bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Surgery for Contouring the Prominent Zygoma and Mandibular Angles With Facelift in Middle-Aged Patients
Authors: Zhou Jing , Qi Zuoliang , Jin Xiaolei
Published: January 2020

Background:

As the pursuit of higher self-attractiveness grows, an increasing number of middle-aged people are unsatisfied with their facial contour and required osteotomy. However, for these patients, performing osteotomy only would accelerate the aging process. Herein, the authors put forward simultaneous surgery for contouring the prominent zygoma and mandible with facelift for elderly patients.

Methods:

Patients were divided into 3 groups: group A with prominent mandible, group B with protruding zygoma, and group C with prominent mandible and zygoma. By implementing intraoral incision, outer cortex grinding, mandibular angle curved osteotomy, and reduction malarplasty were performed. Through facelift incision, the zygomatic arch was reduced and facelift was conducted. Patients were followed up for at least 12 months and were asked to evaluate their experience.

Results:

From March 2009 to January 2018, a total of 55 patients received the surgery: 17 patients received mandibular angle osteotomy and facelift, 22 received malarplasty and facelift, and 16 underwent mandible and zygoma contouring and facelift. The recovery process was uneventful, with only 2 patients in group A and 1 patient in group C who suffered from a hematoma, which relieved without surgical intervene. The postoperative images showed smoother facial contours. Patients were satisfied with surgical outcomes. Significant improvements were seen comparing pre- and postoperative photos.

Conclusion:

Conducting osteotomy and rhytidectomy concurrently results in smooth facial contour and youthful appearance which improves patients’ self-image and contributes to high patients’ satisfaction. With a low complication rate and no long-term complication, the surgery is safe to perform.

Level of Evidence:

Level IV, the case study.
Large-Volume Vascularized Muscle Grafts Engineered From Groin Adipose Tissue in Perfusion Bioreactor Culture
Authors: An Yang , Reimers Kerstin , Allmeling Christina , Liu Jieli , Lazaridis Andrea , Strauss Sarah , Vogt Peter M.
Published: January 2020

Background:

Muscle tissue engineering still remains a major challenge. An axial vascular pedicle and a perfusion bioreactor are necessary for the development and maintenance of a large-volume engineered muscle tissue to provide circulation within the construct. This study aimed to determine whether large-volume vascularized muscle-like constructs could be made from rat groin adipose tissue in a perfusion bioreactor.

Methods:

Epigastric adipofascial flaps based on the inferior superficial epigastric vessels were elevated bilaterally in male Lewis rats and connected to the bioreactor. The system was run using a cable pump and filled with myogenic differentiation medium in the perfusion bioreactor for 1, 3, 5, or 7 weeks. The resulting tissue constructs were characterized with respect to the morphology and muscle-related expression of genes and proteins.

Results:

The histological examination demonstrated intact muscle-like tissue fibers; myogenesis was verified by the expression of myosin, MADS box transcription enhancer factor 2 D, desmin—a disintegrin and metalloproteinase domain (ADAM) 12—and M-cadherin using reverse transcription–polymerase chain reaction. Western blot analysis for desmin, MyoD1, N-cadherin, and ADAM12 was performed to verify the myogenic phenotype of the extracted differentiated tissue and prove the formation of muscle-like constructs.

Conclusions:

A large-volume vascularized muscle tissue could be engineered in a perfusion bioreactor. The resulting tissue had muscle-like histological features and expressed muscle-related genes and proteins, indicating that the trans-differentiation of adipose tissue into muscle tissue occurred.
Proenkephalin Compared to Conventional Methods to Assess Kidney Function in Critically Ill Sepsis Patients
Authors: Beunders Remi , van Groenendael Roger , Leijte Guus P. , Kox Matthijs , Pickkers Peter
Published: January 2020

Background:

The assessment of renal function in clinical practice remains challenging. Using creatinine to assess the glomerular filtration rate (GFR) is notoriously inaccurate, and determination of the true GFR, e.g., using inulin or iohexol, is laborious and not feasible in daily practice. Proenkephalin (PENK) is a novel candidate biomarker for kidney function that is filtrated in the glomerulus, has shown to represent steady-state GFR in patients with different severities of renal insufficiency. In this pilot study in non-steady-state critically ill patients, we compared plasma PENK concentrations with creatinine-based GFR assessments and validated both against the “true GFR” measured using a gold standard method: iohexol plasma clearance.

Methods:

Twenty-three critically ill patients with septic shock were included. Kidney function was determined using the Modification of Diet in Renal Disease formula (eGFRMDRD), Endogenous Creatinine Clearance (GFRECC), and iohexol plasma clearance (GFRiohexol) during a 6-h window. Plasma PENK concentrations were measured using the penKid immunoassay.

Results:

The eGFRMDRD and GFRECC correlated with the GFRiohexol (R

2
 = 0.82, P < 0.0001 and R

2
 = 0.82, P < 0.0001 respectively); however, bias and variability were considerable: the eGFRMDRD overestimated the true GFR with 31 ± 35% (95% limits of agreement: −37% to 100%) and the GFRECC with 37 ± 49% (95% limits of agreement: −59% to 133%). Plasma PENK concentrations showed a very strong inverse correlation with the GFRiohexol (R

2
 = 0.90, P < 0.0001) which tended to be better compared with the correlation of eGFRMDRD (P = 0.06) and GFRECC (P = 0.08) with the GFRiohexol.

