bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical signs of retroperitoneal abscess from colonic perforation
Authors: Ruscelli Paolo , Renzi Claudio , Polistena Andrea , Sanguinetti Alessandro , Avenia Nicola , Popivanov Georgi , Cirocchi Roberto , Lancia Massimo , Gioia Sara , Tabola Renata
Published: November 2018

Rationale:

Retroperitoneal colonic perforation is a rare cause of retroperitoneal abscess. It presents, more frequently in frail elderly patients, with heterogeneous signs and symptoms which hamper the clinical diagnosis. Subcutaneous emphysema with pneumomediastinum and iliopsoas muscle abscess are unusual signs. Colonic retroperitoneal perforation may be consequent to diverticulitis or locally advanced colon cancer. Due to the anatomy of the retroperitoneal space and different physiopathology, diverticular perforation may present with air and pus collection; on the other hand perforated colon cancer may cause groin mass and psoas abscess. We reported 2 cases of colonic retroperitoneal perforation from diverticulitis and locally advanced colon cancer, respectively. Aim of this report is to improve differential diagnosis based on clinical signs.

Patients’ concerns:

A 71-year-old man presented with pain in his left side, fatigue, fever, nausea, massive subcutaneous emphysema of the neck, and Blumberg sign in the left iliac fossa. A 67-year-old man presented with abdominal pain, sub-occlusion, left groin mass, left groin, and lower limb pain during walking, negative Blumberg sign.

Diagnosis:

In the first patient the computerized tomography revealed pneumoperitoneum, gas in the mesosigma, pneumomediastinum, wall thickening of the descending colon, and retroperitoneal collection from diverticular perforation. In the second patient abdominal CT scan found thickening of the sigmoid colon adherent to the iliopsoas and fluid collection.

Interventions:

In the first patient, a left hemicolectomy extending to the transverse colon, followed by a toilette and debridement of the retroperitoneum were performed. In the second patient, tumor of descending colon perforated in the retroperitoneum with iliopsoas abscess was treated with left hemicolectomy and a drainage of the abscess.

Outcomes:

The first patient underwent right colectomy with ileostomy in the 7th postoperative day for large bowel necrosis. He died of sepsis 2 days after. The second patient had regular postoperative and he is still alive.

Lessons:

The spread of retroperitoneal abscess in complicated colonic diverticulitis is different from that in advanced colonic cancer. The former can present with a subcutaneous emphysema, the latter with a groin mass. Hence a thorough clinical examination and radiological studies are needed to diagnose these conditions.
Retrospective analysis of 52 patients with prolactinomas following endoscopic endonasal transsphenoidal surgery
Authors: Han Yan-Long , Chen Dong-Ming , Zhang Cheng , Pan Miao , Yang Xiao-Peng , Wu Yong-Gang
Published: November 2018

Background:

Prolactinomas affect patients’ quality of life and even endanger lives. The study aimed to investigate the effect of the endoscopic endonasal transsphenoidal approach (EETA) on 52 patients with prolactinomas.

Methods:

A total of 52 patients with prolactinomas who had previously undergone EETA in the People's Hospital of Xinjiang Uygur Autonomous Region between January 2013 and December 2017 were retrospectively analyzed. Factors affecting the extent of resection and postoperative remission rates were also investigated.

Results:

All the patients were pathologically diagnosed with prolactinomas. Compared with giant adenomas, the total removal rate of microadenomas and macroadenomas was significantly increased (P < .05). In addition, the total removal rate of patients with noninvasive prolactin adenomas was significantly higher than patients with invasive prolactinadenomas (P < .05). Furthermore, there were no significant differences in postoperative remission rates among patients with prolactin adenomas from different ethnic groups (P > .05). Also preoperative administration of bromocriptine and preoperative prolactin (PRL) levels did not significantly affect therapeutic outcomes postsurgery (P > .05). Postoperative menstruation was improved or normalized in 20 (38.5%) female patients, vision was improved or normalized in 15 (28.8%) patients, and headaches were improved or normalized in 22 (42.3%) patients. Sexual function was improved in 2 male patients following surgery. A total of 6 patients exhibited a recurrence following surgery. A number of patients suffered from postoperative complications, including transient diabetes insipidus in 5 (9.6%) patients and postoperative transient cerebrospinal fluid leakage in 2 (3.8%) patients.

Conclusion:

The results of this study demonstrated that tumor size, preoperative PRL levels, and invasion of adenomas represent independent factors that can affect the success of surgery. The results suggested that EETA represents a therapeutic strategy for the treatment of patients with prolactinoma with high remission rates and low complication rates. Therefore, EETA should be considered a primary treatment for patients with prolactinomas who are not responsive to treatment with medical therapy.
Different weight shift trainings can improve the balance performance of patients with a chronic stroke
Authors: Liao Wan-Chun , Lai Chung-Liang , Hsu Pi-Shan , Chen Kun-Chung , Wang Chun-Hou
Published: November 2018

Background:

Improving balance ability, increasing walking ability, and reducing the occurrence of falls are important objectives in the rehabilitation of stroke patients. Do the posture balance training and the intervention of lateral wedge insoles to improve of balance function and increase walking ability in patients with a chronic stroke?

