial registration

Clinicaltrials.gov (NCT04335409); registered on 2nd of April, 2020.
Long-term sexual functioning in germ-cell tumor survivors
Authors: Chovanec M. , Vasilkova L. , Petrikova L. , Obertova J. , Palacka P. , Rejlekova K. , Sycova-Mila Z. , Kalavska K. , Svetlovska D. , Mladosievicova B. , Mardiak J. , Mego M.
Published: August 2020

Background

Survivors of germ-cell tumors (GCT) may suffer from long-term adverse consequences. Our study was conducted to assess a long-term sexual functioning in GCT survivors.

Methods

GCT survivors (N = 170) from the National Cancer Institute in Slovakia completed a Sexual Function Questionnaire that was modified from PROMIS Sexual Function and Satisfaction Questionnaire 9-year median follow up (range 5–32) as a primary exploratory aim. Study groups consisted of 17 survivors (10%) who had active surveillance (AS, controls), and 153 (90%) survivors who received treatment beyond orchiectomy (Tx), including cisplatin-based chemotherapy (CT, N = 132; 78%), radiotherapy to the retroperitoneal lymph nodes (RT, N = 12; 7%) or both (CTRT, N = 9; 5%).

Results

In univariate analysis, treatment of any type resulted in difficulty to maintain erection during sexual intercourse compared to patients treated with AS (P = 0.04). Survivors who received CTRT had lower ability to achieve orgasm during sexual activities (P = 0.04) and they reported disappointment with their overall quality of sex life (P = 0.002). The number of attempts to initiate sexual intercourse did not differ. Sexual relationships caused none or mild anxiety and the desire to be sexually active was higher after CTRT (P = 0.05). Multivariable analysis confirmed that orgasmic dysfunction after ≥400 mg/m2 of cisplatin and issues in maintaining erection after Tx were independent of retroperitoneal lymph-node dissection (P = 0.03 and P = 0.04, respectively). Survivors were disappointed with the quality of sex life and had stronger desire to be sexually active independent of age, (P = 0.01 and P = 0.05, respectively).

Conclusions

This study identified an impairment in sexual function may represent an issue for long-term GCT survivors. Treatment with chemotherapy plus radiotherapy were associated with disappointment and stronger sexual desire, while a higher cumulative dose of cisplatin may be responsible for orgasmic dysfunction.
Food groups intake in relation to stunting among exceptional children
Authors: Nachvak Seyyed Mostafa , Sadeghi Omid , Moradi Shima , Esmailzadeh Ahmad , Mostafai Roghayeh
Published: August 2020

Background

Although several studies have examined the link between different food groups intake and stunting among children, no study, to our knowledge, was done on exceptional children. The aim of this study was assessed the association of dietary intake and stunting in Iranian exceptional children.

Methods

This cross-sectional study was conducted on 470 exceptional children (226 mentally retarded, 182 deaf and 62 blind children), aged 5–15 years. Height was measured using standard tool. Stunting was defined as height-for-age z-score of <-1. A validated dietary habit questionnaire was applied to assess dietary intakes.

Results

Mean age of children was 10.02 ± 2.04 years. Stunting was prevalent among 50.6% of children. Compared with children in the lowest category of dairy consumption, those in the highest category had lower odds of stunting. This association remained significant even after adjusting for covariates (OR: 0.50, 95% CI: 0.29–0.87). In addition, moderate consumption of egg (1–3 time/wk) was inversely associated with stunting either before or after controlling for potential confounders (OR: 0.36, 95% CI: 0.21–0.64). Such finding was also seen among mentally retarded children (OR: 0.38, 95% CI: 0.16–0.89). No other significant association was seen between intakes of other food groups (including meat, fruits and vegetables) and stunting.

Conclusions

We found that higher intake of dairy products and egg was associated with lower risk of stunting. However, intakes of other food groups including meat, fruits and vegetables were not significantly related to stunting.
Psychiatric comorbidity in individuals with bullous pemphigoid and all bullous disorders in the Danish national registers
Authors: Rania Marianna , Petersen Liselotte Vogdrup , Benros Michael Eriksen , Liu Zhi , Diaz Luis , Bulik Cynthia M.
Published: August 2020

Background

Bullous pemphigoid (BP) is an autoimmune blistering skin disease that takes a profound physical and mental toll on those affected. The aim of the study was to investigate the bidirectional association between BP and all bullous disorders (ABD) with a broad array of psychiatric disorders, exploring the influence of prescribed medications.