Conclusions:

In this pilot study in non-steady-state critically ill sepsis patients, GFR appears to be more accurately reflected by plasma PENK concentrations compared to conventional creatinine-based methods. Therefore, PENK holds promise as an accurate and feasible biomarker to determine kidney function during non-steady-state conditions in the critically ill.
A Randomized Controlled Trial of Endovenous Laser Ablation Versus Mechanochemical Ablation With ClariVein in the Management of Superficial Venous Incompetence (LAMA Trial)
Authors: Mohamed Abduraheem Hussein , Leung Clement , Wallace Tom , Smith George , Carradice Daniel , Chetter Ian
Published: January 2020

Objective:

This RCT compares the clinical, technical and quality of life outcomes after EVLA and MOCA.

Summary of Background Data:

Thermal ablation is the current mainstay treatment for SVI. Newer nonthermal methods of treatment have been developed which do not require the use of tumescent anesthesia. The potential advantages of these newer methods should be tested in RCTs to ascertain their role in the future treatments of SVI.

Methods:

This single-center RCT enrolled patients with symptomatic, unilateral, single-axis SVI. Eligible patients were equally randomized to either EVLA or MOCA, both with concomitant phlebectomy when necessary. The joint primary outcomes were intraprocedural axial ablation pain scores and anatomical occlusion at 1 year. Secondary outcomes included postprocedural pain, venous clinical severity score (VCSS), quality of life (Aberdeen varicose veins questionnaire and EuroQol 5-domain utility index), patient satisfaction and complication rates.

Results:

One hundred fifty patients were randomized equally between the 2 interventions. Both groups reported low intraprocedural pain scores; on a 100 mm visual analog scale, pain during axial EVLA was 22 (9–44) compared to 15 (9–29) during MOCA; P = 0.210. At 1 year, duplex derived anatomical occlusion rates after EVLA were 63/69 (91%) compared to 53/69 (77%) in the MOCA group; P = 0.020. Both groups experienced significant improvement in VCSS and AVVQ after treatment, without a significant difference between groups. Median VCSS improved from 6 (5–8) to 0 (0–1) at one year; P < 0.001. Median AVVQ improved from 13.8 (10.0–17.7) to 2.0 (0.0–4.9); P < 0.001. One patient in the MOCA group experienced DVT.

Conclusions:

Both EVLA and MOCA were highly efficacious in treating SVI; patients improved significantly in terms of disease severity, symptoms, and QoL. Both resulted in low procedural pain with a short recovery time. Axial occlusion rates were higher after EVLA. Long term follow-up is warranted to assess the effect of recanalization on the rate of clinical recurrence.
Preoperative Progressive Pneumoperitoneum Enables Defect Closure and Laparoscopic Repair of Large Parastomal Hernias
Authors: Tang Fuxin , Ma Ning , Li Ying-Ru , Gan Wen-Chang , Zong Zhen , Zhou Tai-Cheng , Chen Shuang
Published: January 2020

Purpose:

Preoperative progressive pneumoperitoneum (PPP) has not been reported in the management of parastomal hernias; therefore, the present study evaluated its effectiveness in the surgical management of large parastomal hernias.

Patients and Methods:

This prospective, observational study included 23 consecutive patients with large parastomal hernias who underwent PPP between January 2016 and September 2018. The volume of parastomal hernia (VPH), volume of the abdominal cavity (VAC), and the VPH/VAC ratio were measured before and after PPP using abdominal computed tomography scan data. All the hernias were repaired by a laparoscopic or laparoscopic-open-laparoscopic approach using the intraperitoneal Sugarbaker technique.

Results:

Before and after PPP, the mean VPH was 1442 and 1581 mL (P<0.01), and the mean VAC was 5667 and 9194 mL (P<0.01). The VAC increased by 3527 mL (P<0.01) and was greater than the mean VPH before PPP. The VPH/VAC ratio after PPP was reduced at an average of 8.1% (P<0.01). Fascial closure was achieved in all patients, with no clinical evidence of elevated intra-abdominal pressures. The mean follow-up was 24 months (13 to 40 mo), and, to date, no hernia recurrences have been reported in these patients.

Conclusions:

PPP is a feasible and useful tool in the surgical management of large parastomal hernias. It passively expands the abdominal volumes, thereby resulting in respiratory adaptation to elevated intra-abdominal pressures.
Hand-assisted Laparoscopic Repeat Hepatectomy for Secondary Liver Neoplasm
Authors: Mahamid Ahmad , Berger Yael , Halim Nasser A. , Goldberg Natalia , Sawaied Muneer , Bitterman Arie , Sadot Eran , Haddad Riad
Published: January 2020

Background:

Hand-assisted laparoscopic surgery is a widely accepted alternative to an open approach. The use of this technique in repeat liver resection is limited due to technical difficulties caused by postsurgical adhesions. We aimed to assess the feasibility and safety of hand-assisted laparoscopic repeat hepatectomy (HALRH).

Materials and Methods:

This was a retrospective study of the medical files of patients who had undergone HALRH between 2010 and 2017 in 2 university-affiliated medical centers.