Methods:

A randomized, controlled trial with concealed allocation, intention-to-treat analysis, and blinded assessors. Participants who had a chronic stroke (onset >6 months) were recruited from the rehabilitation and neurology departments of a hospital in central Taiwan. Subjects were divided into 3 groups: a visual biofeedback balance training group, a lateral wedge group, and a control group; apart from their usual rehabilitation program, and both experimental groups received a 6-week training session program. The primary outcome was the balance computerized adaptive test (balance CAT), and secondary outcome was timed up and go (TUG) test. All subjects were evaluated at the baseline, posttraining (6-week), 1st follow-up (10-week), and 2nd follow-up (18-week).

Results:

A total of 56 subjects were participated in this study, including 38 males and 18 females. The mean age of the subjects was 59.1 years old, and the mean time was 43.7 months after the onset of the stroke. This study found the interaction in groups and measurement time points reached statistical significance of the balance CAT and TUG test (F = 5.740, P < .001; F = 2.926, P = .011; respectively). In addition, the performance of both the visual biofeedback training and lateral wedge group was superior to that of the control group.

Conclusion:

Six-week visual biofeedback training and intervention of 5° lateral wedge insoles can improve the balance ability of patients with a chronic stroke.

Trial registry:

http://www.chictr.org.cn, ChiCTR-IPR-15007092.
Vaginal delivery in a pregnant woman with cord prolapse, velamentous cord insertion, and fetal vertex presentation
Authors: Li Pei-Chen , Ding Dah-Ching
Published: November 2018

Rationale:

We report a rare case of a pregnant woman with cord prolapse, velamentous cord insertion (VCI), and fetal vertex presentation who completed vaginal delivery.

Patient concerns:

Without having undergone regular antepartum examinations, a 31-year-old pregnant woman, gravida 6, para 4, abortion 1, presented at 37 weeks and 3 days of gestation. She had regular labor pain and bloody show.

Diagnoses:

Cord prolapse during labor and VCI after delivery.

Interventions:

Per vaginal examination at 11:20 pm revealed a fully dilated cervix. Thirty minutes later, artificial rupture of the membrane was performed, and an overt prolapsed cord approximately 10-cm long was palpated in the vagina. Fetal heartbeat decelerated to 60 bpm. After fundal pushing for some minutes, a female baby weighing 2130 g was delivered at 11:54 pm with a pediatrician on standby. Apgar scores were 7 (0 minute), 9 (5 minutes), and 10 (10 minutes). The placenta weighed 870 g and was delivered 5 minutes later, and VCI was discovered.

Outcomes:

Her postpartum course was uncomplicated and both the patient and infant were discharged 3 days later.

Lessons:

A pregnant woman with umbilical prolapse, VCI, and a fetal vertex presentation can successfully deliver a baby through the vagina. Factors contributing to the success of the reported vaginal delivery might have been a small fetus, multipara status, and immediate management.
Exploration of Mindfulness Among Ethnic Minority Undergraduate Nursing Students
Authors: Young-Brice Amber , Thomas Dreifuerst Kristina
Published: November 2018

Background

Meeting projected needs for ethnically diverse nurses depends on a strong pipeline of diverse students within nursing programs. Colleges assume students readily navigate the university; however, this may not be the reality especially among ethnic minority students.

Purpose

The purpose was to explore the concept of mindfulness among ethnic minority nursing students. Exploring mindfulness, and a lack thereof, may provide strategies for overcoming challenges ethnic minority students experience in prelicensure nursing programs.

Methods

A qualitative study using thematic analysis of semistructured in-depth interviews was conducted with 20 ethnic minority undergraduate nursing students.

Results

Themes that emerged reveal positive associations of mindfulness and negative implications when there is a lack of mindfulness.

Conclusion

Based on the findings from this study, using consistent mindfulness techniques could positively influence coping skills for dealing with the stressors of college, resulting in overall success and retention of ethnic minority and first-generation students in a nursing program.
Early Peritoneal Dialysis and Major Adverse Events After Pediatric Cardiac Surgery: A Propensity Score Analysis*
Authors: Namachivayam Siva P. , Butt Warwick , Millar Johnny , Konstantinov Igor E. , Nguyen Cattram , d’Udekem Yves
Published: November 2018

Objectives:

Early peritoneal dialysis may have a role in modulating the inflammatory response after cardiopulmonary bypass. This study sought to test the effect of early peritoneal dialysis on major adverse events after pediatric cardiac surgery involving cardiopulmonary bypass.

Design:

In this observational study, the outcomes in infants post cardiac surgery who received early peritoneal dialysis (within 6 hr of completing cardiopulmonary bypass) were compared with those who received late peritoneal dialysis. The primary outcome was a composite of one or more of cardiac arrest, emergency chest reopening, requirement for extracorporeal membrane oxygenation, or death. Secondary outcomes included duration of mechanical ventilation, length of intensive care, and hospital stay. A propensity score methodology utilizing inverse probability of treatment weighting was used to minimize selection bias due to timing of peritoneal dialysis.

Setting:

Cardiac ICU, The Royal Children’s Hospital, Melbourne, VIC, Australia.

Patients:

From 2012 to 2015, infants who were commenced on peritoneal dialysis after cardiac surgery were included.