Methods

This nationwide, register-based cohort study encompassed 6,470,450 individuals born in Denmark and alive from 1994 to 2016. The hazard ratios (HRs) of a subsequent psychiatric disorder in patients with BP/ABD and the reverse exposure and outcome were evaluated.

Results

Several psychiatric disorders were associated with increased risk of subsequent BP (4.18-fold for intellectual disorders, 2.32-fold for substance use disorders, 2.01-fold for schizophrenia and personality disorders, 1.92–1.85-1.49-fold increased risk for organic disorders, neurotic and mood disorders), independent of psychiatric medications. The association between BP and subsequent psychiatric disorders was not significant after adjusting for BP medications, except for organic disorders (HR 1.27, CI 1.04–1.54). Similar results emerged with ABD.

Conclusion

Psychiatric disorders increase the risk of a subsequent diagnosis of BP/ABD independent of medications, whereas medications used for the treatment of BP/ABD appear to account for the subsequent onset of psychiatric disorders. Clinically, an integrated approach attending to both dermatological and psychiatric symptoms is recommended, and dermatologists should remain vigilant for early symptoms of psychiatric disorders to decrease mental health comorbidity.
Psychosocial family interventions for relatives of people living with psychotic disorders in the Arab world: systematic review
Authors: Al-Sawafi Aziza , Lovell Karina , Renwick Laoise , Husain Nusrat
Published: August 2020

Background

Family interventions in schizophrenia are evidence based and have been adapted to different cultural settings to improve their effectiveness and acceptability. The Arab world has a unique set of socio-cultural norms and values that cannot be ignored when developing or implementing such interventions. There is a lack of research on the feasibility of delivering family interventions for schizophrenia in the Arab region. The aim of this review is to synthesise the available evidence about culturally-adapted psychosocial family interventions in the Arab world. The review identifies the content and characteristics of these interventions, determines the strategies used to adapt them to Arab culture successfully, assesses the feasibility and acceptability of the interventions, and evaluates the effectiveness of these interventions for service users and their families.

Method

Five electronic databases were searched including MEDLINE, CINAHL, Cochrane Library, PsycINFO and EMBASE for articles written in Arabic and English from inception to August 2019. Data were extracted and synthesised narratively.

Results

Six studies were retrieved from the search: three randomised control studies, two non-randomised studies and one qualitative study. There is limited evidence about culturally-adapted family interventions in the Arab region. However, the cultural adaptation process was comprehensive, and the implementation was reported to be feasible and acceptable. The methodological quality of the included studies was generally poor, so there is a risk of underestimating the effect size of the interventions due to lack of rigour and the presence of bias.

Conclusion

The present review provides the foundation for future work regarding family interventions in the Arab world, and confirms the feasibility of implementing such interventions with some modifications. Furthermore, the data suggests that any family-oriented intervention for schizophrenia is likely to be better than standard care in improving the outcome for patients and their families.
Does family communication moderate the association between adverse childhood experiences and emotional and behavioural problems?
Authors: Lackova Rebicova Miriama , Dankulincova Veselska Zuzana , Husarova Daniela , Klein Daniel , Madarasova Geckova Andrea , van Dijk Jitse P. , Reijneveld Sijmen A.
Published: August 2020

Background

Adverse childhood experiences (ACEs) and poor family support and communication can increase emotional and behavioural problems (EBP). Therefore, we assessed the association of difficult communication with mother and with father separately with both emotional and behavioural problems (EBP), and whether adolescents’ communication with mother and with father moderates the association of adverse childhood experiences (ACE) with the EBP of adolescents.

Methods

We used data from the Health Behaviour in School-aged Children study conducted in 2018 in Slovakia, comprising 5202 adolescents aged from 11 to 15 (mean age 13.53; 49.3% boys). EBP were measured using the Strengths and Difficulties Questionnaire. We used generalized linear regression adjusted for age, gender and family affluence to explore the modification of the associations between ACE and EBP by communication (easy vs. difficult communication) with mother and father.

Results

Difficult communication or a complete lack of communication due to the absence of mother and father increased the probability of emotional (exp (b): 0.96, 95% CI: 0.92|1.00; and 0.95, 95% CI: 0.91|0.99, respectively) and also of behavioural problems (exp (b): 0.96, 95% CI: 0.92|1.00; and 0.94, 95% CI: 0.90|0.97, respectively). We found a statistically significant interaction of communication with father on the association of ACE with EBP, showing that the joint effects were less than multiplicative.