Results:

Sixteen patients with repeat hepatectomy were included with a median age of 67.5 years. The first liver resection was a traditional laparotomy for 9 patients and hand-assisted laparoscopic surgery for 7 patients. The conversion rate to open surgery was 6%. The median operative time, blood loss during surgery, and postoperative hospital stay were 166 minutes, 400 mL, and 7 days, respectively. R0 resections were achieved in 88% of patients. The median number of tumors and tumor size were 1 and of 25 mm, respectively. There were no mortalities or major complications postoperatively. For patients with colorectal liver metastases, the median follow-up and overall survival were 21 and 43 months, respectively.

Conclusion:

The findings suggest HALRH to be safe and feasible. Future ERAS guidelines should evaluate this approach for liver surgery.
Adjunctive use of hepatic angioembolization following hemorrhage control laparotomy
Authors: Matsushima Kazuhide , Hogen Rachel , Piccinini Alice , Biswas Subarna , Khor Desmond , Delapena Samantha , Strumwasser Aaron , Inaba Kenji , Demetriades Demetrios
Published: January 2020

BACKGROUND

Severe liver injuries pose a challenge to trauma surgeons. While the use of hepatic angioembolization (HAE) has been evaluated as a component of the nonoperative management of liver injury, little is known about the efficacy of postoperative HAE in patients who require hemorrhage control laparotomy (HCL) for liver injury. The purpose of this study is to evaluate the impact of HAE following HCL on patient survival.

METHODS

This is a retrospective cohort study using the American College of Surgeons Trauma Quality Improvement Program database from January 2013 to December 2014. In propensity score matched (2:1) patients who underwent HCL-only or HCL + HAE, the impact of adjunctive use of HAE on patient survival was examined with the Cox proportional hazards regression analysis adjusting for transfusion requirement within 4 hours. We also performed a subgroup analysis in patients without severe traumatic brain injury (Abbreviated Injury Scale head ≤3).

RESULTS

A total of 1,675 patients met our inclusion criteria. Of those, 75 (4.5%) patients underwent HAE after HCL (median hours to HAE, 5 hours after admission). In 225 propensity score-matched patients, the use of HAE following HCL was significantly associated with improved 24-hour mortality, but not in-hospital mortality. In the subgroup of patients without severe traumatic brain injury (n = 189), we observed significant survival benefits (24-hour and in-hospital mortality) associated with the adjunctive use of HAE.

CONCLUSION

The results of our study suggest that the adjunctive use of HAE might improve survival of patients who require HCL for liver injury. Further prospective study to determine the indication for postoperative HAE is still warranted.

LEVEL OF EVIDENCE

Therapeutic study, level III.
Natural language processing of prehospital emergency medical services trauma records allows for automated characterization of treatment appropriateness
Authors: Tignanelli Christopher J. , Silverman Greg M. , Lindemann Elizabeth A. , Trembley Alexander L. , Gipson Jon C. , Beilman Gregory , Lyng John W. , Finzel Raymond , McEwan Reed , Knoll Benjamin C. , Pakhomov Serguei , Melton Genevieve B.
Published: January 2020

BACKGROUND

Incomplete prehospital trauma care is a significant contributor to preventable deaths. Current databases lack timelines easily constructible of clinical events. Temporal associations and procedural indications are critical to characterize treatment appropriateness. Natural language processing (NLP) methods present a novel approach to bridge this gap. We sought to evaluate the efficacy of a novel and automated NLP pipeline to determine treatment appropriateness from a sample of prehospital EMS motor vehicle crash records.

METHODS

A total of 142 records were used to extract airway procedures, intraosseous/intravenous access, packed red blood cell transfusion, crystalloid bolus, chest compression system, tranexamic acid bolus, and needle decompression. Reports were processed using four clinical NLP systems and augmented via a word2phrase method leveraging a large integrated health system clinical note repository to identify terms semantically similar with treatment indications. Indications were matched with treatments and categorized as indicated, missed (indicated but not performed), or nonindicated. Automated results were then compared with manual review, and precision and recall were calculated for each treatment determination.

RESULTS

Natural language processing identified 184 treatments. Automated timeline summarization was completed for all patients. Treatments were characterized as indicated in a subset of cases including the following: 69% (18 of 26 patients) for airway, 54.5% (6 of 11 patients) for intraosseous access, 11.1% (1 of 9 patients) for needle decompression, 55.6% (10 of 18 patients) for tranexamic acid, 60% (9 of 15 patients) for packed red blood cell, 12.9% (4 of 31 patients) for crystalloid bolus, and 60% (3 of 5 patients) for chest compression system. The most commonly nonindicated treatment was crystalloid bolus (22 of 142 patients). Overall, the automated NLP system performed with high precision and recall with over 70% of comparisons achieving precision and recall of greater than 80%.

CONCLUSION

Natural language processing methodologies show promise for enabling automated extraction of procedural indication data and timeline summarization. Future directions should focus on optimizing and expanding these techniques to scale and facilitate broader trauma care performance monitoring.