Measurements and Main Results:

Among 239 eligible infants, 56 (23%) were commenced on early peritoneal dialysis and 183 (77%) on late peritoneal dialysis. At 90 days, early peritoneal dialysis as compared with late peritoneal dialysis was associated with a decreased risk of primary outcome (relative risk, 0.16; 95% CI, 0.05–0.47; p < 0.001 and absolute risk difference, –18.1%; 95% CI, –25.1 to –11.1; p < 0.001). Early peritoneal dialysis was also associated with a decrease in duration of mechanical ventilation and intensive care stay. Among infants with a cardiopulmonary bypass greater than 150 minutes, early peritoneal dialysis was also associated with a survival advantage (relative risk, 0.14; 95% CI, 0.03–0.84; p = 0.03 and absolute risk difference, –7.8; 95% CI, –13.6 to –2; p = 0.008).

Conclusions:

Early peritoneal dialysis in infants post cardiac surgery is associated with a decrease in the rate of major adverse events. The role of early peritoneal dialysis warrants the conduct of randomized trials both in high and low-to-middle income countries; any beneficial effects if confirmed have the potential to strongly influence outcomes for children born with congenital heart disease.
Confronting Subconscious Bias
Authors: Dreisinger Naomi , Soorma Haresh
Published: November 2018

Physicians are only human. Upon graduating from medical school, physicians take an oath declaring veracity and fidelity toward our patients. We are told to lay aside negative feelings toward patients in exchange for integrity, truth, honor, and compassion. The idea is simple, but following through on it is quite a challenge. Pediatric emergency medicine physicians generally have rapid focused patient interactions, yet even in these brief encounters, instantaneous and subconscious reactions to difficult patients occur. Difficult patients are those who raise negative feelings within the clinician such as anxiety, frustration, guilt, and dislike. Recognition of these reactions and emotions will help physicians understand more about themselves, and assist in interacting more favorably with challenging patients. It is common for doctors to attempt to suppress their human reactions to maintain clinical objectivity, yet these reactions facilitate a better doctor-patient relationship. Allowing ourselves to yield to our emotions help the patient realize that the physician is a human being.
Reflexive Laboratory-Based Cryptococcal Antigen Screening and Preemptive Fluconazole Therapy for Cryptococcal Antigenemia in HIV-Infected Individuals With CD4 <100 Cells/µL: A Stepped-Wedge, Cluster-Randomized Trial
Authors: Meya David B. , Kiragga Agnes N. , Nalintya Elizabeth , Morawski Bozena M. , Rajasingham Radha , Park Benjamin J. , Mubiru Anthony , Kaplan Jonathan E. , Manabe Yukari C. , Boulware David R. ,   on behalf of the ORCAS study team
Published: November 2018

Background:

HIV-infected persons with cryptococcal antigenemia (CrAg) are at high risk for meningitis or death. We evaluated the effect of CrAg screening and preemptive fluconazole therapy, adjunctive to antiretroviral therapy (ART), on 6-month survival among persons with advanced HIV/AIDS.

Methods:

We enrolled HIV-infected, ART-naive participants with <100 CD4 cells/µL, in a stepped-wedge, cluster-randomized trial from July 2012 to December 2014 at 17 Ugandan clinics. Clinics participated in a prospective observational phase, followed by an interventional phase with laboratory-based, reflexive CrAg screening of residual CD4 count plasma. Asymptomatic CrAg+ participants received preemptive fluconazole therapy. We assessed 6-month survival using Cox-regression, adjusting for nadir CD4, calendar time, and stepped-wedge steps.

Results:

We included 1280 observational and 2108 interventional participants, of whom 9.3% (195/2108) were CrAg+. CD4-, time-, and stepped-wedge–adjusted analyses demonstrated no difference in survival in the observational vs the interventional arms (hazard ratio = 1.34; 95% confidence interval: 0.86 to 2.10; P = 0.20). Fewer participants initiated ART in the interventional (73%) versus the observational phase (82%, P < 0.001). When ART initiation was modeled as a time-dependent covariate or confounder, survival did not differ. However, 6-month mortality of participants with CrAg titers <1:160 and CrAg-negative patients did not differ. Patients with CrAg titers ≥1:160 had 2.6-fold higher 6-month mortality than patients with titers <1:160.

Conclusions:

We observed no overall survival benefit of the CrAg screen-and-treat intervention. However, preemptive antifungal therapy for asymptomatic cryptococcosis seemed to be effective in patients with CrAg titer <1:160. A more aggressive approach is required for persons with CrAg titer ≥1:160.
The impact of frailty on acute care general surgery patients: A systematic review
Authors: Ward Mellissa A. R. , Alenazi Abdullah , Delisle Megan , Logsetty Sarvesh
Published: November 2018

BACKGROUND

Frailty may predict negative health outcomes more accurately than chronological age alone. This review examines evidence for the impact of frailty on adverse outcomes in patients admitted with an acute care general surgery (ACS) diagnosis.

METHODS

A systematic literature search for studies reporting frailty and outcomes after admission with an ACS diagnosis was performed. We searched PubMed and SCOPUS from inception until September 2017.

RESULTS

A total of 8,668 records were screened, of which seven studies examined the relationship between frailty and outcomes in ACS patients. Frailty was associated with higher 30-day mortality patients (odds ratio, 3.04; 95% confidence interval, 2.67–3.46; p < 0.01), postoperative complications, length of stay, institutional discharge, and critical care admission.

CONCLUSIONS

There is emerging evidence that frailty is associated with worse outcomes in patients with an unplanned admission due to an ACS diagnosis. Further investigation is warranted with regard to how frailty may impact patients with an acute illness more severely.

