bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial intelligence–derived 3-Way Concentration-dependent Antagonism of Gatifloxacin, Pyrazinamide, and Rifampicin During Treatment of Pulmonary Tuberculosis
Authors: Pasipanodya Jotam G , Smythe Wynand , Merle Corinne S , Olliaro Piero L , Deshpande Devyani , Magombedze Gesham , McIlleron Helen , Gumbo Tawanda
Published: July 2018

Background

In the experimental arm of the OFLOTUB trial, gatifloxacin replaced ethambutol in the standard 4-month regimen for drug-susceptible pulmonary tuberculosis. The study included a nested pharmacokinetic (PK) study. We sought to determine if PK variability played a role in patient outcomes.

Methods

Patients recruited in the trial were followed for 24 months, and relapse ascertained using spoligotyping. Blood was drawn for drug concentrations on 2 separate days during the first 2 months of therapy, and compartmental PK analyses was performed. Failure to attain sustained sputum culture conversion at the end of treatment, relapse, or death during follow-up defined therapy failure. In addition to standard statistical analyses, we utilized an ensemble of machine-learning methods to identify patterns and predictors of therapy failure from among 27 clinical and laboratory features.

Results

Of 126 patients, 95 (75%) had favorable outcomes and 19 (15%) failed therapy, relapsed, or died. Pyrazinamide and rifampicin peak concentrations and area under the concentration-time curves (AUCs) were ranked higher (more important) than gatifloxacin AUCs. The distribution of individual drug concentrations and their ranking varied significantly between South African and West African trial sites; however, drug concentrations still accounted for 31% and 75% of variance of outcomes, respectively. We identified a 3-way antagonistic interaction of pyrazinamide, gatifloxacin, and rifampicin concentrations. These negative interactions disappeared if rifampicin peak concentration was above 7 mg/L.

Conclusions

Concentration-dependent antagonism contributed to death, relapse, and therapy failure but was abrogated by high rifampicin concentrations. Therefore, increasing both rifampin and gatifloxacin doses could improve outcomes.

Clinical Trials Registration

NCT002216385.
The association of calcium oxalate deposition in kidney allografts with graft and patient survival
Authors: Palsson Ragnar , Chandraker Anil K , Curhan Gary C , Rennke Helmut G , McMahon Gearoid M , Waikar Sushrut S
Published: July 2018

Background

Whether calcium oxalate (CaOx) deposition in kidney allografts following transplantation (Tx) adversely affects patient outcomes is uncertain, as are its associated risk factors.

Methods

We performed a retrospective cohort study of patients who had kidney allograft biopsies performed within 3 months of Tx at Brigham and Women’s Hospital and examined the association of CaOx deposition with the composite outcome of death or graft failure within 5 years.

Results

Biopsies from 67 of 346 patients (19.4%) had CaOx deposition. In a multivariable logistic regression model, higher serum creatinine [odds ratio (OR) = 1.28 per mg/dL, 95% confidence interval (CI) 1.15–1.43], longer time on dialysis (OR = 1.11 per additional year, 95% CI 1.01–1.23) and diabetes (OR = 2.26, 95% CI 1.09–4.66) were found to be independently associated with CaOx deposition. CaOx deposition was strongly associated with delayed graft function (DGF; OR = 11.31, 95% CI 5.97–21.40), and with increased hazard of the composite outcome after adjusting for black recipient race, donor type, time on dialysis before Tx, diabetes and borderline or acute rejection (hazard ratio 1.90, 95% CI 1.13–3.20).

Conclusions

CaOx deposition is common in allografts with poor function and portends worse outcomes up to 5 years after Tx. The extent to which CaOx deposition may contribute to versus result from DGF, however, cannot be determined based on our retrospective and observational data. Future studies should examine whether reducing plasma and urine oxalate prevents CaOx deposition in the newly transplanted kidney and whether this has an effect on clinical outcomes.
Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Evaluation and Treatment of Patients with Thoracolumbar Spine Trauma: Executive Summary
Authors: O’Toole John E , Kaiser Michael G , Anderson Paul A , Arnold Paul M , Chi John H , Dailey Andrew T , Dhall Sanjay S , Eichholz Kurt M , Harrop James S , Hoh Daniel J , Qureshi Sheeraz , Rabb Craig H , Raksin P B
Published: July 2018

BACKGROUND

The thoracic and lumbar (“thoracolumbar”) spine are the most commonly injured region of the spine in blunt trauma. Trauma of the thoracolumbar spine is frequently associated with spinal cord injury and other visceral and bony injuries. Prolonged pain and disability after thoracolumbar trauma present a significant burden on patients and society.