LEVEL OF EVIDENCE

Diagnostic tests or criteria, level III.
The Influence of Antithymocyte Globulin Dose on the Incidence of CMV Infection in High-risk Kidney Transplant Recipients Without Pharmacological Prophylaxis
Authors: de Paula Mayara I. , Bae Sunjae , Shaffer Ashton A. , Garonzik-Wang Jacqueline , Felipe Claudia R. , Cristelli Marina P. , Waldram Madeleine M. , Massie Allan B. , Medina-Pestana Jose , Segev Dorry L. , Tedesco-Silva Helio
Published: January 2020

Background.

Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis.

Methods.

We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1–1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose.

Results.

Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose.

Conclusions.

In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.
Pretransplant NT-proBNP, Dialysis Vintage, and Posttransplant Mortality in Kidney Transplant Recipients
Authors: Yeung Stanley M.H. , van Londen Marco , Nakshbandi Uzma , Said M. Yusof , Eisenga Michele F. , Hepkema Bouke G. , Nolte Ilja M. , Berger Stefan P. , de Borst Martin H. , Bakker Stephan J.L.
Published: January 2020

Background.

End-stage kidney disease and dialysis vintage are characterized by accelerated atherosclerosis, volume overload, and progressive left ventricular hypertrophy, leading to elevated N-terminal probrain natriuretic peptide (NT-proBNP) levels. Pretransplant dialysis vintage is associated with excess mortality after transplantation. We want to study whether pretransplant NT-proBNP is associated with posttransplantation mortality and if it explains the association of dialysis vintage with posttransplantation mortality in kidney transplant recipients (KTR).

Methods.

We measured plasma NT-proBNP on arrival at the hospital before kidney transplantation in 658 KTR between January 1995 and December 2005 in our center. Multivariable Cox regression analyses, adjusted for potential confounders, were used to prospectively study the associations of dialysis vintage and NT-proBNP with all-cause mortality.

Results.

During median 12.7 (7.8–15.6) years of follow-up after transplantation, 248 (37.7%) KTR died. Dialysis vintage was associated with an increased risk of posttransplant mortality in the fully adjusted model (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.03-1.43; P = 0.02), independent of potential confounders. The association weakened materially and lost significance after further adjustment for NT-proBNP (HR, 1.14; 0.96–1.34; P = 0.14). NT-proBNP was independently associated with all-cause mortality in the fully adjusted model (HR, 1.34; 1.16–1.55; P < 0.001). The association remained independent of adjustment for dialysis vintage (HR, 1.31; 1.13–1.52; P < 0.001).

Conclusions.

Our study shows that longer dialysis vintage is associated with a higher mortality risk in KTR, and this association might be explained for a considerable part by variation in pretransplant NT-proBNP at the time of transplantation.
Breach Rhythm May Be Suppressed as a Form of Todd's Paralysis
Authors: Lyudmilov Cristina , Petersone Daina , Schmidt Christian , Bösel Julian , Rösche Johannes
Published: January 2020

This case report will provide further evidence for the fact that breach rhythm is not the effect of a bone abnormality only. We present the case of an 84–year-old woman, who had a craniotomy 14 month before admission to our emergency department with a focal inhibitory status epilepticus. Even after clinical recovery, electroencephalography revealed frequent subclinical seizure patterns. When seizure activity was suppressed by anticonvulsive medication with levetiracetam, breach rhythm appeared. Breach rhythm develops usually some months after craniotomy and therefore should have been established in our patient at the time of admission. Therefore, it is reasonable to assume that it was in some way suppressed by the seizure activity in our primary EEG recordings. The appearance of the breach rhythm after the complete suppression of seizure activity by antiepileptic drug treatment shows that breach rhythm is not purely the result of a skull defect but is related to the functional state of the brain tissue beneath.
Mangrovimonas spongiae sp. nov., a novel member of the genus Mangrovimonas isolated from marine sponge
Authors: Zhuang Lingping , Lin Binbin , Luo Lianzhong
Published: January 2020

A taxonomic study was carried out on strain HN-E26T, which was isolated from sponge collected from Yangpu Bay, Hainan, PR China. Cells of strain HN-E26T were Gram-stain-negative, motile by gliding, yellow-pigmented and rod-shaped. The strain could grow at 10–40 °C (optimum, 25 °C), at pH 6.0–9.0 (optimum, pH 7.0) and in 0.5–12 % (w/v) NaCl (optimum, 4–7 %). This isolate was positive for oxidase, catalase, and the hydrolysis of starch, xylan, aesculin and gelatin, but negative for indole production and the reduction of nitrate. Strain HN-E26T shared the highest 16S rRNA gene sequence similarity with

Mangrovimonas yunxiaonensis

LYYY01T (95.5 %), followed by

Formosa spongicola

A2T (94.4 %),

Meridianimaribacter flavus

NH57NT (94.3 %) and

Winogradskyella exilis

022-2-26T (94.3 %). The phylogenetic tree based on 16S rRNA gene sequences revealed that strain HN-E26T formed a distinct phylogenetic lineage within the cluster comprising

Mangrovimonas yunxiaonensis

LYYY01T and ‘

Mangrovimonas xylaniphaga

’ ST2L12T. The dominant fatty acids were iso-C15 : 0 and iso-C15 : 1 G. The major polar lipids comprised phosphatidylethanolamine, three unidentified aminolipids and six unidentified lipids. The respiratory lipoquinone was identified as MK-6. The G+C content of the genomic DNA was 33.9 mol%. Based on the phenotypic and phylogenetic data, strain HN-E26T represents a novel species of the genus