LEVEL OF EVIDENCE

Systematic review, level III.
Impact of Affordable Care Act–related insurance expansion policies on mortality and access to post-discharge care for trauma patients: an analysis of the National Trauma Data Bank
Authors: Scott John W. , Neiman Pooja U. , Uribe-Leitz Tarsicio , Scott Kirstin W. , Zogg Cheryl K. , Salim Ali , Haider Adil H.
Published: November 2018

BACKGROUND

Uninsured trauma patients have worse outcomes and worse access to post-discharge care that is critically important for recovery after injury. Little is known regarding the impact of the insurance coverage expansion policies of the Affordable Care Act (ACA), most notably state-level Medicaid expansion, on trauma patients. In this study, we examine the national impact of these policies on payer mix, inpatient mortality, and access to post-acute care for trauma patients.

METHODS

We used the 2011–2016 National Trauma Data Bank to evaluate for changes in insurance coverage among trauma patients 18–64 years old. Our pre-/post-expansion models defined 2011–2013 as the pre-policy period, 2015–2016 as the post-policy period, and 2014 as a washout year. To evaluate for policy-associated changes in inpatient mortality and discharge disposition among the policy-eligible sample, we leveraged multivariable linear regression techniques to adjust for year-to-year variation in patient demographics, injury characteristics, and facility traits. We then examined the relationship between the magnitude of facility-level reductions in uninsured patients and access to post-acute care after policy implementation.

RESULTS

We identified 1,656,469 patients meeting inclusion criteria between 2011 and 2016. The pre-policy uninsured rate of 23.4% fell by 5.9 percentage-points after coverage expansion (p < 0.001), with a corresponding 7.5 percentage-point increase in Medicaid coverage (p < 0.001). After policy implementation, there were no significant changes in inpatient mortality. However, there was a >30% relative increase in discharge to a post-acute care facility and a similar increase in discharge with home health services (p < 0.001 for both). The greatest gains in access to post-acute services were seen among facilities with the greatest reductions in their uninsured rate (p = 0.003).

CONCLUSION

ACA-related coverage expansion policies, most notably Medicaid expansion, were associated with a >25% reduction in the uninsured rate among non-elderly adult trauma patients. Although no immediate impact on inpatient mortality was seen, insurance coverage expansion was associated with a higher proportion of patients receiving critically important post-discharge care.

LEVEL OF EVIDENCE

Epidemiological, level III.
A Randomized Controlled Trial of Naloxone for Optimization of Hypoxemia in Lung Donors After Brain Death
Authors: Dhar Rajat , Stahlschmidt Emily , Paramesh Anil , Marklin Gary
Published: November 2018

Background.

Persistent hypoxemia is the principal reason lungs from otherwise eligible brain dead (BD) organ donors are not transplanted. Experimental models and retrospective studies have suggested that naloxone attenuates neurogenic pulmonary edema and reverses hypoxemia after brain death. We undertook a multisite, randomized, placebo-controlled trial to evaluate whether naloxone is able to improve oxygenation in BD donors with hypoxemia.

Methods.

BD organ donors at 4 organ procurement organizations were randomized in a blinded manner to naloxone 8 mg or saline placebo if lung were being considered for allocation but exhibited hypoxemia (partial pressure of oxygen in arterial blood to fraction of inspired oxygen ratio [PFR] below 300 mm Hg). The primary outcome was change in PFR from baseline to final arterial blood gas. Secondary outcomes included early improvement in PFR and proportion of lungs transplanted.

Results.

A total of 199 lung-eligible BD donors were randomized to naloxone (n = 98) or placebo (n = 101). Groups were comparable at baseline. Both groups exhibited similar improvements in oxygenation (median improvement in PFR of 81 with naloxone versus 80 with saline, P = 0.68), with 37 (39%) versus 38 (40%) exhibiting reversal of hypoxemia. There was no difference in the rate of lungs transplanted (19% in both groups, P = 0.97) although it was significantly higher in those with reversal of hypoxemia (32/69 versus 2/111, P < 0.001).

Conclusions.

Naloxone does not improve oxygenation more than placebo in hypoxemic organ donors. However, reversal of hypoxemia was a powerful predictor of lung utilization regardless of drug therapy. Further organ procurement organization–led research is needed to assess optimal interventions to improve oxygenation in BD donors with hypoxemia.
Investigating causal relationships between sleep traits and risk of breast cancer: a Mendelian randomization study
Authors: Richmond Rebecca C. , Anderson Emma L. , Dashti Hassan S. , Jones Samuel E. , Lane Jacqueline M. , Strand Linn Beate , Brumpton Ben , Rutter Martin , Wood Andrew R. , Relton Caroline L. , Munafò Marcus , Frayling Timothy M. , Martin Richard M. , Saxena Richa , Weedon Michael N. , Lawlor Debbie A. , Davey Smith George
Published: November 2018

Objective

To examine whether sleep traits have a causal effect on risk of breast cancer.

Design

Multivariable regression, one- and two-sample Mendelian randomization.

Setting

The UK Biobank prospective cohort study and the Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.

Participants

156,848 women in the multivariable regression and one-sample Mendelian randomization analysis in UK Biobank (7,784 with a breast cancer diagnosis) and 122,977 breast cancer cases and 105,974 controls from BCAC in the two-sample Mendelian randomization analysis.

Exposures

Self-reported chronotype (morning/evening preference), insomnia symptoms and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits.