OBJECTIVE

To formulate evidence-based clinical practice recommendations for the care of patients with injuries to the thoracolumbar spine.

METHODS

A systematic review of the literature was performed using the National Library of Medicine PubMed database and the Cochrane Library for studies relevant to thoracolumbar spinal injuries based on specific clinically oriented questions. Relevant publications were selected for review.

RESULTS

For all of the questions posed, the literature search yielded a total of 6561 abstracts. The task force selected 804 articles for full text review, and 78 were selected for inclusion in this overall systematic review.

CONCLUSION

The available evidence for the evaluation and treatment of patients with thoracolumbar spine injuries demonstrates considerable heterogeneity and highly variable degrees of quality. However, the workgroup was able to formulate a number of key recommendations to guide clinical practice. Further research is needed to counter the relative paucity of evidence that specifically pertains to patients with only thoracolumbar spine injuries.

The full version of the guideline can be reviewed at: https://www.cns.org/guideline-chapters/congress-neurological-surgeons-systematic-review-evidence-based-guidelines/chapter_1.
Effects of the Mixed Parallel Electoral System in Lithuania: The Worst of All Worlds?
Authors: Jastramskis Mažvydas
Published: July 2018

This article analyses the political effects of the mixed parallel electoral system in Lithuania. According to the ‘best of both worlds’ logic, mixed systems could combine advantages from both the majoritarian and proportional formulas. However, counterarguments were also presented in the literature, pointing to the possibility of the ‘worst of both worlds’. According to presented analysis of Lithuanian parliamentary elections between 1992 and 2016, the pessimistic scenario is expected when a mixed parallel electoral system is used in a new democracy with a weakly institutionalised party system and high volatility. Lithuania’s mixed parallel system produces relatively disproportional election results. However, it also facilitates the fragmentation of party system. Moreover, the effects in a concrete election are hardly predictable, especially the seat bonus of election winner. Evidence in the article points to a conclusion that mixed parallel electoral systems could contribute to the ‘worst of all worlds’ and new democracies should avoid them.
Physician assistants in urgent care
Authors: Ritsema Tamara S. , Cawley James F. , Smith Noël
Published: July 2018

Objective:

To describe the characteristics of physician assistants (PAs) who practice urgent care.

Methods:

Data from national surveys conducted by the American Academy of PAs (AAPA) between 1998 and 2016 were analyzed, comparing PAs who practice in urgent care, emergency medicine, and all other specialties.

Results:

The percentage of PAs who work in an urgent care setting has nearly doubled in the last 10 years. PAs who work in urgent care see more patients and perform more minor surgical procedures than those in emergency medicine. They are less likely to be newly graduated PAs than those in emergency medicine. PAs in urgent care are less likely than other PAs to consult a physician about their patients in real time.

Conclusion:

The number of PAs practicing urgent care is increasing. More research is needed to further characterize PA practice in this specialty.
Do nonsteroidal anti-inflammatory drugs impair tissue healing?
Authors: Fowler Curtis
Published: July 2018

Nonsteroidal anti-inflammatory drugs (NSAIDs) commonly are used by providers and patients to treat acute injuries. However, evidence suggests that they may interfere with healing in musculoskeletal injuries. The associated cardiac, renal, and gastrointestinal complications associated with NSAIDs are well known. This article examines the potentially negative effects of NSAIDs when they are used to treat acute musculoskeletal injuries.
Closed Borders, Closed Hearts
Authors: Kennedy Maureen Shawn
Published: July 2018

The shameful treatment of immigrants needs our collective outcry.
Suicide Among Nurses
Authors: Sofer Dalia
Published: July 2018

Poorly documented and unacknowledged.
Higher Than Optimal Nurse Workloads Increase the Odds of Patient Mortality
Authors: Zolot Joan
Published: July 2018

When workloads dropped below the assumed optimal levels, patient outcomes improved.
New Approved Use for Blinatumomab
Authors: Aschenbrenner Diane S.
Published: July 2018

Blinatumomab (Blincyto) is now approved for the treatment of adults and children with B-cell precursor acute lymphoblastic leukemia who are in remission but still have minimal residual disease.

