bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel deletion variant in TRAPPC2 causes spondyloepiphyseal dysplasia tarda in a five-generation Chinese family
Authors: Zhang Cai , Du Caiqi , Ye Juan , Ye Feng , Wang Renfa , Luo Xiaoping , Liang Yan
Published: May 2020

Background

Spondyloepiphyseal dysplasia tarda (SEDT) is a rare X-linked recessive inherited osteochondrodysplasia caused by mutations in the TRAPPC2 gene. It is clinically characterized by disproportionate short stature and early onset of degenerative osteoarthritis. Clinical diagnosis can be challenging due to the late-onset of the disease and lack of systemic metabolic abnomalites. Genetic diagnosis is critical in both early diagnosis and management of the disease. Here we reported a five-generation Chinese SEDT family and described the novel molecular findings.

Methods

Detailed family history and clinical data were collected. Genomic DNA was extracted from venous blood samples of family members. The exons of genes known to be associated with skeletal disorders were captured and deep sequenced. Variants were annotated by ANNOVAR and associated with multiple databases. Putative variants were confirmed by Sanger sequencing. The identified variant was classified according to the American College of Medical Genetics (ACMG) criteria.

Results

The proband was a 27-year-old Chinese male who presented with short-trunk short stature and joint pain. His radiographs showed platyspondyly with posterior humping, narrow hip-joint surfaces, and pelvic osteosclerosis. A pedigree analysis of 5 generations with 6 affected males revealed an X-linked recessive mode of inheritance. Affected males were diagnosed as SEDT according to the clinical and radiological features. Next-generation sequencing identified a novel variant of c.216_217del in the exon 4 of TRAPPC2 gene in the proband and other affected males. This variant resulted in the shift of reading frame and early termination of protein translation (p.S73Gfs*15). The mother and maternal female relatives of the proband were heterozygous carriers of the same variant, while no variations were detected in this gene of his father and other unaffected males. Based on the ACMG criteria, the novel c.216_217del variant of the TRAPPC2 gene was the pathogenic variant of this SEDT family.

Conclusion

In this study we identified the novel pathogenic variant of of c.216_217del in the gene of TRAPPC2 in this five-generation Chinese SEDT family. Our findings expand the clinical and molecular spectrum of SEDT and helps the genetic diagnosis of SEDT patients.
Effects of educational practices on the peritonitis risk in peritoneal dialysis: a retrospective cohort study with data from the French peritoneal Dialysis registry (RDPLF)
Authors: Bonnal Hélène , Bechade Clémence , Boyer Annabel , Lobbedez Thierry , Guillouët Sonia , Verger Christian , Ficheux Maxence , Lanot Antoine
Published: May 2020

Background

Peritoneal dialysis (PD) is a home-based therapy performed by patients or their relatives in numerous cases, and the role of patients’ educational practices in the risk of peritonitis is not well assessed. Our aim was to evaluate the effect of PD learning methods on the risk of peritonitis.

Methods

This was a retrospective multicentric study based on data from a French registry. All incident adults assisted by family or autonomous for PD exchanges in France between 2012 and 2015 were included. The event of interest was the occurrence of peritonitis. Cox and hurdle regression models were used for statistical analysis to asses for the survival free of peritonitis, and the risk of first and subsequent peritonitis.

Results

1035 patients were included. 967 (93%) received education from a specialized nurse. Written support was used for the PD learning in 907 (87%) patients, audio support in 221 (21%) patients, and an evaluation grid was used to assess the comprehension in 625 (60%) patients. In the “zero” part of the hurdle model, the use of a written support and starting PD learning with hands-on training alone were associated with a lower survival free of peritonitis (respectively HR 1.59, 95%CI 1.01–2.5 and HR 1.94, 95%CI 1.08–3.49), whereas in the “count” part, the use of an audio support and starting of PD learning with hands-on training in combination with theory were associated with a lower risk of presenting further episodes of peritonitis after a first episode (respectively HR 0.55, 95%CI 0.31–0.98 and HR 0.57, 95%CI 0.33–0.96).

Conclusions

The various PD education modalities were associated with differences in the risk of peritonitis. Prospective randomized trials are necessary to confirm causal effect. Caregivers should assess the patient’s preferred learning style and their literacy level and adjust the PD learning method to each individual.
Matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of multiple sclerosis: systematic review and meta-analysis
Authors: Mohammadhosayni Mina , Khosrojerdi Arezou , Lorian Keivan , Aslani Saeed , Imani Danyal , Razi Bahman , Babaie Farhad , Torkamandi Shahram
Published: May 2020

Background

Several studies have reported the association between polymorphisms in Matrix metalloproteinases (MMPs) gene family and risk of Multiple sclerosis (MS). However, the results have been inconsistent and inconclusive. To resolve this issue, here we performed a systematic review and meta-analysis of the MMP-91562 C/T (rs3918242), MMP-3 (− 1612 5A/6A), and MMP-2 (− 1306 C/T) polymorphisms and susceptibility to MS.

Methods

We conducted a comprehensive systematic search in the major electronic database, including Scopus and PubMed to look up for relevant studies published before December 2019 that surveyed the association between the MMP-91562 C/T (rs3918242), MMP-3 (− 1612 5A/6A), and MMP-2 (− 1306 C/T) polymorphisms and susceptibility to MS. The level of association between the polymorphisms and susceptibility to MS in the polled analysis was determined by calculating the odds ratio (OR) and the corresponding 95% confidence interval (CI).