Conclusion

Difficult communication with mother and father is related to EBP among adolescents, and adolescents’ communication with father moderates the association of ACE with both emotional and behavioural problems among adolescents.
Acceptability of pre-exposure prophylaxis for HIV prevention: facilitators, barriers and impact on sexual risk behaviors among men who have sex with men in Benin
Authors: Ahouada Carin , Diabaté Souleymane , Mondor Myrto , Hessou Septime , Guédou Fernand A. , Béhanzin Luc , Batona Georges , Gning Ndeye Ndiagna , Zannou D. Marcel , Alary Michel
Published: August 2020

Background

In Benin, men who have sex with men (MSM) do not always use condoms during anal sex. Pre-exposure prophylaxis (PrEP) using Truvada® (tenofovir disoproxil fumarate / emtricitabine) may be a complementary HIV prevention measure for MSM. This study aimed at identifying the potential facilitators and barriers to the use of PrEP.

Methods

This was a cross-sectional study conducted in 2018 among male-born MSM aged 18 years or older who reported being HIV-negative or unaware of their HIV status. The participants were recruited by the RDS technique (respondent driven sampling) in six cities of Benin. Logistic regression analyses, adapted to RDS statistical requirements, were performed to identify the factors associated with PrEP acceptability.

Results

Mean age of the 400 MSM recruited was 26.2 ± 5.0 years. PrEP was known by 50.7% of respondents. The intention to use PrEP was expressed by 90% of MSM. If PrEP effectiveness were 90% or more, 87.8% of the respondents thought they would decrease condom use. In multivariate analysis, the facilitators associated with PrEP acceptability were: not having to pay for PrEP (odds ratio (OR) = 2.39, 95% CI: 1.50–4.46) and its accessibility within MSM networks (OR = 9.82, 95% CI: 3.50–27.52). Only one barrier was significant: the concern that taking PrEP be perceived as marker of adopting HIV risky behaviors (OR = 0.11, 95% CI: 0.04–0.30).

Conclusion

In Benin, not all MSM know about PrEP. But once well informed, the majority seems willing to use it if made available. The free availability of the drug and its accessibility in the MSM networks are important facilitators. The possibility of decrease in condom use should not be a barrier to the prescription of PrEP if made available.
Preadolescents’ healthy eating behavior: peeping through the social norms approach
Authors: Ragelienė Tija , Grønhøj Alice
Published: August 2020

Background

The rising childhood obesity rate is a major public health challenge. The objective of this study is to examine key underlying mechanisms for peer-related social influence on preadolescents’ healthy eating behavior by including factors closely linked with the quality of preadolescents’ relationship with peers.

Methods

A cross-sectional study was conducted in a convenience sample of 278 Lithuanian preadolescents, recruited from a public school. A questionnaire containing sociodemographic questions, questions about food intake, peer-related social norms of healthy eating, social self-efficacy, vegetable preference, need for peer approval and feeling of belonging were applied. Data was analyzed using structural equation modeling.

Results

The results of the SEM showed that social self-efficacy predicts feeling of belonging to the peer group and need for peer approval. Feeling of belonging and need for peer approval predict actual intake of vegetables via injunctive norms of healthy eating. However, neither feeling of belonging nor need for peer approval predicted descriptive norms of healthy eating. Contrary to our expectations, descriptive norms were found to be unrelated with actual intake of vegetables, though vegetable preference predicted actual intake of vegetables. Vegetable preference was not predicted by injunctive or descriptive peers’ social norms of healthy eating.

Conclusions

The findings of this study offer insight for informing parents, teachers and for social norms marketing interventions by stressing the importance of social relations when the aim is to encourage healthy eating among preadolescents.
Do knee abduction kinematics and kinetics predict future anterior cruciate ligament injury risk? A systematic review and meta-analysis of prospective studies
Authors: Cronström Anna , Creaby Mark W. , Ageberg Eva
Published: August 2020

Background

To systematically review the association between knee abduction kinematics and kinetics during weight-bearing activities at baseline and the risk of future anterior cruciate ligament (ACL) injury.