Close adherence to the directions for reconstitution and administration of blinatumomab is required.
New Warning for Lamotrigine
Authors: Aschenbrenner, Diane S.
Published: July 2018

Lamotrigine (Lamictal) now carries a warning stating that the drug can cause hemophagocytic lymphohistiocytosis, a rare immune disorder.

Nurses should teach patients starting lamotrigine therapy about the signs and symptoms of this rare immune disorder, and those who present with these signs and symptoms should be evaluated for it.
Retired Nurse Volunteers
Authors: Elpern Ellen , Disch Joanne M.
Published: July 2018

Given the looming shortage of RNs, a viable option for hospitals to consider in optimizing available resources is the retired nurse volunteer. This article describes the benefits of using retired nurses to complement existing hospital staff and offers recommendations for setting up a program to effectively use these volunteers in the hospital setting.
Overtime Negatively Affects Nurses’ Collaboration with Coworkers
Authors: Rosenberg Karen , Mechatie Elizabeth
Published: July 2018

According to this study:

Working overtime has a negative effect on nurses’ collaboration with physicians and other nurses.
The Quandary of Scheduling Vacation Time for Nurses
Authors: Paradisi Julianna
Published: July 2018

Updated several times a week with posts by a wide variety of authors, AJN*s blog Off the Charts allows us to provide more timely—and often more personal—perspectives on professional, policy, and clinical issues. Best of the Blog will be a regular column to draw the attention of AJN readers to posts we think deserve a wider audience. To read more, please visit: www.ajnoffthecharts.com.
Cataract Surgery in Patients with Age-Related Macular Degeneration
Authors: Stern Cindy
Published: July 2018

Editor's note: This is a summary of a nursing care–related systematic review from the Cochrane Library. For more information, see http://nursingcare.cochrane.org.
Cardiovascular Effects of Chemotherapy Used in the Treatment of Breast Cancers
Authors: Rozner Raquel N. , Frishman William H.
Published: July 2018

Attempts to carry out clinical trials to improve the treatment of breast cancers, including chemotherapy and targeted oncologic therapies, often exclude women with baseline cardiovascular compromise, such as low ejection fraction or arrhythmia. Therefore, despite concrete evidence of cardiotoxicity from a select number of chemotherapeutic agents, it has been difficult to better characterize the progression of cardiac dysfunction in women with preexisting cardiac conditions who receive chemotherapy. Women who have impaired cardiac function should be included in future clinical trials, or at least placed in separate trials with careful monitoring, to better assess this high-risk population. This article will discuss the epidemiology, mechanisms, diagnostic methods, and management of cardiotoxicity from systemic chemotherapy used to treat breast cancer.
Association Between Nonalcoholic Fatty Liver Disease and Intraocular Pressure in Korean Adults
Authors: Kwon Yu-Jin , Kim Ji-Hye , Jung Dong-Hyuk
Published: July 2018

Purpose:

Elevated intraocular pressure (IOP) is an important modifiable risk factor predicting glaucoma progression. Recent studies have demonstrated that metabolic risk factors influence IOP. Nonalcoholic fatty liver (NAFLD) is an emerging chronic liver disease that is closely associated with metabolic syndrome, obesity, and type 2 diabetes. Therefore, we investigated the relationship between NAFLD and intraocular pressure in Korean adults.

Patients and Methods:

This retrospective cross-sectional study analyzed a total of 7681 participants who visited a local health promotion center. NAFLD was defined via ultrasonography and patients were classified into 3 groups based on severity: normal, mild, and moderate to severe. We conducted multiple logistic regression analysis to examine the relationship between NAFLD and high IOP. We additionally performed multiple linear regression analysis to investigate the independent association between NAFLD and mean IOP.