Main outcome measures

Breast cancer (prevalent and incident cases in UK Biobank, prevalent cases only in BCAC).

Results

In multivariable regression analysis using data on breast cancer incidence in UK Biobank, morning preference was inversely associated with breast cancer (HR 0.95, 95% CI 0.93, 0.98 per category increase) while there was little evidence for an association with sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated sleep duration and 57 SNPs associated with insomnia symptoms, one-sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (HR 0.85, 95% 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two-sample MR using data from BCAC supported findings for a protective effect of morning preference (OR 0.88, 95% CI 0.82, 0.93 per category increase) and adverse effect of increased sleep duration (OR 1.19, 95% CI 1.02, 1.39 per hour increase) on breast cancer (both estrogen receptor positive and negative), while there was inconsistent evidence for insomnia symptoms. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy.

Conclusions

We found consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of sleep duration on breast cancer risk.
In Silico Analysis of Non Synonymous Single Nucleotide Polymorphisms (nsSNPs) of SMPX Gene in Hearing Impairment
Authors: Arifuzzaman Md. , Mitra Sarmistha , Hamza Amir , Das Raju , Absar Nurul , Dash Raju
Published: November 2018

Background

Mutations in SMPX gene can disrupt the normal activity of the SMPX protein which is involved in hearing process.

Objective

In this study, deleterious non-synonymous single nucleotide polymorphisms were isolated from the neutral variants by using several bioinformatics tools.

Method

Firstly, dbSNP database hosted by NCBI was used to retrieve the SNPs of SMPX gene, secondly, SIFT was used primarily to screen the damaging SNPs. Further, for validation PROVEAN, PredictSNP and PolyPhen 2 were used. I-Mutant 3 was utilized to analyze the protein stability change and MutPred predicted the molecular mechanism of protein stability change. Finally evolutionary conservation was done to study their conservancy by using ConSurf server.

Results

A total of 26 missense (0.6517%) and 3 nonsense variants (0.075%) were retrieved and among them 4 mutations were found deleterious by all the tools of this experiment and are also highly conserved according to ConSurf server. rs772775896, rs759552778, rs200892029 and rs1016314772 are the reference IDs of deleterious mutations where the substitutions are S71L, N19D, A29T and K54N. Loss of Ubiquitination, loss of methylation, loss of glycosylation, and loss of MoRF binding motifs are the root causes of protein stability change.

Conclusion

This is the first study regarding nsSNPs of SMPX gene where the most damaging SNPs were screened that are associated with the SMPX gene and can be used for further research to study their effect on protein structure and function, their dynamic behavior and how they actually affect protein’s flexibility.
Nitric oxide is important for sensing and survival under hypoxia in Arabidopsis
Authors: Wany Aakanksha , Gupta Alok Kumar , Brotman Yariv , Pandey Sonika , Vishwakarma Abhay Pratap , Kumari Aprajita , Singh Pooja , Pathak Pradeep K , Igamberdiev Abir U. , Gupta Kapuganti Jagadis
Published: November 2018

Nitric oxide (NO) is a free radical molecule that plays an important role in hypoxic stress. We studied the impact of hypoxia-induced NO production on the expression of genes and production of metabolites involved in carbon, oxygen sensing, nitrogen, and antioxidant metabolism using wild type (WT), non-symbiotic haemoglobin-overexpressing (Hb+) and nitrate reductase double mutant (nia1,2) of Arabidopsis. Futher application of NO scavenger cPTIO was used to confirm NO role. We found that imposing hypoxia leads to the increaseof NO and reactive oxygen species (ROS) levels in WT, while the reduced levels of NO and higher levels of ROS were observed in roots of Hb+andnia1,2mutant. Expression of the genes encoding oxygen sensing and the enzymes involved in fermentative pathways, their activities and metabolite levels were highly induced in WT suggesting that NO plays a role in the induction of fermentation. Several genes and metabolites involved in the TCA cycle were also induced in WT in comparison to Hb+andniamutant line suggesting that NO can accelerate TCA cycle to regenerate reducing equivalents under hypoxia. Interestingly, we found that the genes and metabolites involved in the ascorbate-glutathione cycle were modulated by NO under hypoxia. The alternative oxidasegene (AOX1A) was induced under hypoxia in WTdue to increased levels of NO rather than ROS. Futher, we found that NO improves plant survival. Overall these findings suggest that NO is a major player in plant survival under hypoxia by modulating gene expression and metabolite levels of carbon, nitrogen, oxygen sensing and antioxidant metabolism.

Highlight

Hypoxia-induced nitric oxide plays a central role in activation of genes and metabolites involved in fermentation, TCA cycle, nitrogen and antioxidant metabolism
Individualised MRI training for paediatric neuroimaging in autism spectrum disorders: A child-focused approach
Authors: Kiat Pua Emmanuel Peng , Barton Sarah , Williams Katrina , Craig Jeffrey M , Seal Marc L
Published: November 2018

