bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conserved residues in the wheat (Triticum aestivum) NAM-A1 NAC domain are required for protein binding and when mutated lead to delayed peduncle and flag leaf senescence
Authors: Harrington Sophie A. , Overend Lauren E. , Cobo Nicolas , Borrill Philippa , Uauy Cristobal 
Published: September 2019

Abstract

Background
NAC transcription factors contain five highly conserved subdomains which are required for protein dimerisation and DNA binding. Few residues within these subdomains have been identified as essential for protein function, and fewer still have been shown to be of biological relevance in planta. Here we use a positive regulator of senescence in wheat, NAM-A1, to test the impact of missense mutations at specific, highly conserved residues of the NAC domain on protein function.

Results
We identified missense mutations in five highly conserved residues of the NAC domain of NAM-A1 in a tetraploid TILLING population. TILLING lines containing these mutations, alongside synonymous and non-conserved mutation controls, were grown under glasshouse conditions and scored for senescence. Four of the five mutations showed a significant and consistent delay in peduncle senescence but had no consistent effects on flag leaf senescence. All four mutant alleles with the delayed senescence phenotype also lost the ability to interact with the homoeolog NAM-B1 in a yeast two-hybrid assay. Two of these residues were previously shown to be involved in NAC domain function in Arabidopsis, suggesting conservation of residue function between species. Three of these four alleles led to an attenuated cell death response compared to wild-type NAM-A1 when transiently over-expressed in Nicotiana benthamiana. One of these mutations was further tested under field conditions, in which there was a significant and consistent delay in both peduncle and leaf senescence.

Conclusions
We combined field and glasshouse studies of a series of mutant alleles with biochemical analyses to identify four residues of the NAC domain which are required for NAM-A1 function and protein interaction. We show that mutations in these residues lead to a gradient of phenotypes, raising the possibility of developing allelic series of mutations for traits of agronomic importance. We also show that mutations in NAM-A1 more severely impact peduncle senescence, compared to the more commonly studied flag leaf senescence, highlighting this as an area deserving of further study. The results from this integrated approach provide strong evidence that conserved residues within the functional domains of NAC transcription factors have biological significance in planta.
Health systems readiness to provide geriatric friendly care services in Uganda: a cross-sectional study
Authors: Ssensamba Jude Thaddeus , Mukuru Moses , Nakafeero Mary , Ssenyonga Ronald , Kiwanuka Suzanne N. 
Published: September 2019

Abstract

Background
As ageing emerges as the next public health threat in Africa, there is a paucity of information on how prepared its health systems are to provide geriatric friendly care services. In this study, we explored the readiness of Uganda’s public health system to offer geriatric friendly care services in Southern Central Uganda.

Methods
Four districts with the highest proportion of old persons in Southern Central Uganda were purposively selected, and a cross-section of 18 randomly selected health facilities (HFs) were visited and assessed for availability of critical items deemed important for provision of geriatric friendly services; as derived from World Health Organization’s Age-friendly primary health care centres toolkit. Data was collected using an adapted health facility geriatric assessment tool, entered into Epi-data software and analysed using STATA version 14. Kruskal-Wallis and Dunn’s post hoc tests were conducted to determine any associations between readiness, health facility level, and district.

Results
The overall readiness index was 16.92 (SD ±4.19) (range 10.8–26.6). This differed across districts; Lwengo 17.91 (SD ±3.15), Rakai 17.63 (SD ±4.55), Bukomansimbi 16.51 (SD ±7.18), Kalungu 13.74 (SD ±2.56) and facility levels; Hospitals 26.62, Health centers four (HCIV) 20.05 and Health centers three (HCIII) 14.80. Low readiness was due to poor scores concerning; leadership (0%), financing (0%), human resources (1.7%) and health management information systems (HMIS) (11.8%) WHO building blocks. Higher-level HFs were statistically significantly friendlier than lower-level HFs (p = 0.015). The difference in readiness between HCIIIs and HCIVs was 2.39 (p = 0.025).