Results

We found 15 studies containing 2430 MS subjects and 2304 controls. A statistically significant association was observed in the all five comparisons of the MMP-91562 C/T polymorphism and MS risk as follows: dominant model (OR = 1.62, 95% CI = 1.03–2.53, P = 0.03), recessive model (OR = 2.69, 95% CI = 1.68–4.29, P < 0.001), allelic model (OR = 1.51, 95% CI = 1–2.28, P = 0.04), TT vs. CC model (OR = 3.20, 95% CI = 1.87–5.46, P < 0.001), and CT vs. CC model (OR = 1.53, 95% CI = 1.02–2.28, P = 0.04).

Conclusions

Our meta-analysis revealed significant association of MMP-9 (− 1562 C/T) Single-nucleotide polymorphism (SNP) with MS susceptibility that increased the disease risk.
Antenatal testing for anaemia, HIV and syphilis in Indonesia – a health systems analysis of low coverage
Authors: Baker C. , Limato R. , Tumbelaka P. , Rewari B. B. , Nasir S. , Ahmed R. , Taegtmeyer M.
Published: May 2020

Background

Adverse pregnancy outcomes can be prevented through the early detection and treatment of anaemia, HIV and syphilis during the antenatal period. Rates of testing for anaemia, HIV and syphilis among women attending antenatal services in Indonesia are low, despite its mandate in national guidelines and international policy.

Methods

Midwife-held antenatal care records for 2015 from 8 villages in 2 sub-districts within Cianjur district were reviewed, alongside the available sub-district Puskesmas (Community Health Centre) maternity and laboratory records. We conducted four focus group discussions with kaders (community health workers) (n = 16) and midwives (n = 9), and 13 semi-structured interviews with laboratory and counselling, public sector maternity and HIV management and relevant non-governmental organisation staff. Participants were recruited from village, sub-district, district and national level as relevant to role.

Results

We were unable to find a single recorded result of antenatal testing for HIV, syphilis or anaemia in the village (566 women) or Puskesmas records (2816 women) for 2015. Laboratory records did not specifically identify antenatal women. Participants described conducting and reporting testing in a largely ad hoc manner; relying on referral to health facilities based on clinical suspicion or separate non-maternity voluntary counselling and testing programs. Participants recognized significant systematic challenges with key differences between the more acceptable (and reportedly more often implemented) haemoglobin testing and the less acceptable (and barely implemented) HIV and syphilis testing. However, a clear need for leadership and accountability emerged as an important factor for prioritizing antenatal testing and addressing these testing gaps.

Conclusions

Practical solutions such as revised registers, availability of point-of-care tests and capacity building of field staff will therefore need to be accompanied by both funding and political will to coordinate, prioritize and be accountable for testing in pregnancy.
Speculum versus digital insertion of Foley catheter for induction of labor in Nulliparas with unripe cervix: a randomized controlled trial
Authors: Chia Hang Min , Tan Peng Chiong , Tan Sze Ping , Hamdan Mukhri , Omar Siti Zawiah
Published: May 2020

Background

Induction of labor (IoL) is an increasingly common obstetric procedure. Foley catheter IoL is recommended by WHO. It is associated with the lowest rate of uterine hyperstimulation syndrome and similar duration to delivery and vaginal delivery rate compared to other methods. Insertion is typically via speculum but digital insertion has been reported to be faster, better tolerated and with similar universal insertion success compared to speculum insertion in a mixed population of nulliparas and multiparas. Transcervical procedure is more challenging in nulliparas and when the cervix is unripe. We evaluated the ease and tolerability of digital compared to speculum insertion of Foley catheter for induction of labor in nulliparas with unripe cervixes.

Methods

A randomized trial was performed in a university hospital in Malaysia. Participants were nulliparas at term with unripe cervixes (Bishop Score ≤ 5) admitted for IoL who were randomized to digital or speculum-aided transcervical Foley catheter insertion in lithotomy position. Primary outcomes were insertion duration, pain score [11-point Visual Numerical Rating Scale (VNRS)], and failure. All primary outcomes were recorded after the first insertion.

Results

Data from 86 participants were analysed. Insertion duration (with standard deviation) was 2.72 ± 1.85 vs. 2.25 ± 0.55 min p = 0.12, pain score (VNRS) median [interquartile range] 3.5 [2–5] vs. 3 [2–5] p = 0.72 and failure 2/42 (5%) vs. 0/44 (0%) p = 0.24 for digital vs speculum respectively. There was no significant difference found between the two groups for all three primary outcomes. Induction to delivery 30.7 ± 9.4 vs 29.6 ± 11.5 h p = 0.64, Cesarean section 25/60 (64%) vs 28/64 (60%) RR 0.9 95% CI p = 0.7 and maternal satisfaction VNRS score with the birth process 7 [IQR 6–8] vs 7 [7–8] p = 0.97 for digital vs. speculum arms respectively. Other labor, delivery and neonatal secondary outcomes were not significantly different.

Conclusion

Digital and speculum insertion in nulliparas with unripe cervixes had similar insertion performance. As digital insertion required less equipment and consumables, it could be the preferred insertion method for the equally adept and the insertion technique to train towards.