Methods

Systematic review and meta-analysis according to PRISMA guidelines. A search in the databases MEDLINE (PubMed), CINAHL, EMBASE and Scopus was performed. Inclusion criteria were prospective studies including people of any age, assessing baseline knee abduction kinematics and/or kinetics during any weight-bearing activity for the lower extremity in individuals sustaining a future ACL injury and in those who did not.

Results

Nine articles were included in this review. Neither 3D knee abduction angle at initial contact (Mean diff: -1.68, 95%CI: − 4.49 to 1.14, ACL injury n = 66, controls n = 1369), peak 3D knee abduction angle (Mean diff: -2.17, 95%CI: − 7.22 to 2.89, ACL injury n = 25, controls n = 563), 2D peak knee abduction angle (Mean diff: -3.25, 95%CI: − 9.86 to 3.36, ACL injury n = 8, controls n = 302), 2D medial knee displacement (cm; Mean diff:: -0.19, 95%CI: − 0,96 to 0.38, ACL injury n = 72, controls n = 967) or peak knee abduction moment (Mean diff:-10.61, 95%CI: - 26.73 to 5.50, ACL injury n = 54, controls n = 1330) predicted future ACL injury.

Conclusion

Contrary to clinical opinion, our findings indicate that knee abduction kinematics and kinetics during weight-bearing activities may not be risk factors for future ACL injury. Knee abduction of greater magnitude than that observed in the included studies as well as factors other than knee abduction angle or moment, as possible screening measures for knee injury risk should be evaluated in future studies.
Five testicles in the genital area of a thirteen-month-old baby: a case report
Authors: Zahirian Moghadam Telma , Mohseni Rad Hamed , Zandian Hamed , Hosseinkhani Ali
Published: August 2020

Background

Polyorchidism is a congenital anomaly of the urogenital system and means more than two testes. It is a rare phenomenon, where there are no more than 200 reported cases in the literature. In this case, we report a 13-month year’s old case with five testicles.

Case presentation

We report a rare five testicles in the genital area of a 13-month-old baby. The initial diagnosis was undescended testis (UDT) based on ultrasound findings where a testis in the abdomen and a testis in the inguinal canal were detected. Surgery with general anaesthesia was performed to diagnose and treat this case. Before surgery, four HCG 1200u injections were administered. During the operation, it was determined that the case had had five testicles. Testicles were on the left in the proximal inguinal canal, and the sac hernia was ligated parallel to the inner ring. The patient was followed up several times after surgery by a urologist, and the results showed that there were no problems, and the intervention was uncomplicated.

Conclusion

Based on the result, it is not possible to diagnose such cases only by examination or ultrasound in infant patients, as the patient often presents with undescended testis (UDT), so the disease is diagnosed only through surgery.
Isolation of novel citrus and plum fruit promoters and their functional characterization for fruit biotechnology
Authors: Dasgupta Kasturi , Hotton Sara , Belknap William , Syed Yasra , Dardick Christopher , Thilmony Roger , Thomson James G.
Published: August 2020

Background

Promoters that confer expression in fruit tissues are important tools for genetic engineering of fruit quality traits, yet few fruit-specific promoters have been identified, particularly for citrus fruit development.

Results

In this study, we report five citrus fruit-specific/preferential promoters for genetic engineering. Additionally, we have characterized a novel fruit-preferential promoter from plum. Genes specifically expressed in fruit tissues were selected and their isolated promoter regions were fused with the GUSPlus reporter gene for evaluation in transgenic plants. Stable transformation in Micro-Tom tomato demonstrated that the candidate promoter regions exhibit differing levels of expression and with varying degrees of fruit specificity.

Conclusions

Among the five candidate citrus promoters characterized in this study, the CitSEP promoter showed a fruit-specific expression pattern, while the CitWAX and CitJuSac promoters exhibited high fruit-preferential expression with strong activity in the fruit, weak activity in floral tissues and low or undetectable activity in other tissues. The CitVO1, CitUNK and PamMybA promoters, while exhibiting strong fruit-preferential expression, also showed consistent weak but detectable activity in leaves and other vegetative tissues. Use of these fruit specific/preferential promoters for genetic engineering can help with precise expression of beneficial genes and help with accurate prediction of the activity of new genes in host fruit plants.
Development of Caco-2 cells expressing four CYPs via a mammalian artificial chromosome
Authors: Ohta Yumi , Kazuki Kanako , Abe Satoshi , Oshimura Mitsuo , Kobayashi Kaoru , Kazuki Yasuhiro
Published: August 2020

