bluuebunny/crossref_metadata_2025 huggingface dataset:
HELLO: improved neural network architectures and methodologies for small variant calling
Authors: Ramachandran Anand , Lumetta Steven S. , Klee Eric W. , Chen Deming
Published: August 2021

Background

Modern Next Generation- and Third Generation- Sequencing methods such as Illumina and PacBio Circular Consensus Sequencing platforms provide accurate sequencing data. Parallel developments in Deep Learning have enabled the application of Deep Neural Networks to variant calling, surpassing the accuracy of classical approaches in many settings. DeepVariant, arguably the most popular among such methods, transforms the problem of variant calling into one of image recognition where a Deep Neural Network analyzes sequencing data that is formatted as images, achieving high accuracy. In this paper, we explore an alternative approach to designing Deep Neural Networks for variant calling, where we use meticulously designed Deep Neural Network architectures and customized variant inference functions that account for the underlying nature of sequencing data instead of converting the problem to one of image recognition.

Results

Results from 27 whole-genome variant calling experiments spanning Illumina, PacBio and hybrid Illumina-PacBio settings suggest that our method allows vastly smaller Deep Neural Networks to outperform the Inception-v3 architecture used in DeepVariant for indel and substitution-type variant calls. For example, our method reduces the number of indel call errors by up to 18%, 55% and 65% for Illumina, PacBio and hybrid Illumina-PacBio variant calling respectively, compared to a similarly trained DeepVariant pipeline. In these cases, our models are between 7 and 14 times smaller.

Conclusions

We believe that the improved accuracy and problem-specific customization of our models will enable more accurate pipelines and further method development in the field. HELLO is available athttps://github.com/anands-repo/hello
Post cardiac injury syndrome successfully treated with medications: a report of two cases
Authors: Huang Mu-Shiang , Su Yan-Hua , Chen Ju-Yi
Published: August 2021

Background

Post cardiac injury syndrome (PCIS) is induced by myocardial infarction or cardiac surgery, as well as minor insults to the heart such as percutaneous coronary intervention (PCI), or insertion of a pacing lead. PCIS is characterized by pericarditis after injury to the heart. The relatively low incidence makes differential diagnosis of PCIS after PCI or implantation of a pacemaker a challenge. This report describes two typical cases of PCIS.

Case presentation

The first patient presented with signs of progressive cardiac tamponade that occurred two weeks after implantation of a permanent pacemaker. Echocardiography confirmed the presence of a moderate amount of newly-formed pericardial effusion. The second patient underwent PCI for the right coronary artery. However, despite an uneventful procedure, the patient experienced dyspnea, tightness of chest and cold sweats, and bradycardia two hours after the procedure. Echocardiography findings, which showed a moderate amount of newly-formed pericardial effusion, suggested acute cardiac tamponade, and compromised hemodynamics. Both patients recovered with medication.

Conclusion

These cases illustrated that PCIS can occur after minor myocardial injury, and that the possibility of PCIS should be considered if there is a history of possible cardiac insult.
Anatomical and positional variants of the brachiocephalic trunk in a Mexican population
Authors: Jasso-Ramírez Nadia Gabriela , Elizondo-Omaña Rodrigo E. , Garza-Rico Ingrid Abigail , Aguilar-Morales Kouatzin , Quiroga-Garza Alejandro , Elizondo-Riojas Guillermo , Treviño-González José Luis , Guzman-Lopez Santos
Published: August 2021

Background

Brachiocephalic trunk (BCT) variants may have a clinical impact during surgical procedures, some of which could be fatal. The objective of this study was to classify height positions of the BCT and report their prevalence in a Mexican population.

Methods

Patients: A retrospective, descriptive, observational, and cross-sectional was performed using computed tomography angiography (CTA) of adult (> 18 years of age) patients, without gender distinction, of Mexican origin. Measuring techniques were standardized using the suprasternal notch to analyze linear and maximum heights, linear and curved lengths, and the vertebral origin and bifurcation levels of the BCT.

Results

A total of 270 CTA were obtained (66.7% men and 33.3% women). A high position of BCT was present in 64.81% (n 175/270). The mean linear medial height was 0.58 ± 1.91 cm, the maximum height of the free edge was 3.85 ± 2.04 cm, side length of the midline at the maximum height of the free edge was 1.46 ± 2.59, linear length 3.72 ± 0.70, and a curve length 3.99 ± 0.79. The BCT origin was most predominant at the T3 (57.9%) and T4 (27.0%) vertebral levels, with the bifurcation at T2 (57.9%) and T1 (36.2%).

Conclusions

There is a high prevalence of high position BCT in our population. Patients should be assessed before any procedures in the area, due to the potential risk of complications.
Male partners’ participation in birth preparedness and complication readiness in low- and middle-income countries: a systematic review and meta-analysis
Authors: Boltena Minyahil Tadesse , Kebede Abraham Sahlemichael , El-Khatib Ziad , Asamoah Benedict Oppong , Boltena Andualem Tadesse , Tyae Hawult , Teferi Melese Yeshambaw , Shargie Mulatu Biru
Published: August 2021

Background

Maternal and neonatal health outcomes remain a challenge in low- and middle-income countries (LMICs) despite priority given to involving male partners in birth preparedness and complication readiness (BPCR). Men in LMICs often determine women’s access to and affordability of health services. This systematic review and meta-analysis determined the pooled magnitude of male partner’s participation in birth preparedness and complication readiness in LMICs.