Trial registration

This trial was registered with ISRCTN registration number 13804902 on 15 November 2017.
Prognostic role of alpha-fetoprotein in patients with hepatocellular carcinoma treated with repeat transarterial chemoembolisation
Authors:   The Melbourne Liver Group, Mishra Gauri , Dev Anouk , Paul Eldho , Cheung Wa , Koukounaras Jim , Jhamb Ashu , Marginson Ben , Lim Beng Ghee , Simkin Paul , Borsaru Adina , Burnes James , Goodwin Mark , Ramachandra Vivek , Spanger Manfred , Lubel John , Gow Paul , Sood Siddharth , Thompson Alexander , Ryan Marno , Nicoll Amanda , Bell Sally , Majeed Ammar , Kemp William , Roberts Stuart K.
Published: May 2020

Background

Repeat transarterial chemoembolisation (rTACE) is often required for hepatocellular carcinoma (HCC) to achieve disease control, however, current practice guidelines regarding treatment allocation vary significantly. This study aims to identify key factors associated with patient survival following rTACE to facilitate treatment allocation and prognostic discussion.

Method

Patients with HCC undergoing rTACE at six Australian tertiary centers from 2009 to 2014 were included. Variables encompassing clinical, tumour, treatment type and response factors were analysed against the primary outcome of overall survival. Univariate analysis and multivariate Cox regression modelling were used to identify factors pre- and post-TACE therapy significantly associated with survival.

Results

Total of 292 consecutive patients underwent rTACE with mainly Child Pugh A cirrhosis (61%) and BCLC stage A (57%) disease. Median overall survival (OS) was 30 months (IQR 15.2–50.2) from initial TACE. On multivariate analysis greater tumour number (p = 0.02), higher serum bilirubin (p = 0.007) post initial TACE, and hepatic decompensation (p = 0.001) post second TACE were associated with reduced survival. Patients with serum AFP ≥ 200 ng/ml following initial TACE had lower survival (p = 0.001), compared to patients with serum AFP level that remained < 200 ng/ml post-initial TACE, with an overall survival of 19.4 months versus 34.7 months (p = 0.0001) respectively.

Conclusion

Serum AFP level following initial treatment in patients undergoing repeat TACE for HCC is a simple and useful clinical prognostic marker. Moreover, it has the potential to facilitate appropriate patient selection for rTACE particularly when used in conjunction with baseline tumour burden and severity of hepatic dysfunction post-initial TACE.
Transscleral cyclophotocoagulation followed by cataract surgery: a novel protocol to treat refractory acute primary angle closure
Authors: Liu Wei , Qin Luning , Xu Chenjia , Huang Dandan , Guo Ruru , Ji Jian , Jansonius Nomdo M.
Published: May 2020

Background

To introduce a novel protocol to treat refractory acute primary angle closure (APAC): transscleral cyclophotocoagulation (TCP) followed by cataract surgery.

Methods

Thirteen APAC eyes (13 patients) were enrolled in this prospective case series as study group. All patients underwent emergency TCP (20 pulses of 2000 mW during 2000 ms applied to the inferior quadrant) followed by scheduled cataract surgery. They were compared to 13 age- and gender-matched patients treated with emergency phacotrabeculectomy. We recorded intraocular pressure (IOP), best corrected visual acuity (BCVA), and complications, and several ultrasound biomicroscopy (UBM) parameters before and after TCP.

Results

In the study group, IOP decreased from 51.5 ± 7.0 mmHg (mean ± standard deviation) before TCP to 16.4 ± 5.4 mmHg 1 day after TCP (P < 0.001). At 6 months, there was no significant difference in IOP between the study group (14.0 ± 3.4 mmHg) and control group (16.7 ± 4.3 mmHg;P = 0.090); IOP lowering medications were used by 0/13 in the study group and 2/13 patients in the control group (P = 0.48). At 6 months, there was no significant difference in BCVA between the study group and the control group (20/25 (20/200 to 20/25) and 20/30 (20/50 to 20/25), respectively;P = 1.0). The UBM parameters anterior chamber depth (P = 0.016), angle-opening distance at 500 μm (P = 0.011), and maximum ciliary body thickness (P < 0.001) increased significantly while the iris-ciliary process distance decreased significantly (P = 0.020) after TCP.

Conclusions

TCP effectively lowers IOP and modifies the anterior chamber morphology in APAC; TCP followed by cataract surgery can be considered an alternative to treat refractory APAC but needs further evaluation.

Trial registration

This project was registered in Chinese Clinical Trial Registry (ChiCTR1800017475) at July, 31, 2018 (http://www.chictr.org.cn/edit.aspx?pid=29629&htm=4).
The role of social support and emotional exhaustion in the association between work-family conflict and anxiety symptoms among female medical staff: a moderated mediation model
Authors: Zhang Hui , Tang Leiwen , Ye ZhiHong , Zou Ping , Shao Jing , Wu Man , Zhang Qi , Qiao Guojin , Mu Shaoyu
Published: May 2020

Background

Limited work has been done to explain how work-family conflict is related to anxiety symptoms and the roles of emotional exhaustion and social support may play.

Methods

Based on a sample of 764 female nurses and physicians, a model was tested in which emotional exhaustion served as a mediator and social support was regarded as a moderator between work-family conflict and anxiety symptoms.

Results

This current study supported a moderated mediation model where the relationship between work-family conflict and anxiety symptoms via emotional exhaustion was weakest for female medical staff who reported high levels of social support.