Magnetic Resonance Imaging (MRI) in paediatric cohorts is often complicated by reluctance to enter the scanner and head motion-related imaging artefacts. The MRI scanner environment is highly unusual and may distress younger cohorts, especially in children with sensory sensitivity and separation anxiety. The issue is particularly challenging in children with Autism Spectrum Disorders (ASD), where delivery of instructions for novel task demands in an unfamiliar setting may be limited or less effective due to communication disorder or intellectual disability. These issues together often give rise to excessive head motion that can significantly reduce the quality of images acquired, or render data unusable. Here we report an individualised MRI training procedure that enables young children with ASD to better tolerate the MRI scanner environment based on a child-focused approach and an individualised familiarisation strategy. The training procedure was implemented in a locally recruited study of monozygotic twins (n=12; 6 twin pairs; age range 7.1 to 12.85 years) concordant or discordant for ASD. MRI image quality indices were better or comparable to images acquired from an independent multi-centre ASD cohort. The success of these findings is promising and may be useful to improve the quality of paediatric neuroimaging in similar clinical populations.
High resolution protein-protein interaction mapping using all-versus-all sequencing (AVA-seq)
Authors: Andrews Simeon S. , Schaefer-Ramadan Stephanie , Al-Thani Nayra M. , Ahmed Ikhlak , Mohamoud Yasmin A. , Malek Joel A.
Published: November 2018

Two-hybrid systems test for protein-protein interactions and can provide important information for genes with unknown function. Despite their success, two-hybrid systems have remained mostly untouched by improvements from next-generation DNA sequencing. Here we present a method for all-versus-all protein interaction mapping (AVA-seq) that utilizes next-generation sequencing to remove multiple bottlenecks of the two-hybrid process. The method allows for high resolution protein-protein interaction mapping of a small set of proteins, or the potential for lower-resolution mapping of entire proteomes. Features of the system include open-reading frame selection to improve efficiency, high bacterial transformation efficiency, a convergent fusion vector to allow paired-end sequencing of interactors, and the use of protein fragments rather than full-length genes to better resolve specific protein contact points. We demonstrate the system’s strengths and limitations on a set of proteins known to interact in humans and provide a framework for future large-scale projects.
Pectin digestion in herbivorous beetles: Impact of pseudoenzymes exceeds that of their active counterparts
Authors: Kirsch Roy , Kunert Grit , Vogel Heiko , Pauchet Yannick
Published: November 2018

Many protein families harbor pseudoenzymes that have lost the catalytic function of their enzymatically active counterparts. Assigning alternative function and importance to these proteins is challenging [1]. Because the evolution towards pseudoenzymes is driven by gene duplication, they often accumulate in multigene families. Plant cell wall-degrading enzymes (PCWDEs) are prominent examples of expanded gene families. The pectolytic glycoside hydrolase family 28 (GH28) allows herbivorous insects to break down the PCW polysaccharide pectin. GH28 in the Phytophaga clade of beetles contains many active enzymes but also many inactive counterparts. Using functional characterization, gene silencing, global transcriptome analyses and recordings of life history traits, we found that not only catalytically active but also inactive GH28 proteins are part of the same pectin-digesting pathway. The robustness and plasticity of this pathway and thus its importance for the beetle is supported by extremely high steady-state expression levels and counter-regulatory mechanisms. Unexpectedly, the impact of pseudoenzymes on the pectin-digesting pathway in Phytophaga beetles exceeds even the influence of their active counterparts, such as a lowered efficiency of food-to-energy conversion and a prolongation of the developmental period.
Inferring biochemical reactions and metabolite structures to cope with metabolic pathway drift
Authors: Belcour Arnaud , Girard Jean , Aite Méziane , Delage Ludovic , Trottier Camille , Marteau Charlotte , Leroux Cédric , Dittami Simon M. , Sauleau Pierre , Corre Erwan , Nicolas Jacques , Boyen Catherine , Leblanc Catherine , Collén Jonas , Siegel Anne , Markov Gabriel V.
Published: November 2018

Inferring genome-scale metabolic networks in emerging model organisms is challenging because of incomplete biochemical knowledge and incomplete conservation of biochemical pathways during evolution. This limits the possibility to automatically transfer knowledge from well-established model organisms. Therefore, specific bioinformatic tools are necessary to infer new biochemical reactions and new metabolic structures that can be checked experimentally. Using an integrative approach combining both genomic and metabolomic data in the red algal modelChondrus crispus, we show that, even metabolic pathways considered as conserved, like sterol or mycosporine-like amino acids (MAA) synthesis pathways, undergo substantial turnover. This phenomenon, which we formally define as “metabolic pathway drift”, is consistent with findings from other areas of evolutionary biology, indicating that a given phenotype can be conserved even if the underlying molecular mechanisms are changing. We present a proof of concept with a new methodological approach to formalize the logical reasoning necessary to infer new reactions and new molecular structures, based on previous biochemical knowledge. We use this approach to infer previously unknown reactions in the sterol and MAA pathways.

