bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis
Authors: Motte Jeremias , Fisse Anna Lena , Grüter Thomas , Schneider Ruth , Breuer Thomas , Lücke Thomas , Krueger Stefan , Nguyen Huu Phuc , Gold Ralf , Ayzenberg Ilya , Ellrichmann Gisa 
Published: December 2019

Abstract
Background
Hyperprolinemia type 2 (HPII) is a rare autosomal recessive disorder of the proline metabolism, that affects the ALDH4A1 gene. So far only four different pathogenic mutations are known. The manifestation is mostly in neonatal age, in early infancy or early childhood.

Case presentation
The 64-years female patient had a long history of abdominal pain, and episode of an acute neuritis. Ten years later she was admitted into the neurological intensive-care-unit with acute abdominal pain, multiple generalized epileptic seizures, a vertical gaze palsy accompanied by extensive lactic acidosis in serum 26.0 mmol/l (reference: 0.55–2.2 mmol/l) and CSF 12.01 mmol/l (reference: 1.12–2.47 mmol/l). Due to repeated epileptic seizures and secondary complications a long-term sedation with a ventilation therapy over 20 days was administered. A diagnostic work-up revealed up to 400-times increased prolin-level in urine CSF and blood. Furthermore, a low vitamin-B6 serum value was found, consistent with a HPII causing secondary pyridoxine deficiency and seizures. The ALDH4A1 gene sequencing confirmed two previously unknown compound heterozygous variants (ALDH4A1 gene (NM_003748.3) Intron 1: c.62 + 1G > A - heterozygous and ALDH4A1 gene (NM_003748.3) Exon 5 c.349G > C, p.(Asp117His) - heterozygous). Under high-dose vitamin-B6 therapy no further seizures occurred.

Conclusion
We describe two novel ALDH4A1-variants in an adult patient with hyperprolinemia type II causing secondary pyridoxine deficiency and seizures. Severe and potentially life-threatening course of this treatable disease emphasizes the importance of diagnostic vigilance and thorough laboratory work-up including gene analysis even in cases with atypical late manifestation.
Loss of Stag2 cooperates with EWS-FLI1 to transform murine Mesenchymal stem cells
Authors: El Beaino Marc , Liu Jiayong , Wasylishen Amanda R. , Pourebrahim Rasoul , Migut Agata , Bessellieu Bryan J. , Huang Ke , Lin Patrick P. 
Published: January 2020

Abstract
Background
Ewing sarcoma is a malignancy of primitive cells, possibly of mesenchymal origin. It is probable that genetic perturbations other than EWS-FLI1 cooperate with it to produce the tumor. Sequencing studies identified STAG2 mutations in approximately 15% of cases in humans. In the present study, we hypothesize that loss of Stag2 cooperates with EWS-FLI1 in generating sarcomas derived from murine mesenchymal stem cells (MSCs).

Methods
Mice bearing an inducible EWS-FLI1 transgene were crossed to p53−/− mice in pure C57/Bl6 background. MSCs were derived from the bone marrow of the mice. EWS-FLI1 induction and Stag2 knockdown were achieved in vitro by adenovirus-Cre and shRNA-bearing pGIPZ lentiviral infection, respectively. The cells were then treated with ionizing radiation to 10 Gy. Anchorage independent growth in vitro was assessed by soft agar assays. Cellular migration and invasion were evaluated by transwell assays. Cells were injected with Matrigel intramuscularly into C57/Bl6 mice to test for tumor formation.

Results
Primary murine MSCs with the genotype EWS-FLI1 p53−/− were resistant to transformation and did not form tumors in syngeneic mice without irradiation. Stag2 inhibition increased the efficiency and speed of sarcoma formation significantly in irradiated EWS-FLI1 p53−/− MSCs. The efficiency of tumor formation was 91% for cells in mice injected with Stag2-repressed cells and 22% for mice receiving cells without Stag2 inhibition (p < .001). Stag2 knockdown reduced survival of mice in Kaplan-Meier analysis (p < .001). It also increased MSC migration and invasion in vitro but did not affect proliferation rate or aneuploidy.