Conclusions

This study contribute to providing an understanding of how and when work-family conflict affects anxiety symptoms. The results implicate a wide range of interventions aimed at promoting mental wellbeing among female medical staff for policymakers and individuals.
Perceived greenness at home and at university are independently associated with mental health
Authors: Loder Alexander K. F. , Schwerdtfeger A. R. , van Poppel Mireille N. M.
Published: May 2020

Background

Previous studies reported positive associations between perceived neighborhood greenness and mental health. There has been a focus on perceived neighborhood greenness at people’s home environment or in general, but data are lacking on greenness at working places or other locations where they actually spend most of their time during their day.

Methods

This study investigated the perceived greenness of college students’ home and study environments and its relation to mental health. An online survey collected data from 601 participants with a mean age of 24 years, living in or around and studying in the city of Graz, Austria. The perceived greenness at home and at university was assessed using questions on quality of and access to green space; mental health was measured with the WHO-5 well-being index. Uni- and multivariate regression analyses were used to analyze the data.

Results

The analyses revealed positive associations between perceived greenness at home and mental health as well as perceived greenness at university and mental health. This adds more evidence to the existing literature that perceiving the environment as green is positively related to better mental health.

Conclusions

Future research will have to incorporate objective greenness measures as a means of controlling for the reliability of the measurements and investigate the effects of different environments people are exposed to over the course of a day.
Recurrent pneumothorax and intrapulmonary cavitary lesions in a male patient with vascular Ehlers-Danlos syndrome and a novel missense mutation in the COL3A1 gene: a case report
Authors: Wan Tingting , Ye Jinyan , Wu Peiliang , Cheng Mengshi , Jiang Baihong , Wang Hailong , Li Jianmin , Ma Jun , Wang Liangxing , Huang Xiaoying
Published: May 2020

Background

Vascular Ehlers-Danlos syndrome (vEDS) is a rare autosomal dominant hereditary collagen disease caused by a defect or deficiency in the pro-α1 chain of type III procollagen encoded by the COL3A1 gene. Patients with vEDS rarely present with multiple pneumothoraces. The clinical features of this disease are not familiar to clinicians and are easily missed. We report a patient with a novel missense mutation in the COL3A1 gene (NM_000090.3: c.2977G > A) and hope to provide clinicians with valuable information.

Case presentation

We reported the case of a young man presenting with frequent episodes of pneumothorax and intrapulmonary cavities and nodular lesions without arterial or visceral complications. His skin was thin and transparent, and the joints were slightly hypermobile. Whole-exome sequencing (chip capture high-throughput sequencing) revealed a heterozygous missense mutation in exon 41 of the COL3A1 gene (NM_000090.3: c.2977G > A), confirming the diagnosis of vEDS. vEDS remains a very rare and difficult diagnosis to determine.

Conclusion

When a patient presents with recurrent pneumothorax, intrapulmonary cavities and nodular lesions, thin and transparent skin, and hypermobile joints, clinicians should consider the diagnosis of vEDS.
Lumbar plain radiograph is not reliable to identify lumbosacral transitional vertebra types according to Castellvi classification principle
Authors: Hou Lisheng , Bai Xuedong , Li Haifeng , Gao Tianjun , Li Wei , Wen Tianyong , He Qing , Ruan Dike , Shi Lijing , Bing Wei
Published: May 2020

Background

The anteroposterior view of the lumbar plain radiograph (AP-LPR) was chosen as the original and first radiographic tool to determine and classify lumbosacral transitional vertebra with morphological abnormality (MA-LSTV) according to the Castellvi classification. However, recent studies found that AP-LPR might not be sufficient to detect or classify MA-LSTV correctly. The present study aims to verify the reliability of AP-LPR on detecting and classifying MA-LSTV types, taking coronal reconstructed CT images (CT-CRIs) as the gold criteria.

Methods

Patients with suspected MA-LSTVs determined by AP-LPR were initially enrolled. Among them, those who received CT-CRIs were formally enrolled to verify the sensitivity of AP-LPR on detecting and classifying MA-LSTV types according to the Castellvi classification principle.

Results

A total of 298 cases were initially enrolled as suspected MA-LSTV, among which 91 cases who received CT-CRIs were enrolled into the final study group. All suspected MA-LSTVs were verified to be real MA-LSTVs by CT-CRIs. However, 35.2% of the suspected MA-LSTV types judged by AP-LPR were not consistent with the final types judged by CT-CRIs. Two suspected type IIIa and 20 suspected type IIIb MA-LSTVs were verified to be true, while 9 of 39 suspected type IIa, 9 and 3 of 17 suspected type IIb, and 11 of 13 suspected type IV MA-LSTVs were verified to truly be type IIIa, IIIb, IV and IIIb MA-LSTVs by CT-CRIs, respectively. Incomplete joint-like structure (JLS) or bony union structure (BUS) and remnants of sclerotic band (RSB) between the transverse process (TP) and sacrum were considered to be the main reasons for misclassification.

Conclusion

Although AP-LPR could correctly detect MA-LSTV, it could not give accurate type classification. CT-CRIs could provide detailed information between the TP and sacrum area and could be taken as the gold standard to detect and classify MA-LSTV.
Taking care of our future doctors: a service evaluation of a medical student mental health service
Authors: Jacob Rebecca , Li Tsz-yan , Martin Zoe , Burren Amanda , Watson Peter , Kant Rhian , Davies Richard , Wood Diana F.
Published: May 2020

Background

Studies suggest medical students experience high levels of mental distress during training but are less likely, than other students, to access care due to stigma and concerns regarding career progression. In response, The School of Clinical Medicine, University of Cambridge supported the development of the ‘Clinical Student Mental Health Service’ to provide specialist input for this vulnerable group. This study evaluates the efficiency and effectiveness of this service.