Methods

Literature published in English language from 2004 to 2019 was retrieved from Google Scholar, PubMed, CINAHL, Scopus, and EMBASE databases. The Joanna Briggs Institute’s critical appraisal tool for prevalence and incidence studies were used. A pooled statistical meta-analysis was conducted using STATA Version 14.0. The heterogeneity and publication bias were assessed using the I2 statistics and Egger’s test. Duval and Tweedie's nonparametric trim and fill analysis using the random-effect analysis was carried out to validate publication bias and heterogeneity. The random effect model was used to estimate the summary prevalence and the corresponding 95% confidence interval (CI) of birth preparedness and complication readiness. The review protocol has been registered in PROSPERO number CRD42019140752. The PRISMA flow chart was used to show the number of articles identified, included, and excluded with justifications described.

Results

Thirty-seven studies with a total of 17, 148 participants were included. The pooled results showed that 42.4% of male partners participated in BPCR. Among the study participants, 54% reported having saved money for delivery, whereas 44% identified skilled birth attendants. 45.8% of male partners arranged transportation and 57.2% of study participants identified health facility as a place of birth. Only 16.1% of the male partners identified potential blood donors.

Conclusions

A low proportion of male partners were identified to have participated in BPCR in LMICs. This calls countries in low- and middle-income setting for action to review their health care policies, to remove the barriers and promote facilitators to male partner’s involvement in BPCR. Health systems in LMICs must design and innovate scalable strategies to improve male partner’s arrangements for a potential blood donor and transportation for complications that could arise during delivery or postpartum haemorrhage.
Construction of a prognostic signature of autophagy-related lncRNAs in non-small-cell lung cancer
Authors: Zhang Xinyang , Cao Yu , Chen Li
Published: August 2021

Background

Autophagy inhibits tumorigenesis by limiting inflammation. LncRNAs regulate gene expression at various levels as RNAs; thus, both autophagy and lncRNAs are closely related to the occurrence and development of tumours.

Methods

A total of 232 autophagy-related genes were used to construct a coexpression network to extract autophagy-related lncRNAs. A prognostic signature was constructed by multivariate regression analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was applied to analyse enrichment in cancer-related pathways. Immune infiltration analysis was used to analyse the relationship between the prognostic signature and the tumour microenvironment.

Results

Nine autophagy-related lncRNAs were used to construct a prognostic model for non-small-cell lung cancer. The median risk score was used to discriminate the high- and low-risk groups, and the low-risk group was found to have better survival. Because KEGG pathway analysis showed that the prognostic signature was enriched in some immune pathways, further analysis of immune infiltration was conducted, and it was found that the prognostic signature did play a unique role in the immune microenvironment. Additionally, the prognostic signature was associated with clinical factors.

Conclusion

We constructed a prognostic model of autophagy-related lncRNAs that can predict the prognosis of non-small-cell lung cancer.
Long-term outcomes of intravitreal anti-VEGF therapies in patients affected by neovascular age-related macular degeneration: a real-life study
Authors: Corazza Paolo , D’Alterio Francesco Maria , Kabbani Jamil , Alam Mostafa Mohamed Ragheb , Mercuri Stefano , Orlans Harry Otway , Younis Saad
Published: August 2021

Purpose

To describe real-life data from wet age-related macular degeneration (AMD) patients treated with anti-vascular endothelial growth factors (VEGFs) and to compare our results with previous studies and clinical trials.

Methods

This retrospective monocentric cohort study analyzed 865 eyes of 780 wet-AMD patients treated with an anti-VEGF treat-and-extend regimen over a long-term follow-up period. Aflibercept and Ranibizumab were considered first-line agents whereas Bevacizumab was reserved for use on a compassionate basis in patients not meeting treatment criteria. All patients underwent a best corrected visual acuity (BCVA) assessment at each follow-up visit.

Results

One-year follow-up figures were available for 82.5% of patients, whilst follow-up data was recorded for 55.6%, 37.6%, 25.1%, and 15.0% of the cohort at years 2, 3, 4, and 5 respectively. Patients treated with Bevacizumab received fewer yearly injections than those treated with Ranibizumab. However, no significant difference in the number of injections per year was detected in other comparisons between groups. Whilst our data showed no significant difference in mean BCVA between the three groups, there was a gradual deterioration of visual function over time for the patient cohort as a whole.

Conclusion

No significant differences between the 3 anti-VEGF molecules were recorded in wet-AMD patients in real-life conditions. Despite the long-term therapy, we found a slight reduction in visual function especially after the third year of treatment.
Influence of the interaction between parental myopia and poor eye habits when reading and writing and poor reading posture on prevalence of myopia in school students in Urumqi, China
Authors: Shi Haonan , Fu Jing , Liu Xiaojing , Wang Yingxia , Yong Xianting , Jiang Lan , Ma Shaowei , Yin Zhe , Yao Jian , Yao Xuan , Chen Xueyi , Wang Tingting
Published: August 2021

Background

To evaluate the prevalence of myopia in school students in Urumqi, China, and explore the influence of the interaction between parental myopia and poor reading and writing habits on myopia to identify the at-risk population and provide evidence to help school students avoid developing myopia.