Conclusion
Loss of Stag2 has a synergistic effect with EWS-FLI1 in the production of sarcomas from murine MSCs, but the mechanism may not relate to increased proliferation or chromosomal instability. Primary murine MSCs are resistant to transformation, and the combination of p53 null mutation, EWS-FLI1, and Stag2 inhibition does not confer immediate conversion of MSCs to sarcomas. Irradiation is necessary in this model, suggesting that perturbations of other genes beside Stag2 and p53 are likely to be essential in the development of EWS-FLI1-driven sarcomas from MSCs.
Correction to: Human papillomavirus type 18 oncoproteins exert their oncogenicity in esophageal and tongue squamous cell carcinoma cell lines distinctly
Authors: Boon Siaw Shi , Chen Zigui , Li Jintao , Lee Karen Y. C. , Cai Liuyang , Zhong Rugang , Chan Paul K. S. 
Published: December 2019

Following publication of the original article [1], the authors reported that during the production process, Table 1 was omitted.
Comparison between refractive outcomes of femtosecond laser-assisted cataract surgery and standard phacoemulsification
Authors: Shaheen Mohamed Shafik , AbouSamra Amir , Helaly Hany Ahmed , Said Amr , Elmassry Ahmed 
Published: January 2020

Abstract
Background
To compare the visual and refractive outcomes of femtosecond laser assisted cataract surgery (FLACS) using Victus platform (Technolas Bausch and Lomb (B&L), Munich, Germany) and conventional phacoemulsification cataract surgery (CPCS).

Methods
A retrospective study of 100 eyes operated for cataract. FLACS was performed in 50 eyes and CPCS was done in another 50 eyes. Preoperative and 6 months postoperative visual and refractive evaluation (efficacy, safety, predictability, and surgically induced astigmatism) as well as higher-order aberrations were analyzed. Efficacy index which equals post-operative mean of uncorrected distance visual acuity (UDVA) divided by preoperative mean corrected distance visual acuity (CDVA) was calculated in both groups. Safety index equals post-operative mean of corrected distance visual acuity (CDVA) divided by preoperative mean CDVA.

Results
Logarithm of the Minimum Angle of Resolution (LogMAR), UDVA improved in both groups after surgery (p < 0.05). It was 0.23 ± 0.20 and 0.291 ± 0.311 log MAR in FLACS and CPCS groups respectively. Safety index was 1.777 in FLACS group and 1.744 in CPCS groups showing high degree of safety of both measures. Mean surgically induced astigmatism (SIA) was 0.35 ± 0.67 D and 0.901 ± 0.882 D in FLACS and CPCS groups respectively (p = 0.015). The post-operative comparison between both groups was in favor of CPCS group vs. FLACS group regarding total aberrations (0.563 ± 0.386 vs. 0.91 ± 1.20) (p = 0.03), while low order aberrations were significantly less in FLACS group vs. CPCS group (0.64 + 0.63 vs. 2.07 + 3.15) (p = 0.027). RMS high order aberration was higher in FLACS group vs. CPCS group but of no statistical significance 0.54 ± 0.96 vs. 0.328 ± 0.360 (p = 0.082).

Conclusion
Femtosecond laser -assisted cataract surgery was a safe and precise procedure but enhanced visual outcomes only minimally when compared to conventional cataract surgery in experienced hands. Both FLACS and manual surgeries can achieve a high efficacy, predictability and safety with slight superior outcomes in FLACS.

Trial registration number
PACTR201804003256258 (date: 27 Mar 2018) Available at: https://pactr.samrc.ac.za/
Risk factors associated with osteonecrosis of femoral head after internal fixation of femoral neck fracture:a systematic review and meta-analysis
Authors: Xu Jing-Li , Liang Zheng-Rong , Xiong Bing-Lang , Zou Qi-Zhao , Lin Tian-Ye , Yang Peng , Chen Da , Zhang Qing-Wen 
Published: December 2019

Abstract
Background
Although the risk factors associated with osteonecrosis of femoral head (ONFH) after internal fixation of femoral neck fracture (IFFNF) have been frequently reported, the results remain controversial. Therefore, its related risk factors were systematically evaluated and meta-classified in this study.

Methods
Literature on risk factors of ONFH caused by IFFNF was retrieved in PubMed, Embase and Cochrane Library due June 2019. Review Manager 5.3 software was applied to data synthesis, and Stata 13.0 software was adopted for analyses of publication bias and sensitivity.