Methods

Using mixed-methods, cross-sectional analysis of validated psychiatric rating scales and qualitative feedback, 89 responses were analysed from 143 clinical students referred, between 2015 and 2019. The care pathway included initial review by a psychiatrist, who triaged students to psychologists delivering therapies including: Cognitive Behavioural Therapy, Interpersonal Therapy, Eye Movement Desensitization Reprocessing Therapy or Cognitive Analytic Therapy.

Efficiency was assessed by waiting times for psychiatry and psychology interventions, and number of sessions. Academic outcomes included school intermission and graduation. Clinical effectiveness was analysed by measuring global distress, depression, anxiety, functioning and suicidal risk. Pre/post intervention changes were captured using t-test and McNemar test with thematic analysis of qualitative feedback.

Results

Referral rates increased from 3.93% (22/560) in 2015 to 6.74% (45/668) in 2018. Median waiting times for initial psychiatric assessment and start of therapy was 26 and 33 days, respectively. All graduating students moved on to work as junior doctors.

Levels of distress, (t = 7.73, p < 0.001, df = 31), depression (t = 7.26, p < 0.001, df = 34) anxiety (Z = − 4.63, p < 0.001) and suicide risk (Z = − 3.89, p < 0.001) were significantly reduced. Participant’s functioning was significantly improved (p < 0.001, 99.5% CI 4.55 to 14.62). Feedback indicated high satisfaction with the rapid access and flexibility of the service and the team clinicians.

Conclusions

A significant proportion of medical students attending the service scored highly on validated rating scales measuring emotional distress, suicidality and mental illness. Reassuringly they benefitted from timely specialist mental health input, showing improvements in mental well-being and improved functioning. The development and design of this service might serve as an exemplar for medical schools developing similar support for their students.
Differential expression of hemolysin genes in weakly and strongly hemolytic Brachyspira hyodysenteriae strains
Authors: Joerling Jessica , Willems Hermann , Ewers Christa , Herbst Werner
Published: May 2020

Background

Swine dysentery (SD) is a diarrheal disease in fattening pigs that is caused by the strongly hemolytic speciesBrachyspira(B.)hyodysenteriae, B. hampsoniiandB. suanatina.As weakly hemolyticBrachyspiraspp. are considered less virulent or even non-pathogenic, the hemolysin is regarded as an important factor in the pathogenesis of SD. Four hemolysin genes (tlyA, tlyB, tlyC,andhlyA) and four putative hemolysin genes (hemolysin,hemolysin activation protein,hemolysin III, andhemolysin channel protein) have been reported, but their role in strong hemolysis is not entirely clear. Our study aimed to assess the transcriptional activity of eight (putative) hemolysin genes in a strongly hemolytic (B204) and a weakly hemolytic (G423)B. hyodysenteriaestrain during non-hemolytic and hemolytic growth stages.

Results

Strongly and weakly hemolyticB. hyodysenteriaestrains caused hemolysis on blood agar at different growth stages, namely during log phase (B204) and stationary/death phase (G423). During the lag, early log, late log (stationary phase in G423) and death phase (time points 1–4) strains differed in their hemolysin gene transcription patterns. At time point 1, transcription of the putativehemolysingene was higher in B204 than in G423. At time point 2,tlyAandtlyCwere upregulated in B204 during hemolysis.TlyBandhlyAwere upregulated in both strains at all time points, but higher transcription rates were observed in the weakly hemolytic strain G423. The transcription activity of thehemolysin channel proteingene was quite similar in both strains, whereas thehemolysin activation proteingene was upregulated in the non-hemolytic stage of B204 at time point 4. Sequence analysis revealed deletions, insertions and single nucleotide polymorphisms in the G423hlyApromoter, although without altering the transcription activity of this gene.

Conclusion

Our data indicate a combined activity of TlyA and TlyC as the most probable underlying mechanism of strong hemolysis inB. hyodysenteriae. Further studies should verify if the expression oftlyAis upregulated by the putativehemolysingene. Depending on their immunogenic potential TlyA and TlyC may serve as possible vaccine candidates, especially since vaccines for an effective control of swine dysentery are currently not available.
Escherichia coli metabolism under short-term repetitive substrate dynamics: adaptation and trade-offs
Authors: Vasilakou Eleni , van Loosdrecht Mark C. M. , Wahl S. Aljoscha
Published: May 2020

Background

Microbial metabolism is highly dependent on the environmental conditions. Especially, the substrate concentration, as well as oxygen availability, determine the metabolic rates. In large-scale bioreactors, microorganisms encounter dynamic conditions in substrate and oxygen availability (mixing limitations), which influence their metabolism and subsequently their physiology. Earlier, single substrate pulse experiments were not able to explain the observed physiological changes generated under large-scale industrial fermentation conditions.