Results:

Mean IOP levels significantly and linearly increased with increasing NAFLD grades. Compared with normal, the odds ratio and 95% confidence intervals for high IOP were 1.09 (0.96-1.24) for mild NAFLD and 1.28 (1.12-1.48) for moderate to severe NAFLD after adjusting for confounding factors. NAFLD severity was noticed as an independent factor associated with mean IOP levels using stepwise and enter methods for multiple linear regression analyses.

Conclusions:

NAFLD severity was associated with high IOP (>15 mm Hg) in Korean adults in a dose-dependent manner.
FAB LMB 96 Regimen for Newly Diagnosed Burkitt Lymphoma in Children: Single-center Experience
Authors: Aydin Burca , Akyuz Canan , Kalkan Neslihan , Kurucu Nilgun , Varan Ali , Yalcin Bilgehan , Kutluk Tezer
Published: July 2018

Background/Objectives:

The outcome of Burkitt lymphoma has improved by over 90%. In this study, demographic characteristics and outcomes of 57 patients with Burkitt lymphoma treated with FAB LMB 96 regimen are presented.

Materials and Methods:

Standard intensity arms were selected for all risk groups. Clinical characteristics, response to treatment, and outcome were evaluated.

Results:

The median age of 48 boys and 9 girls was 8.2 years. There were 2 (3%), 41 (72%), and 14 (25%) patients in the low, intermediate, and high-risk groups, respectively. Patients were followed-up for a median of 50 months. The 5-year overall survival and event-free survival rates for the study group were 90.8% and 87.4%, respectively. Two patients in the low-risk group are still alive without evidence of disease for 17 and 57 months. The 5-year overall survival rates were 95% and 78% for intermediate and high-risk patients, and the 5-year event-free survival rates were 93% and 62%, respectively. At the end of induction, 58% of patients had complete response, and 42% (n=24) had residual tumors. A total of 16 of 24 patient biopsies showed no viable tumors.

Conclusions:

Our results confirm the previously published survival results of FAB LMB 96. The regimen is an effective regimen for mature B-cell non-Hodgkin lymphoma without radiotherapy or surgery even in central nervous system–positive patients. The most important prognostic factor is the complete response after induction chemotherapy. However, residual tumor at the end of consolidation might not always be a sign for unresponsive tumor. Tumoral residue should be radiologically well evaluated and biopsied if possible for viability before intensifying treatment.
Aberrant Nuclear Localization of aPKCλ/ι is Associated With Poorer Prognosis in Uterine Cervical Cancer
Authors: Tokinaga-Uchiyama Aya , Mizushima Taichi , Akimoto Kazunori , Nagashima Yoji , Sasaki Kazunori , Nakaya Masa-aki , Ohashi Kenichi , Kubota Kazumi , Maruyama Yasuyo , Kato Hisamori , Hirahara Fumiki , Miyagi Etsuko , Ohno Shigeo , Asai-Sato Mikiko
Published: July 2018

We previously reported that aberrant expression of atypical protein kinase C λ/ι (aPKCλ/ι) in low-grade squamous intraepithelial uterine cervix lesions was associated with an increased risk of progression to higher grade. This study aimed to investigate aPKCλ/ι expression patterns in cervical squamous cell carcinoma (SCC) and its association with disease progression. We immunohistochemically assessed aPKCλ/ι expression in 168 SCC samples and 13 normal uterine cervix samples. In 69.0% of SCC cases, aPKCλ/ι was expressed more abundantly than in normal epithelium, but there was no significant association between aPKCλ/ι intensity and disease progression (P=0.087, Cochran-Mantel-Haenszel test). aPKCλ/ι in normal cervical epithelium was confined to the cytoplasm or intercellular junctions. In contrast, aPKCλ/ι was predominantly localized within the nucleus in 36.9% of SCC samples (P<0.001, χ2 test), and the prevalence was significantly increased relative to advanced tumor stage (P<0.001, Cochran-Mantel-Haenszel test). Moreover, patients with SCC with aPKCλ/ι nuclear localization had worse prognoses than those with cytoplasmic localization (P<0.001, log-rank test). aPKCλ/ι localization differed between the intraepithelial lesion and adjacent invasive cancer in 40% of cases, while the expression pattern was similar between primary and matched metastatic tumors. In conclusion, aPKCλ/ι nuclear localization in cervical cancer is associated with tumor progression and worse prognosis. This is the first report to show aberrant nuclear aPKCλ/ι localization in a subgroup of cervical cancer patients and its association with worse prognosis.
A Critique of the Impact Factor and Ramifications of Its Misuse in Plastic and Reconstructive Surgery: The Real Impact of the Impact Factor
Authors: Nair Lakshmi , Adetayo Oluwaseun A.
Published: July 2018