Results
A total of 17 case-control studies with 2065 patients were included. The risk of ONFH after IF was 0.40-fold higher in patients with Garden III-IV FNF than that in patients with Garden I-II (OR: 0.40, 95%CI: 0.29–0.55). The risk of OFNH with retained IF was uplifted by 0.04 times (OR: 0.04, 95%CI: 0.02–0.07). There was nonsignificant relationship between gender and ONFH after IFFNF (OR: 1.27, 95%CI: 0.84–1.94). Moreover, ONFH after IFFNF presented no association with age (OR:1.66, 95%CI: 0.89–3.11), injury-operation interval (OR:1.29, 95%CI: 0.82–2.04), fracture reduction mode (OR:1.98, 95%CI: 0.92–4.26), preoperative traction (OR:1.69, 95%CI: 0.29–9.98) and mechanism of injury (OR:0.53, 95%CI: 0.06–4.83). Egger’s and Begg’s tests indicated a publication bias (P = 0.001).

Conclusion
It was demonstrated that Garden classification and retained IF were important influencing factors of ONFH after IFFNF. Gender, age, injury-operation interval, fracture reduction mode, preoperative traction and the mechanism of ONFH were irrelevant to the complication.
Diagnostic potential of ultrasound in carpal tunnel syndrome with different etiologies: correlation of sonographic median nerve measures with electrodiagnostic severity
Authors: Elnady Basant , Rageh Elsayed M. , Ekhouly Tohamy , Fathy Sabry M. , Alshaar Mohamed , Fouda El Saeed , Attar Mohammed , Abdelaal Ahmed M. , El Tantawi Ahmed , Algethami Mohammed M. , Bong David 
Published: December 2019

Abstract
Background
Carpal tunnel syndrome (CTS) is the commonest entrapment neuropathy. The aim of this study was to assess the accuracy and validity of high resolution musculoskeletal ultrasound (US) in the diagnosis of CTS in the Saudi population.

Methods
Sixty patients were diagnosed clinically to have CTS involving 89 wrists that were confirmed by neurophysiologic studies. Each affected wrist was characterized as idiopathic or associated with either diabetes mellitus or hypothyroidism and were assigned a severity grade based on results of neurophysiologic studies. Seventy-six healthy wrists from fifty age, sex and BMI matched healthy subjects were included in the control group. High resolution ultrasound (US) was performed to assess median nerve cross sectional area distal (CSAd) at the entry to the carpal tunnel and proximally (CSAp) at the level of pronator quadratus muscle with a further calculation of their difference (ΔCSA) and their mean average or CSAd+CSAp/2 (CSApd).

Results
There was a significant difference between both groups regarding mean ± SD of CSAd, CSAp, ∆CSA, and CSApd (p = 0.0001). A positive significant correlation was also found between the CSAd, ∆ CSA and the CSApd measurements with neurophysiologic severity grade of CTS (P = 0.001). A ∆CSA threshold of 2.5 mm2 showed the highest sensitivity and specificity to diagnose CTS in Saudis.

Conclusion
High resolution ultrasound is a valid and accurate diagnostic modality in carpal tunnel syndrome and correlated to CTS severity. A ∆CSA greater than 2.5 mm2 is considered a valid diagnostic value for CTS in our Saudi population. CTS in our patients with diabetes tend to have greater median nerve US measurement values.
Navigation-assisted suture anchor insertion for arthroscopic rotator cuff repair
Authors: Micic Ivan , Kholinne Erica , Hong Hanpyo , Choi Hyunseok , Kwak Jae-Man , Sun Yucheng , Hong Jaesung , Koh Kyoung-Hwan , Jeon In-Ho 
Published: December 2019

Abstract
Background
Suture anchor placement for subscapularis repair is challenging. Determining the exact location and optimum angle relative to the subscapularis tendon direction is difficult because of the mismatch between a distorted arthroscopic view and the actual anatomy of the footprint. This study aimed to compare the reliability and reproducibility of the navigation-assisted anchoring technique with conventional arthroscopic anchor fixation.

Methods
Arthroscopic shoulder models were tested by five surgeons. The conventional and navigation-assisted methods of suture anchoring in the subscapularis footprint on the humeral head were tested by each surgeon seven times. Angular results and anchor locations were measured and compared using the Wilcoxon signed rank test. Interobserver intraclass correlation coefficients (ICCs) were analyzed among the surgeons.