Conclusion
There is a low readiness for public health facilities to provide geriatric friendly care services in Uganda. This is due to gaps in all of the health system building blocks. There is a need for health system reforms in Uganda to adequately cater for service provision for older adults if the 2020 global healthy ageing goal is to be met.
Use of a mobile application for Ebola contact tracing and monitoring in northern Sierra Leone: a proof-of-concept study
Authors: Danquah Lisa O. , Hasham Nadia , MacFarlane Matthew , Conteh Fatu E. , Momoh Fatoma , Tedesco Andrew A. , Jambai Amara , Ross David A. , Weiss Helen A. 
Published: September 2019

Abstract

Background
The 2014–2016 Ebola epidemic in West Africa was the largest Ebola epidemic to date. Contact tracing was a core surveillance activity. Challenges with paper-based contact tracing systems include incomplete identification of contacts, delays in communication and response, loss of contact lists, inadequate data collection and transcription errors.
The aim of this study was to design and evaluate an electronic system for tracing contacts of Ebola cases in Port Loko District, Sierra Leone, and to compare this with the existing paper-based system. The electronic system featured data capture using a smartphone application, linked to an alert system to notify the District Ebola Response Centre of symptomatic contacts.

Methods
The intervention was a customised three-tier smartphone application developed using Dimagi’s CommCare platform known as the Ebola Contact Tracing application (ECT app). Eligible study participants were all 26 Contact Tracing Coordinators (CTCs) and 86 Contact Tracers (CTs) working in the 11 Chiefdoms of Port Loko District during the study period (April–August 2015). Case detection was from 13th April to 17th July 2015. The CTCs and their CTs were provided with smartphones installed with the ECT app which was used to conduct contact tracing activities. Completeness and timeliness of contact tracing using the app were compared with data from April 13th-June 7th 2015, when the standard paper-based system was used.

Results
For 25 laboratory-confirmed cases for whom paper-based contact tracing was conducted, data for only 39% of 408 contacts were returned to the District, and data were often incomplete. For 16 cases for whom app-based contact tracing was conducted, 63% of 556 contacts were recorded as having been visited on the app, and the median recorded duration from case confirmation to first contact visit was 70 h.

Conclusion
There were considerable challenges to conducting high-quality contact tracing in this setting using either the paper-based or the app-based system. However, the study demonstrated that it was possible to implement mobile health (mHealth) in this emergency setting. The app had the benefits of improved data completeness, storage and accuracy, but the challenges of using an app in this setting and epidemic context were substantial.
Rapid development of HIV elite control in a patient with acute infection
Authors: Morley Deirdre , Lambert John S. , Hogan Louise E. , De Gascun Cillian , Redmond Niamh , Rutishauser Rachel L. , Thanh Cassandra , Gibson Erica A. , Hobbs Kristen , Bakkour Sonia , Busch Michael P. , Farrell Jeremy , McGetrick Padraig , Henrich Timothy J. 
Published: September 2019

Abstract

Background
Elite controllers (EC), a small subset of the HIV-positive population (< 1%), suppress HIV viremia below the limit of quantification of clinical viral load assays in the absence of antiretroviral therapy (ART). However, there is a paucity of longitudinal data detailing the viral and immune dynamics or HIV reservoir seeding during acute infection in individuals that go on to become Elite Controllers.

Case presentation
In this report, we describe a case of a 42 year old woman diagnosed during acute infection who rapidly and permanently suppressed her viremia in the absence of antiretroviral therapy (ART). Rapid antibody/antigen testing was either negative or equivocal during acute infection, despite subsequent viral load testing at that time point with 71,550 plasma HIV RNA copies/mL, making initial diagnosis challenging. The patient subsequently developed detectable anti-HIV antibodies and an increase in HIV-specific CD8+ T cell responses to overlapping subtype C HIV gag peptide; very low-level plasma viremia (0.84 RNA copies/mL) was detected by an ultrasensitive assay 2 years following infection. Subsequently, she was started on ART for multifocal furunculosis despite continued suppression of virus and stable CD4+ T cell counts. Following ART initiation, CD8+ T cell responses increased, but no HIV DNA or RNA was able to be isolated from large numbers of peripheral blood CD4+ T cells.