The impact factor is used to compare the number of citations of a journal with its number of publications. Although first used to assess the significance of various journals, its very creator has stated that it is an imperfect system. Presently, the impact factor overvalues the importance of large-readership journals and undervalues that of smaller more specialized journals. Although no metric can serve as a perfect assessment of a journal’s worth, it is vital when selecting journals for publication, resource allocation, funding, or citation to weigh not only the impact factor of a large-volume journal, but also the added value of lower impact factor but also effective specialized subspecialty journals.
Predictive Features for Anterior Mediastinal Mass Diagnoses
Authors: Hammer Mark M. , Miskin Nityanand , Madan Rachna , Hunsaker Andetta R
Published: July 2018

Objective

We set out to evaluate a set of demographic and computed tomography imaging features for diagnosing anterior mediastinal masses.

Methods

We identified 223 patients with anterior mediastinal masses, which we divided into training and validation sets. One radiologist evaluated computed tomography imaging features on the training set. Then, predictive features were identified, and 3 radiologists evaluated these on the validation set. A naive Bayesian classifier based on the features was compared with the radiologists' first-choice diagnosis.

Results

Internal mammary lymphadenopathy and mediastinal encasement were strongly associated with lymphomas. Low attenuation and midline location were strongly associated with benign lesions, and older age was associated with thymic epithelial neoplasms. The average accuracy of the 3 radiologists' diagnoses was 78%, compared with 71% for the classifier.

Conclusions

Nine demographic and imaging features were found to be helpful in diagnosing anterior mediastinal masses. By using these features, radiologists can suggest the diagnosis with fair accuracy.
Surgical Pitfalls in Carotid Endarterectomy: A New Step-By-Step Approach
Authors: Denli Yalvac Emine Seyma , Baran Oguz , Aydin Aysegul Esen , Balak Naci , Tanriover Necmettin
Published: July 2018

Carotid endarterectomy (CEA) is a surgical intervention that may prevent stroke in asymptomatic and symptomatic patients. Our aim was to examine the microsurgical anatomy of carotid artery and other related neurovascular structures to summarize the CEA that is currently applied in ideal conditions. The upper necks of 2 adult cadavers (4 sides) were dissected using ×3 to ×40 magnification. The common carotid artery, external carotid artery (ECA), and internal carotid artery were exposed and examined. The surgical steps of CEA were described using 3-D cadaveric photos and computed tomography angiographic pictures obtained with help of OsiriX imaging software program. Segregating certain neurovascular and muscular structures in the course of CEA significantly increased the exposure. The division of facial vein allowed for internal jugular vein to be mobilized more laterally and dividing the posterior belly of digastric muscle resulted in an additional dorsal exposure of almost 2 cm. Isolating the ansa cervicalis that pulls hypoglossal nerve inferiorly allowed hypoglossal nerve to be released safely medially. The locations of the ECA branches alter depending on their anatomical variations. The hypoglossal nerve, glossopharyngeal nerve, and accessory nerve pierce the fascia of the upper part of the carotid sheath and they are vulnerable to injury because of their distinct courses along the surgical route. Surgical exposure in CEA requires meticulous dissection and detailed knowledge of microsurgical anatomy of the neck region to avoid neurovascular injuries and to determine the necessary surgical maneuvers in cases with neurovascular variations.
Orbital Emphysema: A Rare Postoperative Complication
Authors: Fernandes Breno dos Reis , Mulinari-Santos Gabriel , Okamoto Roberta , Neto Oswaldo Belloti , Mandarino Sydney , Silva Jonathan , Pereira Rodrigo dos Santos
Published: July 2018