Methods

A cross-sectional survey was conducted with 6,883 school students aged 7–20 years in Urumqi in December 2019. The Standard Eye Chart and mydriatic optometry were used to determine whether students had myopia. Falconer’s method was used to calculate the heritability of parental myopia. Multivariate unconditional logistic regression models were used to analyze the risk factors for myopia and the additive and multiplicative interaction of parental myopia and poor reading and writing habits.

Results

After standardizing the age of the 6,883 students, the overall prevalence rate of myopia was 47.50 %. The heritability of parental myopia was 66.57 % for boys, 67.82 % for girls, 65.02 % for the Han group, and 52.71 % for other ethnicities. There were additive interactions between parental myopia and poor reading and writing habits; among them, parental myopia and poor eye habits when reading and writing (the distance between the eyes and book is less than 30 cm when reading and writing, fingers block the sight of one eye while holding the pen, and leaning one’s body when reading and writing; habit 1) increased the risk of myopia by 10.99 times (odds ratio [OR] = 10.99, 95 % confidence interval [CI] = 8.33–14.68), parental myopia and poor reading posture (reading while lying down, walking, or in the car; habit 2) increased the risk of myopia by 5.92 times (OR = 5.92, 95 % CI = 4.84–7.27). There was no multiplicative interaction between parental myopia and habit 1 or habit 2 (OR = 0.69, 95 % CI = 0.44–1.08; OR = 0.89, 95 % CI = 0.66–1.21, respectively).

Conclusion

The prevalence of myopia among students in Urumqi, Xinjiang is relatively high. The risk of developing myopia is affected by parental myopia and poor reading and writing habits. In addition, parental myopia amplifies the harm caused by poor reading and writing habits, thereby increasing the risk of myopia. Students with parents who have myopia should be targeted during myopia prevention efforts.
Astigmatic correction of simultaneous femtosecond laser-assisted cataract surgery (FLACS) with intrastromal arcuate keratotomy (ISAK) versus Toric intraocular Lens Impantation with conventional phacoemulsification
Authors: Kwon Hye Ji , Lee Hun , Lee Jin Ah. , Kim Jae Yong , Tchah Hungwon
Published: August 2021

Background

To compare the efficacies in astigmatic correction of simultaneous femtosecond laser-assisted cataract surgery (FLACS) with intrastromal arcuate keratotomy (ISAK) versus toric intraocular lens (IOL) implantation with conventional phacoemulsification in moderate astigmatism.

Methods

A retrospective chart review was conducted for patients who had undergone cataract surgery by one surgeon. We identified patients with preoperative corneal astigmatism from + 0.75 to + 2.00 diopters (D) who had undergone astigmatic correction with FLACS with ISAK or toric IOL implantation with conventional phacoemulsification. We measured the visual acuity, intraocular pressure, automated keratometer, manifest refraction, and topography preoperatively and 1-day, 1-month, 3-month, and 6-month postoperatively. The vector analysis of refractive astigmatism was performed.

Results

Of a total of 48 eyes of 48 patients, 27 eyes of 27 patients had FLACS with ISAK (AK group), and 21 eyes of 21 patients had conventional cataract surgery with toric IOL implantation (toric IOL group). Refractive astigmatism was significantly decreased in both groups. The mean preoperative and 6-month postoperative refractive astigmatism were 1.85 ± 1.07 and 0.99 ± 0.51 D, respectively, in the AK group (P = 0.028), and 1.84 ± 0.81 and 0.68 ± 0.21 D, respectively, in the toric IOL group (P < 0.001). There was no significant difference in refractive astigmatism between the two groups at 6-month postoperatively (0.99 ± 0.51 vs 0.68 ± 0.21 D, P = 0.057). At 6-month postoperatively, parameters for vector analysis of refractive astigmatism showed no statistical difference between the two groups. Corneal astigmatism was significantly decreased in the AK group. Corneal astigmatism from topography and the automated keratometer were significantly lower in the AK group 6-month postoperatively compared to toric IOL group (0.94 ± 0.40 vs. 1.53 ± 0.46 D, P = 0.018 for topography; and 0.98 ± 0.69 vs. 1.37 ± 0.41 D, P = 0.032 for the automated keratometer).

Conclusions

FLACS with ISAK could be an effective procedure for reducing astigmatism as well as toric IOL implantation in cataract surgery.
Cannabidiol versus risperidone for treatment of recent-onset psychosis with comorbid cannabis use: study protocol for a randomized controlled clinical trial
Authors: Rasmussen Jesper Østrup , Jennum Poul , Linnet Kristian , Glenthøj Birte Y. , Baandrup Lone
Published: August 2021

Background

Cannabis use is an important risk factor for development of psychosis and further transition to schizophrenia. The prevalence of patients with psychosis and comorbid cannabis use (dual diagnosis) is rising with no approved specialized pharmacological treatment option. Cannabidiol, a constituent of theCannabis sativaplant, has potential both as an antipsychotic and as a cannabis substituting agent.

The aim of this study is to evaluate the efficacy of cannabidiol versus a first-choice second-generation antipsychotic (risperidone) in patients with early psychosis and comorbid cannabis use.