Results

In this study we applied a repetitive feast–famine regime in an aerobicEscherichia coliculture in a time-scale of seconds. The regime was applied for several generations, allowing cells to adapt to the (repetitive) dynamic environment. The observed response was highly reproducible over the cycles, indicating that cells were indeed fully adapted to the regime. We observed an increase of the specific substrate and oxygen consumption (average) rates during the feast–famine regime, compared to a steady-state (chemostat) reference environment. The increased rates at same (average) growth rate led to a reduced biomass yield (30% lower). Interestingly, this drop was not followed by increased by-product formation, pointing to the existence of energy-spilling reactions. During the feast–famine cycle, the cells rapidly increased their uptake rate. Within 10 s after the beginning of the feeding, the substrate uptake rate was higher (4.68 μmol/gCDW/s) than reported during batch growth (3.3 μmol/gCDW/s). The high uptake led to an accumulation of several intracellular metabolites, during the feast phase, accounting for up to 34% of the carbon supplied. Although the metabolite concentrations changed rapidly, the cellular energy charge remained unaffected, suggesting well-controlled balance between ATP producing and ATP consuming reactions.

Conclusions

The adaptation of the physiology and metabolism ofE. coliunder substrate dynamics, representative for large-scale fermenters, revealed the existence of several cellular mechanisms coping with stress. Changes in the substrate uptake system, storage potential and energy-spilling processes resulted to be of great importance. These metabolic strategies consist a meaningful step to further tackle reduced microbial performance, observed under large-scale cultivations.
RETRACTED ARTICLE: The novel long non-coding RNA LATS2-AS1-001 inhibits gastric cancer progression by regulating the LATS2/YAP1 signaling pathway via binding to EZH2
Authors: Sun Dan , Wang Ying , Wang Huan , Xin Yan
Published: May 2020

Background

To explore the expression pattern and role of the novel long non-coding RNA LATS2 antisense transcript 1 (LATS2-AS1-001) in gastric cancer (GC).

Methods

qRT-PCR was applied to evaluate LATS2-AS1-001 expression and correlation with LATS2 in GC. In vitro experiments were performed to investigate the role of LATS2-AS1-001 in GC cells. RNA immunoprecipitation (RIP) was performed to assess the interaction between EZH2 and LATS2-AS1-001. LATS2/YAP1 signaling pathway proteins were detected by immunoblot. Oncomine and KMPLOT data analysis was conducted to assess the prognostic value of YAP1 in GC.

Results

Decreased expression levels of LATS2-AS1-001 and LATS2 were confirmed in 357 GC tissues compared with the normal mucosa. A strong positive correlation between LATS2-AS1-001 and LATS mRNA expression was found in Pearson Correlation analysis (r = 0.719, P < 0.001). Furthermore, ROC curve analysis revealed areas under the curves for LATS2-AS1-001 and LATS2 of 0.7274 and 0.6865, respectively (P < 0.001), which indicated that LATS2-AS1-001 and LATS could be used as diagnostic indicators in GC. Moreover, ectopic expression of LATS2-AS1-001 decreased cell viability, induced G0/G1 phase arrest, and inhibited cell migration and invasion in GC cells. Mechanistically, overexpressing LATS2-AS1-001 upregulated LATS2 and induced YAP1 phosphorylation via binding to EZH2. Oncomine and KMPLOT database analysis demonstrated YAP1 was highly expressed in human GC samples, and high YAP1 expression predicted poor patient prognosis in GC.

Conclusion

This study revealed that lncRNA LATS2-AS1-001 might serve as a potential diagnostic index in GC and act as a suppressor of GC progression.
Automated computer-assisted detection system for cerebral aneurysms in time-of-flight magnetic resonance angiography using fully convolutional network
Authors: Chen Geng , Wei Xia , Lei Huang , Liqin Yang , Yuxin Li , Yakang Dai , Daoying Geng
Published: May 2020

Background

As the rupture of cerebral aneurysm may lead to fatal results, early detection of unruptured aneurysms may save lives. At present, the contrast-unenhanced time-of-flight magnetic resonance angiography is one of the most commonly used methods for screening aneurysms. The computer-assisted detection system for cerebral aneurysms can help clinicians improve the accuracy of aneurysm diagnosis. As fully convolutional network could classify the image pixel-wise, its three-dimensional implementation is highly suitable for the classification of the vascular structure. However, because the volume of blood vessels in the image is relatively small, 3D convolutional neural network does not work well for blood vessels.

Results

The presented study developed a computer-assisted detection system for cerebral aneurysms in the contrast-unenhanced time-of-flight magnetic resonance angiography image. The system first extracts the volume of interest with a fully automatic vessel segmentation algorithm, then uses 3D-UNet-based fully convolutional network to detect the aneurysm areas. A total of 131 magnetic resonance angiography image data are used in this study, among which 76 are training sets, 20 are internal test sets and 35 are external test sets. The presented system obtained 94.4% sensitivity in the fivefold cross-validation of the internal test sets and obtained 82.9% sensitivity with 0.86 false positive/case in the detection of the external test sets.

Conclusions

The proposed computer-assisted detection system can automatically detect the suspected aneurysm areas in contrast-unenhanced time-of-flight magnetic resonance angiography images. It can be used for aneurysm screening in the daily physical examination.
Spatial predictive properties of built environment characteristics assessed by drop-and-spin virtual neighborhood auditing
Authors: Plascak Jesse J. , Schootman Mario , Rundle Andrew G. , Xing Cathleen , Llanos Adana A. M. , Stroup Antoinette M. , Mooney Stephen J.
Published: May 2020

Background

Virtual neighborhood audits have been used to visually assess characteristics of the built environment for health research. Few studies have investigated spatial predictive properties of audit item responses patterns, which are important for sampling efficiency and audit item selection. We investigated the spatial properties, with a focus on predictive accuracy, of 31 individual audit items related to built environment in a major Metropolitan region of the Northeast United States.