Orbital emphysema can be a rare and severe postoperative complication. Fast and critical diagnosis is essential to avoid permanent visual loss to the patient. Therefore, a case of a male patient victim of a motorcycle accident with a postoperative complication of orbital emphysema has been presented. The immediate diagnosis and treatment of the orbital emphysema revealed to be the main success factors for the resolution of this complication.
Facilitating Preliteracy Development in Children With Hearing Loss When the Home Language Is Not English
Authors: Alfano Alliete R. , Douglas Michael
Published: July 2018

Prior research shows that preliteracy development of children with a hearing loss from homes where English is not the primary language parallels literacy development in children with hearing loss from monolingual homes. Although there are some parallels, there are also some elements that are unique to children from linguistically diverse, bilingual backgrounds. Understanding these commonalities and differences sets the stage to discuss appropriate interventions to develop language and literacy. Literacy-based interventions used with bilingual children who do not have a hearing loss, and/or with bilingual children with additional challenges, are explored for their implications for developing language and literacy in children with hearing loss when the home language is not English.
ACBD3 is an essential pan-enterovirus host factor that mediates the interaction between viral 3A protein and cellular protein PI4KB
Authors: Lyoo Heyrhyoung , van der Schaar Hilde M. , Dorobantu Cristina M. , Strating Jeroen R.P.M. , van Kuppeveld Frank J.M.
Published: July 2018

The enterovirus genus of the picornavirus family includes a large number of important human pathogens such as poliovirus, coxsackievirus, enterovirus-A71, and rhinoviruses. Like all other positive-strand RNA viruses, genome replication of enteroviruses occurs on rearranged membranous structures called replication organelles (ROs). Phosphatidylinositol 4-kinase IIIβ (PI4KB) is required by all enteroviruses for RO formation. The enteroviral 3A protein recruits PI4KB to ROs, but the exact mechanism remains elusive. Here, we investigated the role of Acyl-coenzyme A binding domain containing 3 (ACBD3) in PI4KB recruitment upon enterovirus replication using ACBD3-knockout (ACBD3KO) cells. ACBD3 knockout impaired replication of representative viruses from four enterovirus and two rhinovirus species. PI4KB recruitment was not observed in the absence of ACBD3. The lack of ACBD3 also affected the localization of individually expressed 3A, causing 3A to localize to the endoplasmic reticulum instead of the Golgi. Reconstitution of wt ACBD3 restored PI4KB recruitment and 3A localization, while an ACBD3 mutant that cannot bind to PI4KB restored 3A localization, but not virus replication. Consistently, reconstitution of a PI4KB mutant that cannot bind ACBD3 failed to restore virus replication in PI4KBKO cells. Finally, by reconstituting ACBD3 mutants lacking specific domains in ACBD3KO cells, we show that Acyl-coenzyme A binding (ACB) and charged amino acids region (CAR) domains are dispensable for 3A-mediated PI4KB recruitment and efficient enterovirus replication. Altogether, our data provide new insight into the central role of ACBD3 in recruiting PI4KB by enterovirus 3A and reveal the minimal domains of ACBD3 involved in recruiting PI4KB and supporting enterovirus replication.

Importance

As all other RNA viruses, enteroviruses reorganize host cellular membranes for efficient genome replication. A host lipid kinase, PI4KB, plays an important role on this membrane rearrangement. The exact mechanism of how enteroviruses recruit PI4KB was unclear. Here, we revealed a role of a Golgi-residing protein, ACBD3, as a mediator of PI4KB recruitment upon enterovirus replication. ACBD3 is responsible for proper localization of enteroviral 3A proteins in host cells which is important for 3A to recruit PI4KB. By testing ACBD3 and PI4KB mutants that abrogate the ACBD3-PI4KB interaction, we showed that this interaction is crucial for enterovirus replication. The importance of specific domains of ACBD3 was evaluated for the first time, and the essential domains for enterovirus replication were identified. Our findings open up a possibility for targeting ACBD3 or its interaction with virus as a novel strategy for a broad-spectrum antiviral drug.
A comparative study of machine learning algorithms in predicting severe complications after bariatric surgery
Authors: Cao Yang , Fang Xin , Ottosson Johan , Näslund Erik , Stenberg Erik
Published: July 2018