Background

Oral administration is the most common way to deliver drugs to the systemic circulation or target organs. Orally administered drugs are absorbed in the intestine and metabolized in the intestine and liver. In the early stages of drug development, it is important to predict first-pass metabolism accurately to select candidate drugs with high bioavailability. The Caco-2 cell line derived from colorectal cancer is widely used as an intestinal model to assess drug membrane permeability. However, because the expression of major drug-metabolizing enzymes, such as cytochrome P450 (CYP), is extremely low in Caco-2 cells, it is difficult to predict intestinal metabolism, which is a significant factor in predicting oral drug bioavailability. Previously, we constructed a mouse artificial chromosome vector carrying the CYP (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and P450 oxidoreductase (POR) (4CYPs-MAC) genes and increased CYP expression and metabolic activity in HepG2 cells via transfer of this vector.

Results

In the current study, to improve the Caco-2 cell assay model by taking metabolism into account, we attempted to increase CYP expression by transferring the 4CYPs-MAC into Caco-2 cells. The Caco-2 cells carrying the 4CYPs-MAC showed higher CYP mRNA expression and activity. In addition, high metabolic activity, availability for permeation test, and the potential to assess drug–drug interactions were confirmed.

Conclusions

The established Caco-2 cells with the 4CYPs-MAC are expected to enable more accurate prediction of the absorption and metabolism in the human intestine than parental Caco-2 cells. The mammalian artificial chromosome vector system would provide useful models for drug development.
Parental acceptance of silver Diamine fluoride application on primary dentition: a systematic review and meta-analysis
Authors: Sabbagh Heba , Othman Mashael , Khogeer Layla , Al-harbi Haifa , Al harthi Amjad , Abdulgader Yaseen Abdulgader Asmaa
Published: August 2020

Background

This systematic review of the literature was carried out to assess parental acceptance for silver diamine fluoride (SDF) application and esthetic outcome on their children primary dentition and evaluate factors that might influence their acceptance.

Methods

Our research protocol included a search strategy, inclusion/exclusion criteria, and a data extraction plan. The search engines we used were PubMed, Google Scholar, and Science Direct. Reviewers independently reviewed, determined and carried out quality assessment for included studies using CONSORT (for clinical-trials), and STROBE (for Observational studies). In addition, evidence and recommendation’s strength was conducted using Shekelle et al. system. Subsequently, a meta-analysis was performed to assess the association between parental acceptance for SDF treatment and teeth type, location and child’s cooperation.

Results

Eight studies fulfilled the inclusion criteria. There were statistically significant differences between parental acceptance for SDF usage on posterior teeth compared to anterior teeth (P < 0.001, OR: 0.23 and 95% CI: 0.15–0.34) and for SDF usage on anterior teeth of uncooperative compared to cooperative children (P < 0.001, OR: 0.27 and 95% CI: 0.17–0.44). Additionally, parent’s acceptance rate for SDF application increased after follow-up visits and education.

Conclusion

Parental acceptance for SDF treatment was significantly related to tooth location, child cooperation and pre-operative instruction.
Exploiting mutual information for the imputation of static and dynamic mixed-type clinical data with an adaptive k-nearest neighbours approach
Authors: Tavazzi Erica , Daberdaku Sebastian , Vasta Rosario , Calvo Andrea , Chiò Adriano , Di Camillo Barbara
Published: August 2020

Background

Clinical registers constitute an invaluable resource in the medical data-driven decision making context. Accurate machine learning and data mining approaches on these data can lead to faster diagnosis, definition of tailored interventions, and improved outcome prediction. A typical issue when implementing such approaches is the almost unavoidable presence of missing values in the collected data. In this work, we propose an imputation algorithm based on a mutual information-weighted k-nearest neighbours approach, able to handle the simultaneous presence of missing information in different types of variables. We developed and validated the method on a clinical register, constituted by the information collected over subsequent screening visits of a cohort of patients affected by amyotrophic lateral sclerosis.

Methods

For each subject with missing data to be imputed, we create a feature vector constituted by the information collected over his/her first three months of visits. This vector is used as sample in a k-nearest neighbours procedure, in order to select, among the other patients, the ones with the most similar temporal evolution of the disease over time. An ad hoc similarity metric was implemented for the sample comparison, capable of handling the different nature of the data, the presence of multiple missing values and include the cross-information among features captured by the mutual information statistic.