Methods

Approximately 8000 Google Street View (GSV) scenes were assessed using the CANVAS virtual audit tool. Eleven trained raters audited the 360°view of each GSV scene for 10 sidewalk-, 10 intersection-, and 11 neighborhood physical disorder-related characteristics. Nested semivariograms and regression Kriging were used to investigate the presence and influence of both large- and small-spatial scale relationships as well as the role of rater variability on audit item spatial properties (measurement error, spatial autocorrelation, prediction accuracy). Receiver Operator Curve (ROC) Area Under the Curve (AUC) based on cross-validated spatial models summarized overall predictive accuracy. Correlations between predicted audit item responses and select demographic, economic, and housing characteristics were investigated.

Results

Prediction accuracy was better within spatial models of all items accounting for both small-scale and large- spatial scale variation (vs large-scale only), and further improved with additional adjustment for rater in a majority of modeled items. Spatial predictive accuracy was considered ‘Excellent’ (0.8 ≤ ROC AUC < 0.9) for full models of all but four items. Predictive accuracy was highest and improved the most with rater adjustment for neighborhood physical disorder-related items. The largest gains in predictive accuracy comparing large- + small-scale to large-scale only models were among intersection- and sidewalk-items. Predicted responses to neighborhood physical disorder-related items correlated strongly with one another and were also strongly correlated with racial-ethnic composition, socioeconomic indicators, and residential mobility.

Conclusions

Audits of sidewalk and intersection characteristics exhibit pronounced variability, requiring more spatially dense samples than neighborhood physical disorder audits do for equivalent accuracy. Incorporating rater effects into spatial models improves predictive accuracy especially among neighborhood physical disorder-related items.
Gender-based vulnerability: combining Pareto ranking and spatial statistics to model gender-based vulnerability in Rohingya refugee settlements in Bangladesh
Authors: Nelson Erica L. , Saade Daniela Reyes , Gregg Greenough P.
Published: May 2020

Background

The Rohingya refugee crisis in Bangladesh continues to outstrip humanitarian resources and undermine the health and security of over 900,000 people. Spatial, sector-specific information is required to better understand the needs of vulnerable populations, such as women and girls, and to target interventions with improved efficiency and effectiveness. This study aimed to create a gender-based vulnerability index and explore the geospatial and thematic variations in gender-based vulnerability of Rohingya refugees residing in Bangladesh by utilizing pre-existing, open source data.

Methods

Data sources included remotely-sensed REACH data on humanitarian infrastructure, United Nations Population Fund resource availability data, and the Needs and Population Monitoring Survey conducted by the International Organization for Migration in October 2017. Data gaps were addressed through probabilistic interpolation. A vulnerability index was designed through a process of literature review, variable selection and thematic grouping, normalization, and scorecard creation, and Pareto ranking was employed to rank sites based on vulnerability scoring. Spatial autocorrelation of vulnerability was analyzed with the Global and Anselin Local Moran’s I applied to both combined vulnerability index rank and disaggregated thematic ranking.

Results

Of the settlements, 24.1% were ranked as ‘most vulnerable,’ with 30 highly vulnerable clusters identified predominantly in the northwest region of metropolitan Cox’s Bazar. Five settlements in Dhokkin, Somitapara, and Pahartoli were categorized as less vulnerable outliers amongst highly vulnerable neighboring sites. Security- and health-related variables appear to be the most significant drivers of gender-specific vulnerability in Cox’s Bazar. Clusters of low security and education vulnerability measures are shown near Kutupalong.

Conclusion

The humanitarian sector produces tremendous amounts of data that can be analyzed with spatial statistics to improve research targeting and programmatic intervention. The critical utilization of these data and the validation of vulnerability indexes are required to improve the international response to the global refugee crisis. This study presents a novel methodology that can be utilized to not only spatially characterize gender-based vulnerability in refugee populations, but can also be calibrated to identify and serve other vulnerable populations during crises.
A systematic review of studies measuring health-related quality of life of general injury populations: update 2010–2018
Authors: Geraerds A. J. L. M. , Richardson Amy , Haagsma Juanita , Derrett Sarah , Polinder Suzanne
Published: May 2020

Background

Studies examining the impact of injury on health-related quality of life (HRQL) over time are necessary to understand the short- and long-term consequences of injury for population health. The aim of this systematic review was to provide an evidence update on studies that have measured HRQL over time in general injury populations using a generic (general) health state measure.

Methods

Studies conducted between 2010 and 2018 that assessed HRQL at more than one time point among general injury populations were eligible for inclusion. Two reviewers independently extracted information from each study on design, HRQL measure used, method of HRQL measure administration, timing of assessment(s), predictive variables, ability to detect change, and findings. Quality appraisals of each study were also completed by two reviewers using items from the RTI Item Bank on Risk of Bias and Precision of Observational Studies and the Guidelines for the Conduction of Follow-up Studies Measuring Injury-Related Disability.

Results

Twenty-nine studies (44 articles) that met the inclusion criteria were identified. HRQL was measured using 14 different generic measures; the SF-36, SF-12, and EQ-5D were used most frequently. A varying number of follow-up assessments were undertaken, ranging from one to five. Follow-up often occurred 12 months post-injury. Fewer studies (n = 11) examined outcomes two or more years post-injury, and only one to 10 years post-injury. While most studies documented improvements in HRQL over time since the injury event, study populations had not returned to pre-injury status or reached general population norm HRQL values at post-injury follow-ups.