Conclusion
This case provides important information regarding the establishment of elite HIV control during acute infection and also demonstrates an increase in HIV-specific immune responses following ART despite undetectable peripheral blood cellular measures of HIV persistence. This case also highlights the challenges in diagnosing acute HIV infection without the use of viral load testing in this rare elite controller phenotype.
Intensive phase treatment outcome and associated factors among patients treated for multi drug resistant tuberculosis in Ethiopia: a retrospective cohort study
Authors: Molie Teklu , Teklemariam Zelalem , Klinkenberg Eveline , Dessie Yadeta , Kumsa Andargachew , Mohammed Hussen , Debebe Adisalem , Assefa Dawit , Habte Abebe , Bedru Ahmed , Fiseha Daniel , Seyoum Berhanu 
Published: September 2019

Abstract

Background
Multi-drug resistant Tuberculosis (MDR-TB) is a strain of Mycobacterium tuberculosis that is resistant to at least Rifampicin and Isoniazid drugs. The treatment success rate for MDR-TB cases is lower than for drug susceptible TB. Globally only 55% of MDR-TB patients were successfully treated. Monitoring the early treatment outcome and better understanding of the specific reasons for early unfavorable and unknown treatment outcome is crucial for preventing the emergence of further drug-resistant tuberculosis. However, this information is scarce in Ethiopia. Therefore, this study aimed to determine the intensive phase treatment outcome and contributing factors among patients treated for MDR-TB in Ethiopia.

Methods
A 6 year retrospective cohort record review was conducted in fourteen TICs all over the country. The records of 751 MDR-TB patients were randomly selected using simple random sampling technique. Data were collected using a pre-tested and structured checklist. Multivariable multinomial logistic regression was undertaken to identify the contributing factors.

Results
At the end of the intensive phase, 17.3% of MDR-TB patients had an unfavorable treatment outcome, while 16.8% had an unknown outcome with the remaining having a favorable outcome. The median duration of the intensive phase was 9.0 months (IQR 8.04–10.54). Having an unfavorable intensive phase treatment outcome was found significantly more common among older age [ARRR = 1.047, 95% CI (1.024, 1.072)] and those with a history of hypokalemia [ARRR = 0.512, 95% CI (0.280, 0.939)]. Having an unknown intensive phase treatment outcome was found to be more common among those treated under the ambulatory care [ARRR = 3.2, 95% CI (1.6, 6.2)], rural dwellers [ARRR = 0.370, 95% CI (0.199, 0.66)], those without a treatment supporter [ARRR = 0.022, 95% CI (0.002, 0.231)], and those with resistance to a limited number of drugs.

Conclusion
We observed a higher rate of unfavorable and unknown treatment outcome in this study. To improve favorable treatment outcome more emphasis should be given to conducting all scheduled laboratory monitoring tests, assignment of treatment supporters for each patient and ensuring complete recording and reporting which could be enhanced by quarterly cohort review. Older aged and rural patients need special attention. Furthermore, the sample referral network should be strengthened.
An exploratory pilot study evaluating the supplementation of standard antibiotic therapy with probiotic lactobacilli in south African women with bacterial vaginosis
Authors: Marcotte Harold , Larsson Per Göran , Andersen Kasper Krogh , Zuo Fanglei , Mikkelsen Lasse Sommer , Brandsborg Erik , Gray Glenda , Laher Fatima , Otwombe Kennedy 
Published: September 2019

Abstract

Background
To reduce acquisition and relapse of bacterial vaginosis (BV), lactobacilli must be maintained in the vaginal microbiome. Probiotic lactobacilli may aid this purpose. We investigated whether vaginal probiotics (containing Lactobacillus rhamnosus DSM 14870 and Lactobacillus gasseri DSM 14869) would result in vaginal colonisation with lactobacilli in women with and without BV.

Methods
This prospective, partially randomised, exploratory pilot study was conducted in Soweto, South Africa. Thirty-nine sexually-active, HIV negative women were enrolled from October 2014 to May 2016 into three arms. Women who did not have BV (Group 1, n = 13) self-administered probiotic capsules vaginally once daily for 30 days, then once a week until Day 190. Women diagnosed with BV were randomized into Group 2 (n = 12) or Group 3 (n = 14) and treated with the triple oral antibiotic combination for vaginal discharge syndrome per South African guidelines (cefixime 400 mg stat, doxycycline 100 mg BD for 7 days and metronidazole 2 g stat). Immediately after antibiotic treatment, women in Group 2 self-administered probiotic capsules vaginally once daily for 30 days then vaginally once a week until Day 190. Women in Group 3 were not given lactobacilli.

Results
During the study, L. rhamnosus DSM 14870 or L. gasseri DSM 14869, were isolated in 5/13 (38.5%) women in Group 1 compared to 10/12 (83.3%) women in Group 2 (p = 0.041). The 1-month and 6-month BV cure rates were similar (P >  0.05) between Group 2 (42 and 25%) compared to Group 3 (36 and 25%). In Group 2, no correlation was observed between the frequency of isolation of the two Lactobacillus strains and the 1-month or 6-month cure rate.