Mangrovimonas

, for which the name Mangrovimonas spongiae sp. nov. is proposed, with the type strain HN-E26T (=MCCC 1K03326T=LMG 30458T).
Immunotherapy Implication of Signature-Guided Biomarker Discovery for Trastuzumab-Resistant HER2-Positive Breast Cancer
Authors: Sand Andrea , Duffin Aspen T. , Riddell Geoffrey T. , Piacsek Mitchel , Last Brittany , Sun Chaoyang , Rovin Richard A. , Tjoe Judy A. , Yin Jun
Published: January 2020

Despite the great improvement of patient outcomes by trastuzumab, a monoclonal antibody targeted on HER2-positive breast cancer, approximately 23% of patients with early-stage disease treated with adjuvant trastuzumab either fail to respond or experience recurrence within 10 years, highlighting the importance of identifying which HER2-positive patients would benefit from trastuzumab upfront. Efforts to identify biomarkers predictive of response to trastuzumab in initial breast tumor core biopsies have been complicated by the clinical and biological heterogeneity of HER2-positive tumors. Therefore, we identified a trastuzumab-resistant (TrR) signature that accurately predicts response to trastuzumab quantitively and qualitatively in vitro and in vivo, via repurposing transcriptome profiles in an engineered cell line model. We additionally demonstrated that our TrR signature was associated with tumor progression and capable of stratifying patient prognosis. Our study further illustrated the possible mechanism of this resistance as being less inherited cytotoxic T cell infiltration and failure to secrete Interferon-γ upon trastuzumab treatment in TrR tumors. These findings highlight the potential clinical application of TrR signature in treatment management and identifying possible immunotherapy interventions.
Machine Learning Approaches for the Prediction Bone Mineral Density by using genomic and phenotypic data of 5,130 older Men
Authors: Wu Qing , Nasoz Fatma , Jung Jongyun , Bhattarai Bibek , Han Mira V
Published: January 2020

Background

The study aimed to utilize machine learning (ML) approaches and genomic data to develop the prediction model for bone mineral density (BMD), and to identify the best modeling approach for BMD prediction.

Method

The genomic and phenotypic data of Osteoporotic Fractures in Men Study (n=5,130), was analyzed. Genetic risk score (GRS) was calculated from 1,103 associated SNPs for each participant after a comprehensive genotype imputation. Data were normalized and divided into a training set (80%) and a validation set (20%) for analysis. Random forest, gradient boosting, neural network, and linear regression were used to develop prediction models for BMD separately. The 10-fold cross-validation was used for hyperparameter optimization. Mean square error and mean absolute error were used to assess model performance. Results: When using GRS and phenotypic covariates as the predictors, the performance of all ML models and linear regression in BMD prediction is similar. However, when replacing GRS with the 1,103 individual SNPs in the model, ML models performed significantly better than linear regression, and the gradient boosting model performed the best. Conclusion: Our study suggested that ML models, especially gradient boosting, can improve BMD prediction in genomic data.
A single nucleotide substitution inTaHKT1;5-Dcontrols shoot Na+accumulation in bread wheat
Authors: Borjigin Chana , Schilling Rhiannon K. , Bose Jayakumar , Hrmova Maria , Qiu Jiaen , Wege Stefanie , Situmorang Apriadi , Brien Chris , Berger Bettina , Gilliham Matthew , Pearson Allison S. , Roy Stuart J.
Published: January 2020

Improving salinity tolerance in the most widely cultivated cereal, bread wheat (Triticum aestivumL.), is essential to increase grain yields on saline agricultural lands. A Portuguese landrace, Mocho de Espiga Branca accumulates up to 6 folds greater leaf and sheath sodium (Na+) than two Australian cultivars, Gladius and Scout, under salt stress. Despite high leaf and sheath Na+concentrations, Mocho de Espiga Branca maintained similar salinity tolerance compared to Gladius and Scout. A naturally occurring single nucleotide substitution was identified in the gene encoding a major Na+transporter TaHKT1;5-D in Mocho de Espiga Branca, which resulted in a L190P amino acid residue variation. This variant prevents Mocho de Espiga Branca from retrieving Na+from the root xylem leading to a high shoot Na+concentration. The identification of the tissue tolerant Mocho de Espiga Branca will accelerate the development of more elite salt tolerant bread wheat cultivars.
High-throughput microCT scanning of small specimens: preparation, packing, parameters and post-processing
Authors: Hipsley Christy A. , Aguilar Rocio , Black Jay R. , Hocknull Scott A.
Published: January 2020

High-resolution X-ray microcomputed tomography, or microCT (μCT), enables the digital imaging of whole objects in three dimensions. The power of μCT to visualise internal features without disarticulation makes it particularly valuable for the study of museum collections, which house millions of physical specimens documenting the spatio-temporal patterns of life. Despite its potential for comparative analyses, most μCT studies include limited numbers of museum specimens, due to the challenges of digitising numerous individuals within a project scope. Here we describe a method for high-throughput μCT scanning of hundreds of small (< 2 cm) specimens in a single container, followed by individual labelling and archival storage. We also explore the effects of various packing materials and multiple specimens per capsule to minimize sample movement that can degrade image quality, and hence μCT investment. We demonstrate this protocol on vertebrate fossils from Queensland Museum, Australia, as part of an effort to track community responses to climate change over evolutionary time. This system can be easily modified for other types of wet and dry material amenable to X-ray attenuation, including geological, botanical and zoological samples, providing greater access to large-scale phenotypic data and adding value to global collections.
Novel Type 2-high gene clusters associated with corticosteroid sensitivity in COPD
Authors: Faiz A. , Pavlidis S. , Kuo C.S. , Rowe A. , Hiemstra P. S. , Timens W. , Berg M. , Wisman M. , Guo Y. , Djukanovic R. , Sterk P. J. , Nawijn M.C. , Adcock I. M. , Chung K. F. , van den Berge M.
Published: January 2020