Conclusions

Since 2010 there has been a substantial increase in the number of studies evaluating the HRQL of general injury populations. However, significant variability in study design continues to impede quantification of the impact of injury on population health over time. Variation between studies is particularly evident with respect to timing and number of follow-up assessments, and selection of instruments to evaluate HRQL.
Reimagining the role of the nursing workforce in Uganda after more than a decade of ART scale-up
Authors: Zakumumpa Henry
Published: May 2020

Background

The expanding roles and increasing importance of the nursing workforce in health services delivery in resource-limited settings is not adequately documented and sufficiently recognized in the current literature. Drawing upon the theme of 2020 as the International Year of the Nurse and the Midwife, we set out to describe how the role of nurses expanded tremendously in health facilities in Uganda during the era of anti-retroviral therapy (ART) scale-up that commenced in June 2004.

Methods

We employed a mixed-methods sequential explanatory research design. Phase I entailed a cross-sectional health facility survey (n= 195) to assess the extent to which human resource management strategies (such as task shifting) were common. Phase II entailed a qualitative multiple case study of 16 (of the 195) health facilities for an in-depth understanding of the strategies adopted (e.g. nurse-centred HIV care). Descriptive analyses were performed in STATA (v 13) while qualitative data were analysed by thematic approach.

Results

We found that nurses were the most represented cadre of health workers involved in the overall leadership of HIV clinics across Uganda. Most nurse-led HIV clinics were based in rural settings; however, this trend was fairly even across setting (rural/urban/peri-urban). While 181 (93%) health facilities allowed non-physician cadre to prescribe ART, a number of health facilities (n= 36) or 18% deliberately adoptednurse-ledHIV care models. Nurses were empowered to be multi-skilled with a wide range of competencies across the HIV care continuum right from HIV testing to mainstream clinical HIV disease management. In several facilities, nursing cadre were the backbone of ART service delivery. A select number of facilities devised differentiated models of task shifting from physicians to nurses in which the latter handled patients who were stable on ART.

Conclusion

Overall, our study reveals a wide expansion in the scope-of-practice of nurses during ART scale-up in Uganda. Nurses were thrust in roles of HIV disease management that were traditionally the preserve of physicians. Our study underscores the importance of reforming regulatory frameworks governing nursing workforce scope of practice such as the need for developing a policy on task shifting which is currently lacking in Uganda.
Leadership of the ultimate interdisciplinary team: Rehabilitation science at NIH
Authors: Cernich Alison N.
Published: May 2020

Background

Support for rehabilitation research at the National Institutes of Health (NIH) is robust and evolving. Since the time of its Blue Ribbon Panel on Rehabilitation Research, NIH has participated in several initiatives to coordinate the science and advance the field.

Discussion

Collaborative teams must continue to address key limitations in the field, including the desire for broad application of rehabilitation interventions, the need for basic science and translational research, the support of clinical trials and standard approaches, and the integration of technology.

Conclusion

Rehabilitation medicine is poised for critical advancements if interdisciplinary teams continue to work collaboratively to understand and address the needs of people with temporary or permanent functional limitations.
Insight into norcantharidin, a small-molecule synthetic compound with potential multi-target anticancer activities
Authors: Pan Mu-Su , Cao Jin , Fan Yue-Zu
Published: May 2020

Norcantharidin (NCTD) is a demethylated derivative of cantharidin, which is an anticancer active ingredient of traditional Chinese medicine, and is currently used clinically as a routine anti-cancer drug in China. Clarifying the anticancer effect and molecular mechanism of NCTD is critical for its clinical application. Here, we summarized the physiological, chemical, pharmacokinetic characteristics and clinical applications of NCTD. Besides, we mainly focus on its potential multi-target anticancer activities and underlying mechanisms, and discuss the problems existing in clinical application and scientific research of NCTD, so as to provide a potential anticancer therapeutic agent for human malignant tumors.
Clozapine generates obsessive compulsive disorder-like behavior in mice
Authors: Kang Shinwon , Noh Hyun Jong , Bae Soo Hyeon , Kim Yong-Seok , Lew Hogun , Lim Jisoo , Kim Se Joo , Hong Kyung Sue , Rah Jong-Cheol , Kim Chul Hoon
Published: May 2020

Clozapine is thought to induce obsessive compulsive symptoms (OCS) in schizophrenic patients. However, because OCS are often comorbid with schizophrenia regardless of clozapine treatment, it remains unclear whether clozapine can generate OCS de novo. Thus, it has been difficult to establish a causal link between clozapine and OCS in human studies. To address this question, we asked whether chronic treatment with clozapine can induce obsessive compulsive disorder (OCD)-like behavior in mice. We injected mice with long-term continuous release pellets embedded with clozapine four times at 60-day intervals and then monitored the mice for signs of OCD-like behavior up to 40 wk. of age. We found clozapine increases grooming behavior as early as 30 wk. of age. We also investigated the effect clozapine on grooming behavior in Sapap3 knockout (KO) mice, which are a well-known animal model of OCD. In Sapap3 heterozygous KO mice, clozapine increases grooming behavior much earlier than in wild-type mice, suggesting a clozapine-OCD gene interaction. Fluoxetine, which is often used in the treatment of OCS and OCD, reduced the grooming behavior induced by clozapine. These data demonstrate that chronic clozapine treatment can generate OCD-like behavior in mice and support the hypothesis that clozapine produces de novo OCS regardless of schizophrenia status.