Methods

The study is a phase II randomized, double-blinded, parallel-group, active-comparator clinical trial. We plan to include 130 patients aged between 18 and 64 years with a recent diagnosis of psychosis, comorbid cannabis use, and currently not treated with antipsychotics. The participants will be randomized to seven weeks of treatment with either cannabidiol 600 mg (300 mg BID) or risperidone 4 mg (2 mg BID). Participants will undergo clinical assessment after 1, 3, 5 and 7 weeks, telephone assessment the weeks in between, and a safety visit two weeks after end of treatment. The primary outcomes are cessation of cannabis use (self-reported) and psychotic symptom severity. The secondary outcomes include frequency and quantity of cannabis use, global illness severity, psychosocial functioning, subjective well-being, cognition, sleep, circadian rhythmicity, and metabolomics.

Discussion

The results of this trial can potentially contribute with a new treatment paradigm for patients suffering from dual diagnosis.

Trial registration

ClinicalTrials.gov,NCT04105231, registered April 23rd, 2021
Secular trends and regional variations in pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD) among children and adolescents in Germany
Authors: Akmatov Manas K. , Holstiege Jakob , Bätzing Jörg
Published: August 2021

Background

The study aim was to examine the secular trends and regional variations in pharmacotherapy of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Germany.

Methods

We used nationwide drug prescription data of outpatient care (2009 to 2016). The study population comprised patients aged between 5 and 14 years with the diagnoses “hyperkinetic disorders” (ICD-10 code F90) (e.g. n = 262,766 in 2016). The examined drugs were methylphenidate, amphetamines, atomoxetine and guanfacine.

Results

Overall, the proportion of patients received any prescription showed a decreasing trend over years (2010, 51%; 2016, 44%). The proportion of methylphenidate prescription was higher in Western than Eastern federal states. However, atomoxetine was more often prescribed in Eastern than Western federal states. The proportion of methylphenidate prescriptions issued by pediatric psychiatrists increased from 28% (2009) to 41% (2016).

Conclusion

A decreasing trend in use of pharmacotherapy may be explained by prescription restrictions issued by the Federal Joint Committee in recent years.
Variations in perceptions of parenting role related to children’s physical activity and sedentary behaviours – a qualitative study in a Northern European context
Authors: Andermo Susanne , Rydberg Helena , Norman Åsa
Published: August 2021

Background

The aim of the study was to increase understanding of the variation in parental perceptions of their roles and responsibilities in relation to children’s physical activity and sedentary behaviours.

Methods

This qualitative study was based on data from the Healthy School Start intervention study II, in the form of recorded motivational interviewing (MI) sessions with mothers and fathers participating in the intervention. Forty-one MI sessions where parents discussed physical activity and/or sedentary behaviour were selected for analysis. Data analysis was performed using a phenomenographic approach.

Results

Three categories describing a structural relationship of parents’ different views on their own role in relation to their child’s habits were identified: 1) The parent decides – Child physical activity according to my beliefs and views as a parent and where I, as a parent, decide, 2) Parent-child interaction – child physical activity is formed in interaction between me as a parent and my child or 3) The child/someone else decides – The child or someone other than me as a parent decides or has the responsibility for my child’s physical activity. All three categories included four subcategories of specific activities: organised activity, activity in everyday life, being active together and screen time, describing practical approaches used in each of the three categories.

Conclusions

This study found variation in mothers’ and fathers’ perceptions of their roles and responsibilities for their child’s physical activity and sedentary behaviours related to specific types of activities. The results indicate areas where parents need support in how to guide their children and how parental responsibility can have a positive influence on children’s physical activity and sedentary habits.
Novel compound heterozygous mutations of DNAH5 identified in a pediatric patient with Kartagener syndrome: case report and literature review
Authors: Wang Lina , Zhao Xin , Liang Hang , Zhang Li , Li Chunyan , Li Deli , Meng Xiangfeng , Meng Fanzheng , Gao Mao
Published: August 2021

Background

Kartagener syndrome is a subtype of primary ciliary dyskinesia that may exhibit various symptoms including neonatal respiratory distress and frequent infections of the lung, sinus and middle ear because of the impaired function of motile cilia. In addition to typical symptoms of primary ciliary dyskinesia, patients with Kartagener syndrome also show situs inversus. It is an autosomal recessive disorder which is mostly caused by mutations inDNAH5. Kartagener syndrome is often underdiagnosed due to challenges in the diagnosis process. As next-generation sequencing becomes widely used in clinical laboratories, genetic testing provides an accurate approach to the diagnosis of Kartagener syndrome.

Case presentation

A 7-year-old female patient presented with runny nose of 6 years duration and recurrent cough with phlegm of 2 years duration. Kartagener syndrome was diagnosed through diagnostic tests such as nasal nitric oxide (NO) concentration and transmission electron microscopy, and after performing other exams that corroborated the diagnosis, such as computed tomography, bronchoscopy and hearing test. Whole-exome sequencing was performed for the patient and both parents. The pediatric patient was diagnosed as Kartagener syndrome with the typical symptoms of ciliary dyskinesia including bronchiectasis, sinusitis, conductive hearing loss and situs inversus along with a reduced nasal NO concentration and ciliary abnormalities. The patient carried two novel compound heterozygous mutations inDNAH5, NM_001369:c.12813G > A (p. Trp4271Term) and NM_001369:c.9365delT (p. Leu3122Term). Both mutations lead to premature stop codons and thus are pathogenic. The p. Trp4271Term and p. Leu3122Term mutations were inherited from the father and the mother of the patient individually. A literature review was also conducted to summarizeDNAH5mutations in pediatric patients with Kartagener syndrome across different ethnic groups.