Results

We validated the proposed imputation method on an independent test set, comparing its performance with those of three state-of-the-art competitors, resulting in better performance. We further assessed the validity of our algorithm by comparing the performance of a survival classifier built on the data imputed with our method versus the one built on the data imputed with the best-performing competitor.

Conclusions

Imputation of missing data is a crucial –and often mandatory– step when working with real-world datasets. The algorithm proposed in this work could effectively impute an amyotrophic lateral sclerosis clinical dataset, by handling the temporal and the mixed-type nature of the data and by exploiting the cross-information among features. We also showed how the imputation quality can affect a machine learning task.
A system for automatically extracting clinical events with temporal information
Authors: Li Zhijing , Li Chen , Long Yu , Wang Xuan
Published: August 2020

Background

The popularization of health and medical informatics yields huge amounts of data. Extracting clinical events on a temporal course is the foundation of enabling advanced applications and research. It is a structure of presenting information in chronological order. Manual extraction would be extremely challenging due to the quantity and complexity of the records.

Methods

We present an recurrent neural network- based architecture, which is able to automatically extract clinical event expressions along with each event’s temporal information. The system is built upon the attention-based and recursive neural networks and introduce a piecewise representation (we divide the input sentences into three pieces to better utilize the information in the sentences), incorporates semantic information by utilizing word representations obtained from BioASQ and Wikipedia.

Results

The system is evaluated on the THYME corpus, a set of manually annotated clinical records from Mayo Clinic. In order to further verify the effectiveness of the system, the system is also evaluated on the TimeBank _Dense corpus. The experiments demonstrate that the system outperforms the current state-of-the-art models. The system also supports domain adaptation, i.e., the system may be used in brain cancer data while its model is trained in colon cancer data.

Conclusion

Our system extracts temporal expressions, event expressions and link them according to actually occurring sequence, which may structure the key information from complicated unstructured clinical records. Furthermore, we demonstrate that combining the piecewise representation method with attention mechanism can capture more complete features. The system is flexible and can be extended to handle other document types.
Mobile X-ray outside the hospital: a scoping review
Authors: Toppenberg Maria Dietz , Christiansen Thomas Erik Møller , Rasmussen Finn , Nielsen Camilla Palmhøj , Damsgaard Else Marie
Published: August 2020

Background

For several years mobile X-ray equipment has been routinely used for imaging in patients too unwell within the hospital, when transportation to the radiology department was inadvisable. Now, mobile X-ray examinations are also used outside the hospital. The literature describes that fragile patients may benefit from mobile X-ray, but we need to provide insights into the breadth, depth and gaps in a body of literature.

Methods

The scoping review was performed by searching PubMed, Cinahl, Embase, EconLit and Health Technology Assessment.

English-, Danish-, Norwegian-, German-, Italian-, French- and Swedish-language studies, published 1.1.2009–1.5.2020 about mobile X-ray outside the hospital were included.

Participants were patients examined using mobile X-ray as the intervention.

PRISMA was used when eligible to build up the review. To extract data from the selected articles, we used a structured summary table.

Results

We included 12 studies in this scoping review. The results were divided into four topics:1. Target population 2. Population health 3. Experience of care and 4. Cost effectiveness.

The main findings are that target population could be larger for instance including hospice patients for palliative care, group dwelling for people with intellectual disabilities, or psychiatric patients, population health may be improved, image quality seems to be good and mobile X-ray may be cost effective.

Limitations of language, databases and grey literature may have resulted in studies being missed.

Conclusions

Mobile X-ray may be used outside hospital. There seems to be potential benefits to both patients and health care staff. Based on the published studies it is not possible to draw a final conclusion if mobile X-ray examination is a relevant diagnostic offer and for whom. Further studies are needed to assess the feasibility of use in fragile patients, also regarding staff, relatives and societal consequences and therefore the topic mobile X-ray needs more research.
Examining healthcare professionals’ beliefs and actions regarding the physical health of people with schizophrenia
Authors: Berry Alexandra , Drake Richard J. , Yung Alison R.
Published: August 2020

Background

People with schizophrenia have a higher premature mortality risk compared with the general population mainly due to cardiovascular disease (CVD). Despite this, people with schizophrenia are less likely to access physical health services or have their physical health investigated and monitored.

Aims

To examine the beliefs and actions of mental health professionals regarding the physical health of people with schizophrenia.