Results
The mean angular errors of the targeted anchor fixation guide without and with navigation were 17° and 2° (p < 0.05), respectively, and the translational errors were 15 and 3 mm (p < 0.05), respectively. All participants showed a narrow range of anchor fixation angular and translational errors from the original target. Among the surgeons, the interobserver reliabilities of angular errors for ICCs of the navigation-assisted and conventional methods were 0.897 and 0.586, respectively, and the interobserver ICC reliabilities for translational error were 0.938 and 0.619, respectively.

Conclusions
The navigation system may help surgeons be more aware of the surrounding anatomy and location, providing better guidance for anchor orientation, including footprint location and anchor angle.
Study protocol of coaching end-of-life palliative care for advanced heart failure patients and their family caregivers in rural appalachia: a randomized controlled trial
Authors: Piamjariyakul Ubolrat , Petitte Trisha , Smothers Angel , Wen Sijin , Morrissey Elizabeth , Young Stephanie , Sokos George , Moss Alvin H. , Smith Carol E. 
Published: December 2019

Abstract
Background
Heart failure (HF) afflicts 6.5 million Americans with devastating consequences to patients and their family caregivers. Families are rarely prepared for worsening HF and are not informed about end-of-life and palliative care (EOLPC) conservative comfort options especially during the end stage. West Virginia (WV) has the highest rate of HF deaths in the U.S. where 14% of the population over 65 years have HF. Thus, there is a need to investigate a new family EOLPC intervention (FamPALcare), where nurses coach family-managed advanced HF care at home.

Methods
This study uses a randomized controlled trial (RCT) design stratified by gender to determine any differences in the FamPALcare HF patients and their family caregiver outcomes versus standard care group outcomes (N = 72). Aim 1 is to test the FamPALcare nursing care intervention with patients and family members managing home supportive EOLPC for advanced HF. Aim 2 is to assess implementation of the FamPALcare intervention and research procedures for subsequent clinical trials. Intervention group will receive routine standard care, plus 5-weekly FamPALcare intervention delivered by community-based nurses. The intervention sessions involve coaching patients and family caregivers in advanced HF home care and supporting EOLPC discussions based on patients’ preferences. Data are collected at baseline, 3, and 6 months. Recruitment is from sites affiliated with a large regional hospital in WV and community centers across the state.

Discussion
The outcomes of this clinical trial will result in new knowledge on coaching techniques for EOLPC and approaches to palliative and end-of-life rural home care. The HF population in WV will benefit from a reduction in suffering from the most common advanced HF symptoms, selecting their preferred EOLPC care options, determining their advance directives, and increasing skills and resources for advanced HF home care. The study will provide a long-term collaboration with rural community leaders, and collection of data on the implementation and research procedures for a subsequent large multi-site clinical trial of the FamPALcare intervention. Multidisciplinary students have opportunity to engage in the research process.

Trial registration
ClinicalTrials.gov NCT04153890, Registered on 4 November 2019
A qualitative study on reasons for early removal of Implanon among users in Arba Minch town, Gamo Goffa zone, South Ethiopia: a phenomenological approach
Authors: Utaile Mesfin Mamo , Debere Mesfin Kote , Nida Etsehiwot Tilahun , Boneya Dube Jara , Ergano Amsale Tekle 
Published: January 2020

Abstract
Background
Implanon is one of the cost - effective long acting reversible contraceptive methods used for spacing and limiting births in Ethiopia. Despite the scaling up initiative undertaken by the Ethiopian Government, Implanon uptake is very low compared to short acting contraceptive methods. There is low utilization of Implanon with high level of discontinuation in Ethiopia. Therefore, this study was conducted to explore the reasons for early removal of Implanon among users in Arba Minch town, South Ethiopia.

Methods
A community-based qualitative exploratory study using phenomenological approach was conducted. In-depth and key informant interviews were used to collect data from April 20–27, 2018 in Arba Minch town. Convenient sampling was employed to recruit participants from the households of targeted villages. A total of 10 in-depth interviews with women who recently removed Implanon and 5 key informant interviews with health extension workers were conducted. The sample size was determined based on the concept of saturation. The collected data were analyzed using thematic content analysis technique. Data coding and analysis were facilitated by using Open code version 4.0 software.