Author summary

Genome-scale metabolic models describe our current understanding of all metabolic pathways occuring in a given organism. For emerging model species, where few biochemical data are available about really occurring enzymatic activities, such metabolic models are mainly based on transferring knowledge from other more studied species, based on the assumption that the same genes have the same function in the compared species. However, integration of metabolomic data into genome-scale metabolic models leads to situations where gaps in pathways cannot be filled by known enzymatic reactions from existing databases. This is due to structural variation in metabolic pathways accross evolutionary time. In such cases, it is necessary to use complementary approaches to infer new reactions and new metabolic intermediates using logical reasoning, based on available partial biochemical knowledge. Here we present a proof of concept that this is feasible and leads to hypotheses that are precise enough to be a starting point for new experimental work.
The shape of a defense-growth trade-off governs seasonal trait dynamics in natural phytoplankton
Authors: Ehrlich Elias , Kath Nadja J. , Gaedke Ursula
Published: November 2018

Functional trait compositions of communities can adapt to altered environmental conditions ensuring community persistence. Theory predicts that the shape of trade-offs between traits crucially affects these trait dynamics, but its empirical verification from the field is missing. Here, we show how the shape of a defense-growth trade-off governs seasonal trait dynamics of a natural community, using high-frequency, long-term measurements of phytoplankton from Lake Constance. As expected from the lab-derived concave trade-off curve, we observed an alternating dominance of several fast-growing species with intermediate defense levels and gradual changes of the biomass-trait distribution due to seasonally changing grazing pressure. By combining data and modelling, we obtain mechanistic insights on the underlying fitness landscape, and show that low fitness differences can maintain trait variation along the trade-off curve. We provide firm evidence for a frequently assumed trade-off and conclude that quantifying its shape allows to understand environmentally driven trait changes within communities.
Dynamic Electrical Stimulation of Sites in Visual Cortex Produces Form Vision in Sighted and Blind Humans
Authors: Beauchamp Michael S. , Bosking William , Sun Ping , Foster Brett , Niketeghad Soroush , Pouratian Nader , Yoshor Daniel
Published: November 2018

Visual cortical prosthetics (VCPs) offer the promise of restoring sight to blind patients. Electrical stimulation of a single site in visual cortex can reliably produce a percept of a spot of light in a fixed visual field location, known as a phosphene. Researchers developing VCPs have assumed that multiple phosphenes produced by concurrent stimulation of multiple sites in visual cortex can combine to form a coherent form, like pixels in a visual display. However, existing data do not support this assumption. Therefore, we developed a novel stimulation paradigm for VCPs termeddynamic current steeringin which the visual form to be conveyed is traced on the surface of visual cortex by electrically stimulating electrodes in a dynamic sequence. When tested in sighted and blind subjects, this method of stimulating visual cortex allowed for the immediate recognition of a variety of letter shapes without training and with high accuracy.

One Sentence Summary

Stimulating human visual cortex using dynamic patterns of activity allows both blind and sighted patients to perceive visual percepts of useful forms.
PSL-Recommender: Protein Subcellular Localization Prediction using Recommender System
Authors: Jamali Ruhollah , Eslahchi Changiz , Jahangiri-Tazehkand Soheil
Published: November 2018

Identifying a protein’s subcellular location is of great interest for understanding its function and behavior within the cell. In the last decade, many computational approaches have been proposed as a surrogate for expensive and inefficient wet-lab methods that are used for protein subcellular localization. Yet, there is still much room for improving the prediction accuracy of these methods.

PSL-Recommender (Protein subcellular location recommender) is a method that employs neighborhood regularized logistic matrix factorization to build a recommender system for protein subcellular localization. The effectiveness of PSL-Recommender method is benchmarked on one human and three animals datasets. The results indicate that the PSL-Recommender significantly outperforms state-of-the-art methods, improving the previous best method up to 31% in F1 – mean, up to 28% in ACC, and up to 47% in AVG. The source of datasets and codes are available at:https://github.com/RJamali/PSL-Recommender
Single cell analysis reveals dynamics of transposable element transcription following epigenetic de-repression
Authors: Brocks David , Chomsky Elad , Mukamel Zohar , Lifshitz Aviezer , Tanay Amos
Published: November 2018

Spontaneous or pharmacological loss of epigenetic repression exposes thousands of promoters encoded in transposable elements (TEs) for pervasive transcriptional activation. How TE responses differ between epigenetically relaxed cancer cells and what factors govern such variation remains however largely unknown. By quantifying TE transcription initiation at single cell and locus resolution in epigenetically targeted cancer cells, we characterize specific groups of co-regulated loci that drive over ten-fold variation in TE load per single cell. Such variable activity patterns are largely linked to cell cycle stages, stress response signatures, and immune pathways. Furthermore, cells with high levels of specific transcription factors show increased TE expression, while within such cells, multi-copy families are differentially regulated in response to local sequence divergence of binding sites and the locus’ repressive or active chromosomal contexts. Our data thereby implicates the regulation of potent promoters within TEs as an underestimated source of transcriptional heterogeneity following epigenetic therapy.
A chemogenetic approach for optical monitoring of voltage in neurons
Authors: Sundukova Mayya , Prifti Efthymia , Bucci Annalisa , Kirillova Kseniia , Serrao Joana , Reymond Luc , Umebayashi Miwa , Hovius Ruud , Riezman Howard , Johnsson Kai , Heppenstall Paul A.
Published: November 2018

Optical monitoring of neuronal voltage using fluorescent indicators is a powerful approach for interrogation of the cellular and molecular logic of the nervous system. Here we describe a Semisynthetic Tethered Voltage Indicator (STeVI1) based upon Nile Red that displays voltage sensitivity when genetically targeted to neuronal membranes. This environmentally sensitive probe allows for wash-free imaging and faithfully detects supra- and subthreshold activity in neurons.
Convergence of virulence and multidrug resistance in a single plasmid vector in multidrug-resistant Klebsiella pneumoniae ST15
Authors: Lam Margaret M. C. , Wyres Kelly L. , Wick Ryan R. , Judd Louise M. , Fostervold Aasmund , Holt Kathryn E. , Löhr Iren Høyland
Published: November 2018

SYNOPSIS

Background

Multidrug resistance (MDR) and hypervirulence (hv) are typically observed in separate Klebsiella pneumoniae populations. However, convergent strains with both properties have been documented and potentially pose a high risk to public health in the form of invasive infections with limited treatment options.