Rationale

Severe asthma and COPD share common pathophysiologic traits such as relative corticosteroid insensitivity. We recently published three transcriptome-associated clusters (TACs) using hierarchical analysis of the sputum transcriptome in asthmatics from the U-BIOPRED cohort with one Type 2-high signature (TAC1) and 2 Type 2-low signatures.

Objective

We examined whether gene-expression signatures obtained in asthma can be used to identify the subgroup of COPD patients with steroid sensitivity.

Methods

Using gene set variation analysis (GSVA), we examined the distribution and enrichment scores (ES) of the 3 TACs in the transcriptome of bronchial biopsies from 46 patients who participated in the GLUCOLD COPD study that received 30 months of treatment with inhaled corticosteroids (ICS) with and without an added long-acting β-agonist (LABA). The identified signatures were then associated with longitudinal clinical variables after treatment.

Measurements and main results

Bronchial biopsies in COPD patients at baseline showed a wide range of expression of the 3 TACs. After ICS±LABA treatment, the ES of TAC1 was significantly reduced at 30 months, but those of TAC2 and TAC3 were unaffected. A corticosteroid-sensitive TAC1 (sub)signature was developed from the TAC1 ICS-responsive genes. This signature consisted of mast cell-specific genes identified by single-cell RNA-seq and positively correlated with bronchial biopsy mast cell numbers following ICS±LABA. Baseline levels of gene transcription predicted change in FEV1 %predicted following 30-month ICS±LABA.

Conclusions

Sputum-derived transcriptomic signatures from an asthma cohort can be recapitulated in bronchial biopsies of COPD patients and identified airway wall mast cells as a predictor of those COPD patients who will benefit from inhaled corticosteroids.
Allele mining unlocks the identification of RYMV resistance genes and alleles in African cultivated rice
Authors: Pidon Hélène , Chéron Sophie , Ghesquière Alain , Albar Laurence
Published: January 2020

Background

Rice yellow mosaic virus(RYMV) is a major rice pathogen in Africa. Three resistance genes, i.e.RYMV1,RYMV2andRYMV3,have been previously described.RYMV1encodes the translation initiation factor eIF(iso)4G-1 and the best candidate genes forRYMV2andRYMV3encode a homolog of anArabidopsisnucleoporin (CPR5) and a nucleotide-binding domain and leucine-rich repeat containing domain (NLR) protein, respectively. High resistance is very uncommon in Asian cultivated rice (Oryza sativa), with only two highly resistant accessions identified so far, but it is more frequent in African cultivated rice (Oryza glaberrima).

Results

Here we report the findings of a resistance survey in a reference collection of 268O. glaberrimaaccessions. A total of 40 resistant accessions were found, thus confirming the high frequency of resistance to RYMV in this species. We analysed the variability of resistance genes or candidate genes in this collection based on high-depth Illumina data or Sanger sequencing. Alleles previously shown to be associated with resistance were observed in 31 resistant accessions but not in any susceptible ones. Five original alleles with a frameshift or untimely stop codon in the candidate gene forRYMV2were also identified in resistant accessions. A genetic analysis revealed that these alleles, as well as T-DNA insertions in the candidate gene, were responsible of RYMV resistance. All 40 resistant accessions were ultimately linked to a validated or candidate resistance allele at one of the three resistance genes to RYMV.

Conclusion

This study demonstrated that theRYMV2resistance gene is homologous to theArabidopsis CPR5gene and revealed five new resistance alleles at this locus. It also confirmed the close association between resistance and an amino-acid substitution in the leucine-rich repeat of the NLR candidate forRYMV3. We also provide an extensive overview of the genetic diversity of resistance to RYMV in theO. glaberrimaspecies, while underlining the contrasted pattern of diversity betweenO. glaberrimaandO. sativafor this trait. The different resistance genes and alleles will be instrumental in breeding varieties with sustainable field resistance to RYMV.
Potential depression and antidepressant-response biomarkers in human lymphoblast cell lines from treatment-responsive and treatment-resistant subjects: roles of SSRIs and omega-3 polyunsaturated fatty acids
Authors: Chukaew Phatcharee , Leow Alex , Saengsawang Witchuda , Rasenick Mark M.
Published: January 2020