Results
This study revealed that majority of participants were able to mention at least three types of contraceptive methods available in the nearby health facilities. The study underlined that side effect of the method, husband opposition, seeking more children, and method failure were the common reasons for early removal of Implanon, in which side effect of the method was the main reason. Among various forms of side effects of Implanon identified by users, heavy and irregular bleeding was mentioned as the most frequently occurring side effect.

Conclusion
Our result indicated that heavy and irregular bleeding was the main reason for early removal of Implanon. Therefore it suggests improvement in the service delivery system. Improving client’s education and counseling service program could contribute much to avoid unreasonable and untimely removal of Implanon.
Drug prescription goals in primary care: a cross-sectional study
Authors: Bernard Louis , Ecochard René , Gueyffier François , Letrilliart Laurent 
Published: January 2020

AbstractBackgroundCare goals are often implicit, although their identification is a key element of any prescription process. This study aimed to describe the clinical goals of drug prescriptions in general practice, their determinants and the agreement between physicians and patients.MethodsThis was a cross-sectional study conducted by 11 resident trainees acting as observers in 23 general practices. The residents recorded the indication and main physician’s goal for all drugs prescribed during five consultation days in each practice in December 2015, and the main patient’s goal for a sub-sample of consultations. We used an eight-category generic classification of prescription goals, including three specific (mortality, morbidity and cure), three non-specific (symptoms, quality of life, functioning) and two non-specified (other goal, no goal) categories. Analyses were based on a multivariable, multilevel model and on the kappa statistic applied to the sub-sample of consultations.ResultsThe sample encompassed 2141 consultations and 5036 drugs. The main physicians’ goal of drug prescriptions was to relieve symptoms (43.3%). The other goals were to decrease the risk of morbidity (22.4%), to cure disease (11.7%), to improve quality of life (10.6%), to decrease the risk of mortality (8.5%) and to improve functioning (1.8%). The choice of a specific goal was more frequent in patients with the following characteristics: over 50 (OR [1.09;1.15]), of male gender (OR [1.09;1.39]), with full financial coverage for a long-term condition (OR [1.47;1.97]), known by the physician (OR [1.19;2.23]), or with a somatic health problem (OR [2.56;4.17]). Cohen’s kappa for drug prescription goals between the patients and the physicians was 0.26 (0.23–0.30).ConclusionsPhysicians’ goals are poorly shared with patients. It remains to be assessed whether it is possible to collect and discuss information on prescription goals on a daily basis.
Functional architecture underlying binocular coordination of eye position and velocity in the larval zebrafish hindbrain
Authors: Brysch Christian , Leyden Claire , Arrenberg Aristides B. 
Published: December 2019

AbstractBackgroundThe oculomotor integrator (OI) in the vertebrate hindbrain transforms eye velocity input into persistent position coding output, which plays a crucial role in retinal image stability. For a mechanistic understanding of the integrator function and eye position control, knowledge about the tuning of the OI and other oculomotor nuclei is needed. Zebrafish are increasingly used to study integrator function and sensorimotor circuits, yet the precise neuronal tuning to motor variables remains uncharacterized.ResultsHere, we recorded cellular calcium signals while evoking monocular and binocular optokinetic eye movements at different slow-phase eye velocities. Our analysis reveals the anatomical distributions of motoneurons and internuclear neurons in the nucleus abducens as well as those of oculomotor neurons in caudally adjacent hindbrain volumes. Each neuron is tuned to eye position and/or velocity to variable extents and is only activated after surpassing particular eye position and velocity thresholds. While the abducens (rhombomeres 5/6) mainly codes for eye position, in rhombomeres 7/8, a velocity-to-position coding gradient exists along the rostro-caudal axis, which likely corresponds to the oculomotor structures storing velocity and position, and is in agreement with a feedforward mechanism of persistent activity generation. Position encoding neurons are recruited at eye position thresholds distributed across the behaviourally relevant dynamic range, while velocity-encoding neurons have more centred firing thresholds for velocity. In the abducens, neurons coding exclusively for one eye intermingle with neurons coding for both eyes. Many of these binocular neurons are preferentially active during conjugate eye movements and less active during monocular eye movements. This differential recruitment during monocular versus conjugate tasks represents a functional diversification in the final common motor pathway.ConclusionsWe localized and functionally characterized the repertoire of oculomotor neurons in the zebrafish hindbrain. Our findings provide evidence for a mixed but task-specific binocular code and suggest that generation of persistent activity is organized along the rostro-caudal axis in the hindbrain.