Conclusions

Our study provides a good example of the diagnosis of Kartagener syndrome in pediatric patients using a series of diagnostic tests combined with genetic testing. Two novel loss-of-function mutations inDNAH5were identified and validated in a pediatric patient with Kartagener syndrome.
A novel vertebral trench technique (VTT) involving transforaminal endoscopic lumbar foraminotomy (TELF) for very highly up-migrated lumbar disc herniation above L5
Authors: Yu Yong , Jiang Ye , Xu Fuling , Mao Yuhang , Yuan Lutao , Li Chen
Published: August 2021

Background

Percutaneous endoscopic lumbar discectomy (PELD) has become popular for the treatment of symptomatic lumbar disc herniation (LDH). The very highly up-migrated lumbar disc herniation (VHUM-LDH) is difficult to remove under PELD. The purpose of this research is to investigate the feasibility, clinical efficacy and operative nuances of a novel VTT involving TELF for this type of herniation.

Methods

Eleven patients with very highly up-migrated LDH who underwent VTT involving TELF discectomy from May 2016 to May 2019 were included in this study. The operative time, length of hospital stay, and postoperative complications were recorded. Pre-and postoperative radiologic findings were investigated. All the patients were followed more than 1 year. The visual analogue score (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores and modified MacNab criteria were used to assess surgical efficacy.

Results

All the 11 patients underwent successful surgery. We compared the VAS, ODI, and JOA scores before and after surgery. The differences were statistically significant (P < 0.05). According to the modified MacNab criteria, 10 patients were assessed as “excellent”, 1 patient was assessed as “good” at the last follow up.

Conclusion

The novel VTT involving TELF discectomy is a supplement to the traditional PELD. This technique enables the endoscope with working cannula to get closer the sequestrated nucleus pulposus without irritating the exiting nerve root, and facilitates the nucleus pulposus be removed successfully under direct visualization. The VTT involving TELF discectomy can be a safe, effective and feasible surgical procedure for the treatment of LDH with very highly up-migrated.
A criteria-based rehabilitation program for chronic mid-portion Achilles tendinopathy: study protocol for a randomised controlled trial
Authors: Griffin Colin , Daniels Katherine , Hill Caroline , Franklyn-Miller Andrew , Morin Jean-Benoît
Published: August 2021

Background

Achilles tendinopathy (AT) is a common overuse injury in running-related sports where patients experience pain and impaired function which can persist. A graded rehabilitation program has been successful in reducing pain and improving function to enable a return to sport. The aim of this study is to compare the effectiveness of a criteria-based rehabilitation program including strength and reactive strength targets, with a previously successful rehabilitation program on changes in pain and function using the Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire. Secondary aims will be to assess changes in calf strength, reactive strength, and lower limb running and forward hop biomechanics over the course of a 12-week rehabilitation program, and long-term follow-up investigations.

Methods

Sixty eligible participants with chronic mid-portion AT who train in running-based sports will be included in this study. They will be randomly assigned to a group that will follow an evidence-based rehabilitation program of daily exercises with progression guided by symptoms or a group performing 3 high-intensity rehabilitation sessions per week with individualised load targets progressing to reactive strength exercises. Testing will take place at baseline, week 6 and 12. Plantar flexor peak torque will be measured using isokinetic dynamometry, reactive strength will be measured using a drop jump and lower limb biomechanical variables will be measured during a single leg forward hurdle hop test and treadmill running using 3D motion analysis. Follow-up interviews will take place at 6, 12 and 24 months after beginning the program which will assess patient participation in sport and possible re-injury.

Discussion

This is the first study to propose an individualised criteria-based graded rehabilitation program in patients in with chronic mid-portion Achilles tendinopathy where progression is guided by strength and reactive strength outcome measures. This study will provide a comprehensive assessment of plantar flexor strength, reactive strength and lower limb biomechanical variables in running and forward hopping with the VISA-A questionnaire as the primary outcome measure and long term post-intervention follow-up assessments performed.

Trial registration

ClinicalTrials.gov(ID:NCT04384874). Registered retrospectively on April 23rd 2020.
Osteoporosis is associated with varus deformity in postmenopausal women with knee osteoarthritis: a cross-sectional study
Authors: Zhang Cheng , Zhuang Zhikun , Chen Xiaojun , Li Keda , Lin Tianye , Pang Fengxiang , Zhang Ying , He Wei , Wei Qiushi
Published: August 2021

Background

Varus deformity of the knee is a common pathological characteristic in knee osteoarthritis (KOA), and not enough attention has been given to the relationship between knee varus deformity and the state of systemic bone mass. The purpose of this study was to evaluate the potential relationship between bone mineral density (BMD) and varus deformity in postmenopausal women with KOA.