While several therapeutic strategies exist for depression, most antidepressant drugs require several weeks before reaching full biochemical efficacy and remission is not entirely achieved in many patients. Therefore, biomarkers for depression and drug-response would help tailor treatment strategies. This study made use of banked human lymphoblast cell lines (LCLs) from normal and depressed subjects; the latter divided into remitters and non-remitters. Due to the fact that previous studies have shown effects on growth factors, cytokines and elements of the cAMP generating system as potential biomarkers for depression and antidepressant action, these were examined in LCLs. Initial gene and protein expression profiles for signaling cascades related to neuroendocrine and inflammatory functions differ among the three groups. Growth factor genes, includingVEGFAandBDNFwere significantly down-regulated in cells from depressed subjects. In addition, omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to act as both antidepressants and anti-inflammatories, but the mechanisms for these effects are not established. Here we showed that n-3 PUFAs and escitalopram (selective serotonin reuptake inhibitors, SSRIs) treatment increased adenylyl cyclase (AC) andBDNFgene expression in LCLs. These data are consistent with clinical observations showing that n-3 PUFA and SSRI have antidepressant affects, which may be additive. Contrary to observations made in neuronal and glial cells, n-3 PUFA treatment attenuated cAMP accumulation in LCLs. However, while lymphoblasts show paradoxical responses to neurons and glia, patient-derived lymphoblasts appear to carry potential depression biomarkers making them an important tool for studying precision medicine in depressive patients. Furthermore, these data validate usefulness of n-3 PUFAs in treatment for depression.
C. elegansestablishes germline versus soma by balancing inherited histone methylation
Authors: Carpenter Brandon S. , Lee Teresa W. , Plott Caroline F. , Brockett Jovan S. , Myrick Dexter A. , Katz David J.
Published: January 2020

Embryos undergo extensive reprogramming at fertilization to prevent the inappropriate inheritance of histone methylation. InC. elegans,this reprogramming is mediated by the H3K4me2 demethylase, SPR-5, and the H3K9 methyltransferase, MET-2. In contrast to this reprogramming, the H3K36 methyltransferase, MES-4, maintains H3K36me2/3 at germline genes between generations to help re-establish the germline. To determine whether the MES-4 germline inheritance system antagonizesspr-5; met-2reprogramming, we examined the interaction between these two systems. We find that the developmental delay ofspr-5; met-2mutant progeny is associated with ectopic H3K36me2/3 and the ectopic expression of MES-4 targeted germline genes in somatic tissues. Furthermore, the developmental delay is dependent upon MES-4 and the H3K4 methyltransferase, SET-2. We propose that the MES-4 inheritance system prevents critical germline genes from being repressed by maternalspr-5; met-2reprogramming. Thus, the balance of inherited histone modifications is necessary to distinguish germline versus soma and prevent developmental delay.
The self-face captures attention without consciousness: evidence from the N2pc ERP component analysis
Authors: Bola Michał , Paź Marta , Doradzińska Łucja , Nowicka Anna
Published: January 2020

It is well established that stimuli representing or associated with ourselves, like our own name or an image of our own face, benefit from preferential processing. However, two key questions concerning the self-prioritization mechanism remain to be addressed. First, does it operate in an automatic manner during the early processing, or rather in a more controlled fashion at later processing stages? Second, is it specific to the self-related stimuli, or can it be activated also by other stimuli that are familiar or salient? We conducted a dot-probe experiment to investigate the mechanism behind attentional prioritization of the selfface image and to tackle both questions. The former, by employing a backwards masking procedure to isolate the early and preconscious processing stages. The latter, by investigating whether a face that becomes visually familiar due to repeated presentations is able to capture attention in a similar manner as the self-face. Analysis of the N2pc ERP component revealed that the self-face image automatically captures attention, both when processed consciously and unconsciously. In contrast, the visually familiar face did not attract attention, neither in the conscious, nor in the unconscious condition. We conclude that the selfprioritization mechanism is early and automatic, and is not triggered by a mere visual familiarity. More generally, our results provide further evidence for efficient unconscious processing of faces, and for a dissociation between attention and consciousness.
Substrate Channelingviaa Transient Protein-Protein Complex: The case of D-Glyceraldehyde-3-Phosphate Dehydrogenase and L-Lactate Dehydrogenase
Authors: Svedružić Željko M. , Odorčić Ivica , Chang Christopher H. , Svedružić Draženka
Published: January 2020

Background

D-Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and L-lactate dehydrogenase (LDH) can form a complex that can regulate the major metabolic pathways, however, the exact mechanism remains unknown. We analyzed a possibility of NADH-channeling from GAPDH-NADH complex to LDH isozymes using enzymes from different cells.

Results

Enzyme-kinetics and NADH-binding studies showed that LDH can use GAPDH-NADH complex as a substrate. LDH activity with GAPDH-NADH complex was challenged with anti-LDH antibodies to show that the channeled and the diffusive reactions always take place in parallel. The channeling path is dominant only in assays with limiting free-NADH concertation that mimic cytosolic conditions. Analytical ultracentrifugation showed that the channeling does not require a high affinity complex. Molecular dynamics calculations and protein-protein interaction studies showed that LDH and GAPDH can form a leaky channeling complex only at subsaturating NADH concentrations. The interaction sites are conserved between LDH isozymes from heart and muscle, and between GAPDH molecules from rabbit and yeast cells. Positive electric fields between the NAD(H) binding sites on LDH and GAPDH tetramers, showed that NAD(H)-channeling within the LDH-GAPDH complex, can be an extension of NAD(H)-channeling between the adjacent subunits in each tetramer.