Conclusions
Supplementation with vaginal probiotic capsules resulted in colonisation of the vagina by the Lactobacillus strains (L. rhamnosus DSM 14870 and L. gasseri DSM 14869) contained in the capsules. We observed low initial cure rates of BV after a stat dose of metronidazole and that the probiotic did not improve BV cure rates or alleviate recurrence which could be due to treatment failure or very limited power of the study.

Trial registration
Registered at the Pan African Clinical Trial Registry (www.pactr.org) on April 13, 2018 (retrospectively registered). Trial identification number: PACTR201804003327269.
Incidence and predictors of lost to follow-up among drug-resistant tuberculosis patients at University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia: a retrospective follow-up study
Authors: Kassa Getahun Molla , Teferra Alemayehu Shimeka , Wolde Haileab Fekadu , Muluneh Atalay Goshu , Merid Mehari Woldemariam 
Published: September 2019

Abstract

Background
The emergence of Drug-Resistance Tuberculosis (DR-TB) is an increasing global public health problem. Lost to Follow-up (LTFU) from DR-TB treatment remains a major barrier to tuberculosis epidemic control and better treatment outcome. In Ethiopia, evidences on the incidence and predictors of LTFU are scarce. Thus, this study aimed to determine the incidence and identify the predictors of LTFU among DR-TB patients.

Methods
A retrospective follow-up study was conducted among a total of 332 DR-TB patients at the University of Gondar comprehensive specialized hospital. Data were retrieved from patient records from September 2010 to December 2017 and entered in to Epi-data 4.2.0.0 and analysed using Stata14.1 software. The risk was estimated using the Nelson-Aalen cumulative hazard curve. A log-rank test was used for survival comparisons between categories of independent variables. The Gompertz regression model was fitted, and hazard ratio with a 95% confidence interval (CI) was used to measure the strength of associations. Variables with less than 0.05 p-values in the multivariable model were considered as significantly associated with LTFU.

Results
Among a total of 332 patient records reviewed, 206 (62.05%) were male. The median age was 30 years (Inter Quartile Range (IQR): 23–40). Forty-one (12.35%) of the participants had no history of TB treatment, while a quarter of were TB-HIV co-infected. Closely all (92.17%) of the patients had pulmonary tuberculosis. The median follow up time was 20.37 months (IQR: 11.02, 21.80). Thirty-six (10.84%) patients were lost from follow-up with an incidence rate of 6.47 (95% CI: 4.67, 8.97)/1000 Person Months (PM). Homelessness (Adjusted Hazard Ratio (AHR) =2.51, 95%CI: 1.15, 5.45) and treatment enrolment year from 2013 to 2014 (AHR = 3.25, 95% CI: 1.30, 8.13) were significant predictors of LTFU.

Conclusion
This study indicated that LTFU among DR-TB registered patients was high in the first six months compared to subsequent months. Homelessness and year of treatment enrolment were independent predictors of LTFU, requiring more economic support to patients in order to ensure treatment completion. This result can be generalized to patients who are using DR-TB treatment in similar settings.
Maternal complications in twin pregnancies in Finland during 1987–2014: a retrospective study
Authors: Rissanen Annu-Riikka S. , Jernman Riina M. , Gissler Mika , Nupponen Irmeli , Nuutila Mika E. 
Published: September 2019

Abstract

Background
To investigate the trends and changes in the incidence and overall outcome of twin pregnancies in Finland, a retrospective study was conducted with emphasis on maternal complications, covering a 28-year study period.

Methods
All 23,498 twin pregnancies with 46,363 live born and 633 stillborn children in Finland during 1987–2014 were included in the study. Data were collected from the national Medical Birth Register and the Care Register on Hospital Care (Finnish Institute for Health and Welfare, Finland) regarding the parturients’ characteristics and incidences of several pregnancy and childbirth complications. The incidences of twin pregnancies and maternal complications during pregnancy and childbirth are the main outcome measures of the study. The results are expressed in percentages, means, medians, ranges and standard deviations (SD), when appropriate.

Results
Twins comprised 1.4% of all births in Finland in 1987–2014. Parturients’ mean age has remained stable, but the share of over 35 year-old parturients is increasing. The incidences of pre-eclampsia, intrahepatic cholestasis of pregnancy, gestational diabetes and postpartum haemorrhage have risen during the study period. Almost half (44.9%) of twins were born preterm, almost half via Caesarean section (47.1%), and 27.7% of twin labours were induced.