Methods

A total of 202 postmenopausal women with KOA(KL grade ≥ 2)in our department from January 2018 to June 2020 were reviewed in this cross-sectional study. The hip-knee-ankle angle of the lower extremity (HKA), medial distal femoral angle (MDFA), medial proximal tibial angle (MPTA), and the angle of the joint line (JLCA) were measured in all patients. According to the HKA Angle, these participants were divided into the varus deformity group (HKA < 175.3°) and the normal limb alignment group (175.3°≤ HKA ≤ 180.3°). The BMD of the lumbar (L1-L4), left femoral neck, and left hip were measured by dual-energy X-ray absorptiometry in all patients. The difference in BMD between the knee varus deformity group and the normal limb alignment group was compared, and the relationship between the different angles of limb alignment and the BMD values at different sites was evaluated.

Results

There were 144 cases (71.3 %) in the varus deformity group and 58 cases (28.7 %) in the normal limb alignment group. BMD at different joint sites within the knee varus deformity group was lower than of the normal limb alignment group, and the prevalence of osteoporosis was higher. After adjusting for confounding factors such as age, BMI, pain duration, and affected side, binary logistic regression showed that osteoporosis was an independent risk factor for varus deformity of KOA, and multiple linear regression showed that the BMD of spine, femoral neck, and hip was significantly associated with varus deformity of KOA. Pearson correlation analysis showed that BMD of the lumbar spine (L1-L4), left femoral neck and left hip joint were positively correlated with the HKA, but negatively correlated with JLCA. MPTA was positively correlated with the left femoral neck and left hip joint BMD, but not correlated with lumbar bone density. Furthermore, in the normal limb alignment group, the HKA was only negatively correlated with JLCA, but not significantly correlated with MDFA and MPTA. In the varus deformity group, the HKA was not only negatively correlated with JLCA but also positively correlated with MDFA and MPTA.

Conclusions

Osteoporosis should be a major risk factor for varus deformity in postmenopausal women with KOA. The progression of varus deformity of the knee should be concerned in postmenopausal women who simultaneously has KOA and osteoporosis.
Relationship between fatty liver change and nutritional status after total gastrectomy in gastric cancer patients: a retrospective study
Authors: Nakamura Naohiko , Kinami Shinichi , Fujita Jun , Kaida Daisuke , Tomita Yasuto , Miyata Takashi , Miyashita Tomoharu , Fujita Hideto , Ueda Nobuhiko , Takamura Hiroyuki
Published: August 2021

Background

The relationship between chronological nutritional changes and development of fatty liver after total gastrectomy (TG) in gastric cancer (GC) patients is still unclear. This study aimed to evaluate relationship between development of fatty liver and chronological changes of nutritional parameters during 12 months after TG.

Methods

We retrospectively analyzed medical records of 59 patients with GC who underwent TG at the Kanazawa Medical University Hospital between January 2009 and December 2017. We defined fatty liver change as a mean liver-to-spleen attenuation ratio (L/S ratio) of less than 1.2 in the computed tomography images at 12 months after TG and divided the patients into fatty liver (FL) and non-FL groups from the L/S ratio. We analyzed serum levels of total protein and albumin, and psoas muscle index (PMI) before TG and at 6 and 12 months after TG in the non-FL and FL groups.

Results

Six patients showed an L/S ratio of less than 1.2 at 12 months after TG and were included into FL group. There was no significant difference between the groups in serum parameters, L/S ratio, and PMI before TG. In the FL group, the mean levels of total protein and albumin decreased after TG and were significant lower at 6 months, compared with the non-FL group. And then, these levels in the FL group recovered at 12 months. In contrast, the mean levels of total protein and albumin in the non-FL group did not decrease below the preoperative levels throughout the year after surgery. As with laboratory parameters, all patients in the FL group showed decrease of PMI at 6 months after TG. This proportion was significantly higher than that in the non-FL group (100% vs. 40.8%, P = 0.006).

Conclusions

We evaluated that the patients with fatty liver occurring after TG had significantly lower levels of serum nutritional parameters and skeletal muscle index at 6 months, not but 12 months, after TG.
Expression pattern and regulatory effect of lysine-specific demethylase 2A gene in clear cell renal cell carcinoma
Authors: Wang Jiannan , Li Tan , Li Xiang , Zhang Yixia , Wang Xuemei
Published: August 2021

Background

Our study aimed to explore the expression and the biological role of lysine-specific demethylase 2A (KDM2A) in clear cell renal cell carcinoma (ccRCC).

Methods

In vitro, KDM2A expression was measured by qRT-PCR and western blot. A total of 50 patients with ccRCC were included, and KDM2A expression in ccRCC tissues was assessed by qRT-PCR and immunohistochemistry. The effects of KDM2A expression on cell biological behavior were examined by cell counting kit-8 assay, transwell assay and flow cytometry, respectively. The prognostic value of KDM2A in ccRCC was evaluated by Kaplan–Meier method.

Results

The KDM2A expression was significantly upregulated in ccRCC cell line (P < 0.05). Compared with para cancer tissues, ccRCC samples showed a higher KMD2A mRNA level and a larger proportion of high KDM2A expression (allP < 0.05). High KDM2A mRNA expression was more likely to occur in ccRCC tissues with tumor size > 7 cm (P = 0.005) and T3-T4 stage (P = 0.047). Knockdown of KDM2A significantly suppressed the proliferation and invasion, and promoted the apoptosis of ccRCC cells (allP < 0.05). Moreover, Kaplan–Meier survival analysis revealed that higher level of KDM2A expression in ccRCC patients was associated with lower survival rate (P = 0.004).