Method

Two hundred and fifty-five healthcare professionals who support people with schizophrenia within Greater Manchester Mental Health NHS Foundation Trust (GMMH), United Kingdom and Pennine Care NHS Foundation Trust (PCFT), United Kingdom took part. Beliefs and actions were assessed using a self-administered questionnaire, which was constructed around two primary domains (1) CVD risk factors; and (2) physical health interventions. Descriptive statistics were reported and responses between different healthcare professional groups were compared.

Results

The overwhelming majority of participants were aware of established CVD risk factors with 98% identifying family history of CVD, 98% for smoking and 96% for high blood pressure. Most participants believed nearly all healthcare professionals were responsible for monitoring the physical health of people with schizophrenia, regardless of job speciality. There were 67% of participants who reported delivering an intervention to improve sedentary behaviour for people with schizophrenia. However, awareness of government and NHS recommended lifestyle interventions were low.

Conclusions

This study found good knowledge regarding many established CVD risk factors but little clarity regarding who is responsible for monitoring the physical health of people with schizophrenia and how often brief lifestyle interventions are being implemented.
Postbiotics-parabiotics: the new horizons in microbial biotherapy and functional foods
Authors: Nataraj Basavaprabhu H. , Ali Syed Azmal , Behare Pradip V. , Yadav Hariom
Published: August 2020

Probiotics have several health benefits by modulating gut microbiome; however, techno-functional limitations such as viability controls have hampered their full potential applications in the food and pharmaceutical sectors. Therefore, the focus is gradually shifting from viable probiotic bacteria towards non-viable paraprobiotics and/or probiotics derived biomolecules, so-called postbiotics. Paraprobiotics and postbiotics are the emerging concepts in the functional foods field because they impart an array of health-promoting properties. Although, these terms are not well defined, however, for time being these terms have been defined as here. The postbiotics are the complex mixture of metabolic products secreted by probiotics in cell-free supernatants such as enzymes, secreted proteins, short chain fatty acids, vitamins, secreted biosurfactants, amino acids, peptides, organic acids, etc. While, the paraprobiotics are the inactivated microbial cells of probiotics (intact or ruptured containing cell components such as peptidoglycans, teichoic acids, surface proteins, etc.) or crude cell extracts (i.e. with complex chemical composition)”. However, in many instances postbiotics have been used for whole category of postbiotics and parabiotics. These elicit several advantages over probiotics like; (i) availability in their pure form, (ii) ease in production and storage, (iii) availability of production process for industrial-scale-up, (iv) specific mechanism of action, (v) better accessibility of Microbes Associated Molecular Pattern (MAMP) during recognition and interaction with Pattern Recognition Receptors (PRR) and (vi) more likely to trigger only the targeted responses by specific ligand-receptor interactions. The current review comprehensively summarizes and discussed various methodologies implied to extract, purify, and identification of paraprobiotic and postbiotic compounds and their potential health benefits.
Consumption of ultra-processed foods and health outcomes: a systematic review of epidemiological studies
Authors: Chen Xiaojia , Zhang Zhang , Yang Huijie , Qiu Peishan , Wang Haizhou , Wang Fan , Zhao Qiu , Fang Jun , Nie Jiayan
Published: August 2020

Background

Consumption of ultra-processed foods (UPFs) plays a potential role in the development of obesity and other diet-related noncommunicable diseases (NCDs), but no studies have systematically focused on this. This study aimed to summarize the evidence for the association between UPFs consumption and health outcomes.

Methods

A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies. Epidemiological studies were included, and identified studies were evaluated for risk of bias.A narrative review of the synthesized findings was provided to assess the association between UPFs consumption and health outcomes.

Results

20 studies (12 cohort and 8 cross-sectional studies) were included in the analysis, with a total of 334,114 participants and 10 health outcomes. In a narrative review, high UPFs consumption was obviously associated with an increased risk of all-cause mortality, overall cardiovascular diseases, coronary heart diseases, cerebrovascular diseases, hypertension, metabolic syndrome, overweight and obesity, depression, irritable bowel syndrome, overall cancer, postmenopausal breast cancer, gestational obesity, adolescent asthma and wheezing, and frailty. It showed no significant association with cardiovascular disease mortality, prostate and colorectal cancers, gestational diabetes mellitus and gestational overweight.

Conclusions

This study indicated a positive association between UPFs consumption and risk of several health outcomes. Large-scale prospective designed studies are needed to confirm our findings.