Conclusions
Several pregnancy complications increased during the study period. Advanced maternal age among twin parturients has risen, enhancing the risks for developing complications in a pregnancy already of a high-risk category, and predisposing to preterm delivery. National and international guidelines are necessary to improve the overall outcome of twin pregnancies.
Circ-Foxo3 is positively associated with the Foxo3 gene and leads to better prognosis of acute myeloid leukemia patients
Authors: Zhou Jiao , Zhou Ling-Yu , Tang Xi , Zhang Jing , Zhai Ling-Ling , Yi Yun Yun , Yi Jing , Lin Jiang , Qian Jun , Deng Zhao-Qun 
Published: September 2019

Abstract

Background
The Foxo3 gene, belonging to the forkhead family, is one of the classes of transcription factors characterized by a forkhead DNA-binding domain, which usually considered being a cancer suppressor gene. Circ-Foxo3 is a circular structure which connects the 3’end to the 5’end. Scholars detected that circ-Foxo3 could compete with Foxo3 for binding to some miRNAs.

Methods
In this study, we will test the expression of Foxo3 and circ-Foxo3 in de novo acute myeloid leukemia (AML) patients to explore the relationship between Foxo3 gene and circ-Foxo3. All the de novo AML samples and normal control samples was measured by real-time quantitative PCR. A receiver operating characteristic curve was conducted to differentiate AML patients from control people. Association of Foxo3 expression and overall survival was conducted by Kaplan-Meier survival analysis.

Results
We found that the expression of Foxo3 gene in de novo patients was significantly lower than control samples (P = 0.009). Meanwhile, circ-Foxo3 also expressed lower in de novo AML patients than in control samples (P = 0.040). In different classifications, this trend could be observed more remarkably. In non-M3 patients, the Foxo3 high patients’ survival time was longer than Foxo3 low patients (P = 0.002). Besides, in non-favorable risk groups, patients with low expression of Foxo3 had longer survival time than Foxo3 high patients (P = 0.004). Furthermore, in normal Karyotypic patients, the overall survival time of patients with high-expressed Foxo3 was significantly longer than those with low expression (P = 0.034). Besides, Pearson analysis was also conducted between these two genes in AML patients. Results revealed that they were positively correlated (R = 0.63, P < 0.001).

Conclusion
In conclusion, we found that low expression of circ-Foxo3 and Foxo3 were frequent in AML patients, and patients with high expression of Foxo3 often had a trend of better prognosis.
Mapping patterns of metastatic lymph nodes for postoperative radiotherapy in thoracic esophageal squamous cell carcinoma: a recommendation for clinical target volume definition
Authors: Yu Jing , Ouyang Wen , Li Chunyang , Shen Jiuling , Xu Yu , Zhang Junhong , Xie Conghua 
Published: September 2019

Abstract

Background
The clinical target volume (CTV) for postoperative radiotherapy for thoracic esophageal squamous cell carcinoma (TESCC) needs to be defined. The study aim was to map metastatic lymph nodes (LNMs) in a computed tomography (CT)-based atlas and delineate the postoperative radiotherapy target area.

Methods
Sixty-nine TESCC patients with first recurrent regional LNMs after esophagectomy were included. The LNM epicenters were registered onto corresponding anatomic axial CT images of a standard patient in the treatment position, with reference to the surrounding vascular and bony structures. The LNM sites were based on lymph node map of esophageal cancer, AJCC 8th. The lymph metastasis risk for different segments of thoracic esophagus was assessed.

Results
One hundred and seventy-nine LNMs were mapped onto standard axial CT images. The upper-middle mediastinum region (station 1 to 8 M) contained 97% of metastases in the upper segment of thoracic esophagus, 90% in the middle segment, and 66% in the lower one. Advanced pathological stage (≥IIIB) might be a predictive factor for upper abdominal region (UAR) relapse in lower TESCC. Lower cervical para-tracheal LNMs were within a 4.3-cm bilaterally expanded area from the midline of the body and a 2.2-cm expanded area from the anterior of vertebral body, from the superior border of the C7, to the inferior border of the first thoracic vertebra.

Conclusion
A modified target from the upper border of C7 to the lower border of caudal margin of the inferior pulmonary vein level could cover the high-risk area of TESCC underwent postoperative radiotherapy. UAR seems to be an elective irradiation target for lower TESCC at pathological IIIB stage and higher.