Conclusions

In the case of a transient (GAPDH-NADH)-LDH complex, the relative contribution from the channeled and the diffusive paths depends on the overlap betweenoff-rates for the transient (GAPDH-NADH)-LDH complex andoff-rates for the GAPDH-NADH complex. Molecular evolution or metabolic engineering protocols can exploit substrate channeling for metabolic flux control by fine-tuning substrate-binding affinity for the key enzymes in the competing reaction paths.

Highlights

- Substrate channeling molecular mechanism can regulate energy production and aerobic and anaerobic metabolism in cells

- LDH and GAPDH can form a channeling complex only at sub-saturating NADH concentration

- Channeled and diffusive paths always compete and take place in parallel

- NADH channeling does not require a high-affinity complex

- NADH channeling within GAPDH-LDH complex is an extension of NAD(H) channeling within each tetramer

- Allosteric modulation of NADH binding affinity in GAPDH tetramer can regulate NAD(H) channeling
Single-molecule orientation localization microscopy for resolving structural heterogeneities between amyloid fibrils
Authors: Ding Tianben , Wu Tingting , Mazidi Hesam , Zhang Oumeng , Lew Matthew D.
Published: January 2020

Simultaneous measurements of single-molecule positions and orientations provide critical insight into a variety of biological and chemical processes. Various engineered point spread functions (PSFs) have been introduced for measuring the orientation and rotational diffusion of dipole-like emitters, but the widely used Cramér-Rao bound (CRB) only evaluates performance for one specific orientation at a time. Here, we report a performance metric, termed variance upper bound (VUB), that yields a global maximum CRB for all possible molecular orientations, thereby enabling the measurement performance of any PSF to be computed efficiently (~1000× faster than calculating average CRB). Our VUB reveals that the simple polarized standard PSF provides robust and precise orientation measurements if emitters are near a refractive index interface. Using this PSF, we measure the orientations and positions of Nile red (NR) molecules transiently bound to amyloid aggregates. Our super-resolved images reveal the main binding mode of NR on amyloid fiber surfaces, as well as structural heterogeneities along amyloid fibrillar networks, that cannot be resolved by single-molecule localization alone.
N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells
Authors: Yu Jiang-Zhou , Wang Jennifer , Sheridan Steven D. , Perlis Roy H. , Rasenick Mark M.
Published: January 2020

Evidence from epidemiological and laboratory studies, as well as randomized placebo-controlled trials, suggests supplementation with n-3 polyunsaturated fatty acids (PUFAs) may be efficacious for treatment of major depressive disorder (MDD). The mechanisms underlying n-3 PUFAs potential therapeutic properties remain unknown. There are suggestions in the literature that glial hypofunction is associated with depressive symptoms and that antidepressants may normalize glial function. In this study, iPSC-derived neuronal stem cell lines were generated from individuals with MDD. Astrocytes differentiated from patient-derived neuronal stem cells (iNSCs) were verified by GFAP. Cells were treated with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and stearic acid (SA). During astrocyte differentiation, we found that n-3 PUFAs increased GFAP expression and GFAP positive cell formation. BDNF and GDNF production were increased in the astrocytes derived from patients subsequent to n-3 PUFA treatment. Stearic Acid (SA) treatment did not have this effect. CREB activity (phosphorylated CREB) was also increased by DHA and EPA but not by SA. Furthermore, when these astrocytes were treated with n-3 PUFAs, the cAMP antagonist, RP-cAMPs did not block n- 3 PUFA CREB activation. However, the CREB specific inhibitor (666-15) diminished BDNF and GDNF production induced by n-3 PUFA, suggesting CREB dependence. Together, these results suggested that n-3 PUFAs facilitate astrocyte differentiation, and may mimic effects of some antidepressants by increasing production of neurotrophic factors. The CREB-dependence and cAMP independence of this process suggests a manner in which n-3 PUFA could augment antidepressant effects. These data also suggest a role for astrocytes in both MDD and antidepressant action.
CIRFESS: An interactive resource for querying the set of theoretically detectable peptides for cell surface and extracellular enrichment proteomic studies
Authors: Waas Matthew , Littrell Jack , Gundry Rebekah L.
Published: January 2020

Cell surface transmembrane, extracellular, and secreted proteins are high value targets for immunophenotyping, drug development, and studies related to intercellular communication in health and disease. As the number of specific and validated affinity reagents that target this subproteome are limited, mass spectrometry (MS)-based approaches will continue to play a critical role in enabling discovery and quantitation of these molecules. Given the technical considerations that make MS-based cell surface proteome studies uniquely challenging, it can be difficult to select an appropriate experimental approach. To this end, we have integrated multiple prediction strategies and annotations into a single online resource,CompiledInteractiveResourceforExtracellular andSurfaceStudies (CIRFESS). CIRFESS enables rapid interrogation of the human proteome to reveal the cell surface proteome theoretically detectable by current approaches and highlights where current prediction strategies provide concordant and discordant information. We applied CIRFESS to identify the percentage of various subsets of the proteome which are expected to be captured by targeted enrichment strategies, including two established methods and one that is possible but not yet demonstrated. These results will inform the selection of available proteomic strategies and development of new strategies to enhance coverage of the cell surface and extracellular proteome. CIRFESS is available atwww.cellsurfer.net/cirfess.