Conclusions

Our findings demonstrated a vital role of KDM2A in the pathogenesis of ccRCC, which provides a new perspective to understand the underlying molecular mechanisms in ccRCC.
Areca catechu-(Betel-nut)-induced whole transcriptome changes in a human monocyte cell line that may have relevance to diabetes and obesity; a pilot study
Authors: Cardosa Shirleny R , Ogunkolade B. William , Lowe Rob , Savage Emanuel , Mein Charles A , Boucher Barbara J , Hitman Graham A
Published: August 2021

Background

Betel-nut consumption is the fourth most common addictive habit globally and there is good evidence linking the habit to obesity, type 2 diabetes (T2D) and the metabolic syndrome. The aim of our pilot study was to identify gene expression relevant to obesity, T2D and the metabolic syndrome using a genome-wide transcriptomic approach in a human monocyte cell line incubated with arecoline and its nitrosated products.

Results

The THP1 monocyte cell line was incubated separately with arecoline and 3-methylnitrosaminopropionaldehyde (MNPA) in triplicate for 24 h and pooled cDNA indexed paired-end libraries were sequenced (Illumina NextSeq 500). After incubation with arecoline and MNPA, 15 and 39 genes respectively had significant changes in their expression (q < 0.05, log fold change 1.5). Eighteen of those genes have reported associations with T2D and obesity in humans; of these genes there was most marked evidence for CLEC10A, MAPK8IP1, NEGR1, NQ01 and INHBE genes.

Conclusions

Our preliminary studies have identified a large number of genes relevant to obesity, T2D and metabolic syndrome whose expression was changed significantly in human TPH1 cells following incubation with betel-nut derived arecoline or with MNPA. These findings require validation by further cell-based work and investigation amongst betel-chewing communities.
Influence of cognitive impairment and dementia on oral health and the utilization of dental services
Authors: Jockusch Julia , Hopfenmüller Werner , Nitschke Ina
Published: August 2021

Background

The aim of this study was to show the influence of cognitive impairment and dementia on oral health and on the utilization of dental services.

Methods

A cross-sectional analyzation of data of the OrBiD (Oral Health, Bite Force and Dementia) pilot study was conducted. 137 subjects were stratified into five dementia groups on the basis of the Mini Mental State Examination (MMSE) (1—no dementia (MMSE 28–30), 2—mild cognitive impairment (MMSE 25–27), 3—mild dementia (MMSE 18–24), 4—moderate dementia (MMSE 10–17), and 5—severe dementia (MMSE < 10)). Information on the utilization of dental services and oral health parameters (DMFT index, degree of restoration, Periodontal Screening Index, Bleeding on Probing, Oral Hygiene Index, Denture Hygiene Index) were collected.

Results

An increase in dementia resulted in significant reduction in utilization. Moreover, with increasing cognitive impairment/dementia there was a significant difference in the number of teeth that were decayed, but not in the number of filled or missing teeth or the DMF/T index itself. With increasing dementia, the degree of restoration decreased and oral/denture hygiene deteriorated significantly. Nevertheless, periodontal therapy was required for all subjects independent of their degree of dementia while bleeding on probing was increasing with increasing dementia.

Conclusions

An influence of cognitive impairment and dementia on oral health and on the utilization of dental services was shown. However, no conclusions about the influence of the utilization behavior of people with dementia on oral health parameters can be drawn. Further longitudinal studies are needed.

Trial registrationClinicalTrials.gov NCT03775772. Registered 14th December 2018,https://clinicaltrials.gov/ct2/show/NCT03775772.
Adaptation of the Australian Palliative Care Phase concept to the German palliative care context: a mixed-methods approach using cognitive interviews and cross-sectional data
Authors: Lehmann Eva , Hodiamont Farina , Landmesser Mirjam , Knobloch Carina S. , Nauck Friedemann , Ostgathe Christoph , Grüne Bettina , Bausewein Claudia
Published: August 2021

Background

Palliative care phases (stable, unstable, deteriorating, terminal and bereavement) are routinely used in Australia and the UK to describe the clinical situation of patients and their families and to evaluate the associated care plan. In addition, it serves as a benchmark developed by the Australian Palliative Care Outcome Collaboration (PCOC) and is used nationwide for comparisons between services. In Germany, the concept is not used consistently due to various translations. Furthermore, there is no nationwide systematic approach to routinely assess clinical outcomes in palliative care.

The study aims to develop a German version of the palliative care phase definitions by adapting them culturally, and to examine the inter-rater reliability of the adjusted definitions with healthcare professionals.

Methods

Mixed-methods approach: Cognitive interview study using ‘think aloud’ and verbal probing techniques and a consecutive multi-center cross-sectional study with two clinicians independently assigning the phase definitions. Interviewees/participants were selected through convenience and purposive sampling in specialist palliative care inpatient units, advisory and community services and in three specialist palliative care units with doctors, nursing staff and allied health professionals.

Results

Fifteen interviews were conducted. Identified difficulties were: Some translated terms were 1) not self-explanatory (e.g. ‘family/carer’ or ‘care plan’) and (2) too limited to the medical dimension neglecting the holistic approach of palliative care. (3) Problems of comprehension regarding the concept in general occurred, e.g. in differentiating between the ‘unstable’ and ‘deteriorating’ phase. Inter-rater reliability was moderate (kappa = 0.44; 95% CI = 0.39–0.52). The assignment of the phase ‘deteriorating’ has caused the most difficulties.