Objectives

To characterize the genetic determinants of virulence and antimicrobial resistance (AMR) in two ESBL-producing K. pneumoniae isolates belonging to the international MDR clone ST15.

Methods

The complete genome sequences of both isolates, including their plasmids, were resolved using Illumina and Oxford Nanopore sequencing.

Results

Both isolates carried large mosaic plasmids in which AMR and virulence loci have converged within the same vector. These closely related mosaic hv-MDR plasmids include sequences typical of the K. pneumoniae virulence plasmid 1 (KpVP-1; including aerobactin synthesis locus iuc) fused with sequences typical of IncFIIK conjugative AMR plasmids. One hv-MDR plasmid carried three MDR elements encoding the ESBL gene blaCTX-M-15 and eight other AMR genes (blaTEM, aac3’-IIa, aph3’-Ia, dfrA1, satA2, blaSHV, sul1, aadA1). The other carried remnants of these elements encoding blaTEM and aac3’-IIa, and blaCTX-M-15 was located in a second plasmid in this isolate. The two isolates originated from patients hospitalized in Norway but have epidemiological and genomic links to Romania.

Conclusions

The presence of both virulence and AMR determinants on a single vector enables simultaneous transfer in a single event and potentially rapid emergence of hv-MDR K. pneumoniae clones. This highlights the importance of monitoring for such convergence events with stringent genomic surveillance.
AnnoTree: visualization and exploration of a functionally annotated microbial tree of life
Authors: Mendler Kerrin , Chen Han , Parks Donovan H. , Hug Laura A. , Doxey Andrew C.
Published: November 2018

Bacterial genomics has revolutionized our understanding of the microbial tree of life; however, mapping and visualizing the distribution of functional traits across bacteria remains a challenge. Here, we introduce AnnoTree - an interactive, functionally annotated bacterial tree of life that integrates taxonomic, phylogenetic, and functional annotation data from nearly 24,000 bacterial genomes. AnnoTree enables visualization of millions of precomputed genome annotations across the bacterial phylogeny, thereby allowing users to explore gene distributions as well as patterns of gene gain and loss across bacteria. Using AnnoTree, we examined the phylogenomic distributions of 28,311 gene/protein families, and measured their phylogenetic conservation, patchiness, and lineage-specificity. Our analyses revealed widespread phylogenetic patchiness among bacterial gene families, reflecting the dynamic evolution of prokaryotic genomes. Genes involved in phage infection/defense, mobile elements, and antibiotic resistance dominated the list of most patchy traits, as well as numerous intriguing metabolic enzymes that appear to have undergone frequent horizontal transfer. We anticipate that AnnoTree will be a valuable resource for exploring gene histories across bacteria, and will act as a catalyst for biological and evolutionary hypothesis generation.
Assessment of bilateral knee pain from MR imaging using deep neural networks
Authors: Chang Gary H. , Felson David T. , Qiu Shangran , Capellini Terence D. , Kolachalama Vijaya B.
Published: November 2018

Background and objective

It remains difficult to characterize pain in knee joints with osteoarthritis solely by radiographic findings. We sought to understand how advanced machine learning methods such as deep neural networks can be used to analyze raw MRI scans and predict bilateral knee pain, independent of other risk factors.

Methods

We developed a deep learning framework to associate information from MRI slices taken from the left and right knees of subjects from the Osteoarthritis Initiative with bilateral knee pain. Model training was performed by first extracting features from two-dimensional (2D) sagittal intermediate-weighted turbo spin echo slices. The extracted features from all the 2D slices were subsequently combined to directly associate using a fused deep neural network with the output of interest as a binary classification problem.

Results

The deep learning model resulted in predicting bilateral knee pain on test data with 70.1% mean accuracy, 51.3% mean sensitivity, and 81.6% mean specificity. Systematic analysis of the predictions on the test data revealed that the model performance was consistent across subjects of different Kellgren-Lawrence grades.

Conclusion

The study demonstrates a proof of principle that a machine learning approach can be applied to associate MR images with bilateral knee pain.

SIGNIFICANCE AND INNOVATION

Knee pain is typically considered as an early indicator of osteoarthritis (OA) risk. Emerging evidence suggests that MRI changes are linked to pre-clinical OA, thus underscoring the need for building image-based models to predict knee pain. We leveraged a state-of-the-art machine learning approach to associate raw MR images with bilateral knee pain, independent of other risk factors.
NEPRE: a Scoring Function for Protein Structures based on Neighbourhood Preference
Authors: Liu Siyuan , Xiang Xilun , Liu Haiguang
Published: November 2018

Protein structure prediction relies on two major components, a method to generate good models that are close to the native structure and a scoring function that can select the good models. Based on the statistics from known structures in the protein data bank, a statistical energy function is derived to reflect the amino acid neighbourhood preferences. The neighbourhood of one amino acid is defined by its contacting residues, and the energy function is determined by the neighbhoring residue types and relative positions. A scoring algorithm, Nepre, has been implemented and its performance was tested with several decoy sets. The results show that the Nepre program can be applied in model ranking to improve the success rate in structure predictions.