Conclusion

Overall, the adapted palliative care phases are suitable to use in the German specialist palliative care setting. However, the concept of the phases is not self-explanatory. To implement it nationwide for outcome measurement/benchmarking, it requires further education, on-the-job training and experience as well as the involvement of healthcare professionals in implementation process. For the use of international concepts in different healthcare systems, a deeper discussion and cultural adaptation is necessary besides the formal translation.
South African traditional values and beliefs regarding informed consent and limitations of the principle of respect for autonomy in African communities: a cross-cultural qualitative study
Authors: Akpa-Inyang Francis , Chima Sylvester C.
Published: August 2021

Background

The Western-European concept of libertarian rights-based autonomy, which advocates respect for individual rights, may conflict with African cultural values and norms. African communitarian ethics focuses on the interests of the collective whole or community, rather than rugged individualism. Hence collective decision-making processes take precedence over individual autonomy or consent. This apparent conflict may impact informed consent practice during biomedical research in African communities and may hinder ethical principlism in African bioethics. This study explored African biomedical researchers' perspectives regarding informed consent and potential limitations to the principle of respect for autonomy in African communities.

Methods

We conducted a qualitative study based on in-depth interviews with 12 biomedical researchers, five females and seven males aged 34 to 74 years, currently working at an African university. Interviews lasted 35–40 min each and involved semi-structured open-ended interviews, which allowed participants to offer information about their perceptions and feelings regarding respect for autonomy and informed consent as practised in Africa. Empirical data from the interviews were recorded, transcribed, and analysed using thematic content analysis, together with an interrogation of relevant scientific literature about African communitarian ethics, making evaluations and drawing inferences consistent with the empirical bioethics approach.

Results

Based on these interviews and analysis of relevant literature, we found that informed consent is difficult to apply in an African context because it derives from a Western conception of libertarian rights-based autonomy. Most respondents pointed out that it was challenging to implement informed consent in the African setting. Furthermore, communalism, customary beliefs, spirituality, and relational autonomy are predominant in most African communities, as exemplified by the African moral philosophies ofUbuntu/BothoandUkama, which emphasize communitarianism over individual rights. We also found that language, education, poverty, and cultural beliefs are barriers to obtaining proper informed consent in African communities.

Conclusions

We conclude that there are limitations to applying the principle of respect for autonomy and informed consent in African communities, especially in the context of human biomedical research. We recommend using a more relational approach, such as Ross’s prima facie duties, to implement informed consent in African communities.
Patients-centered SurvivorShIp care plan after Cancer treatments based on Big Data and Artificial Intelligence technologies (PERSIST): a multicenter study protocol to evaluate efficacy of digital tools supporting cancer survivors
Authors: Mlakar Izidor , Lin Simon , Aleksandraviča Ilona , Arcimoviča Krista , Eglītis Jānis , Leja Mārcis , Salgado Barreira Ángel , Gómez Jesús G. , Salgado Mercedes , Mata Jesús G. , Batorek Doroteja , Horvat Matej , Molan Maja , Ravnik Maja , Kaux Jean-François , Bleret Valérie , Loly Catherine , Maquet Didier , Sartini Elena , Smrke Urška
Published: August 2021

Background

It is encouraging to see a substantial increase in individuals surviving cancer. Even more so since most of them will have a positive effect on society by returning to work. However, many cancer survivors have unmet needs, especially when it comes to improving their quality of life (QoL). Only few survivors are able to meet all of the recommendations regarding well-being and there is a body of evidence that cancer survivors’ needs often remain neglected from health policy and national cancer control plans. This increases the impact of inequalities in cancer care and adds a dangerous component to it. The inequalities affect the individual survivor, their career, along with their relatives and society as a whole. The current study will evaluate the impact of the use of big data analytics and artificial intelligence on the self-efficacy of participants following intervention supported by digital tools. The secondary endpoints include evaluation of the impact of patient trajectories (from retrospective data) and patient gathered health data on prediction and improved intervention against possible secondary disease or negative outcomes (e.g. late toxicities, fatal events).

Methods/design

The study is designed as a single-case experimental prospective study where each individual serves as its own control group with basal measurements obtained at the recruitment and subsequent measurements performed every 6 months during follow ups. The measurement will involve CASE-cancer, Patient Activation Measure and System Usability Scale. The study will involve 160 survivors (80 survivors of Breast Cancer and 80 survivors of Colorectal Cancer) from four countries, Belgium, Latvia, Slovenia, and Spain. The intervention will be implemented via a digital tool (mHealthApplication), collecting objective biomarkers (vital signs) and subjective biomarkers (PROs) with the support of a (embodied) conversational agent. Additionally, the Clinical Decision Support system (CDSS), including visualization of cohorts and trajectories will enable oncologists to personalize treatment for an efficient care plan and follow-up management.

Discussion

We expect that cancer survivors will significantly increase their self-efficacy following the personalized intervention supported by the m-HealthApplication compared to control measurements at recruitment. We expect to observe improvement in healthy habits, disease self-management and self-perceived QoL.

Trial registrationISRCTN97617326.https://doi.org/10.1186/ISRCTN97617326. Original Registration Date: 26/03/2021.