Accurate models to predict severe postoperative complications could be of value in the preoperative assessment of potential candidates for bariatric surgery. Traditional statistical methods have so far failed to produce high accuracy. To find a useful algorithm to predict the risk for severe complication after bariatric surgery, we trained and compared 29 supervised machine learning (ML) algorithms using information from 37,811 patients operated with a bariatric surgical procedure between 2010 and 2014 in Sweden. The algorithms were then tested on 6,250 patients operated in 2015. Most ML algorithms showed high accuracy (>90%) and specificity (>0.9) in both the training and test data. However, none achieved an acceptable sensitivity in the test data. ML methods may improve accuracy of prediction but we did not yet identify one with a high enough sensitivity that can be used in clinical praxis in bariatric surgery. Further investigation on deeper neural network algorithms is needed.
Introduce a New Approach to Detect Genes Associated to Oral Squamous Cell Carcinoma
Authors: Li Jianqiang , Yang Caiyun , Ji-Jiang Yang , Chen Shi , Wang Qing , HuiPan  , Liang Siyuan , Qiu Weiliang
Published: July 2018

Oral squamous cell carcinoma (OSCC) represents the most frequent of all oral neoplasms in the world. Genetics plays an important role in the etiopathogenesis of OSCC. However, the investigation of the molecular mechanism of OSCC is still incomplete. In this article, we introduced a new approach to detect OSCC-associated genes, in which we not only compare mean difference, but also variance difference between cases and controls. Based on two OSCC datasets from Gene Expression Omnibus, we identified 456 differentially variable (DV) gene probes, in addition to 2,375 differentially expressed (DE) gene probes. There are 2,193 DE-only probes, 274 DV-only probes, and 182 DE-and-DV probes. DAVID functional analysis showed that genes corresponding to DE-only, DV-only, and DE-and-DV probes were enriched in different KEGG pathways, indicating they play different roles in OSCC. This new approach can be used to investigate the genetic risk factors for other complex human diseases.
Autoimmunity to hypocretin and molecular mimicry to flu antigens in Type 1 narcolepsy
Authors: Luo Guo , Ambati Aditya , Lin Ling , Bonvalet Mélodie , Partinen Markku , Ji Xuhuai , Maecker Holden Terry , Mignot Emmanuel Jean-Marie
Published: July 2018

Type 1 narcolepsy (T1N) is caused by hypocretin (HCRT) neuronal loss. Association with the Human Leukocyte Antigen (HLA)-DQB1*06:02/DQA1*01:02 (98% vs 25%) heterodimer (DQ0602), T cell receptor (TCR) and other immune loci suggest autoimmunity but autoantigen(s) are unknown. Onset is seasonal and associated with influenza A, notably pandemic 2009 H1N1 (pH1N1). An extensive unbiased DQ0602 binding peptide screen was performed encompassing peptides derived from Pandemrix®X-179-A pH1N1 influenza-A vaccine, a known T1N trigger, other H1N1 strains, and potential human autoantigens HCRT and RFX4, identifying 109 binders. The presence of cognate tetramer-peptide specific CD4+T cells was studied in 35 narcolepsy cases and 22 DQ0602 controls after expansion of antigen-specific cells in Peripheral Blood Monocytes Cell (PBMC) cultures. Higher reactivity to influenza epitopes pHA273-287(pH1N1 specific) and PR8 (H1N1 pre 2009)-specific NP17-31were observed in T1N. Extensive reactivity to C-amidated but not native version of HCRT54-66and HCRT86-97, which are two highly homologous peptides (HCRTNH2) was observed with higher frequencies of specific T cells in T1N. TCRα/β CDR3 sequences found in pHA273-287,NP17-31and HCRTNH2tetramer positive CD4+cells were also retrieved in single INFγ-secreting CD4+sorted cells stimulated with Pandemrix®, confirming immunodominance and functional significance in DQ0602-mediated responses and molecular mimicry. TCRα/β CDR3 motifs of HCRT54-66and HCRT86-97tetramers were extensively shared. Particularly notable was sharing across subjects of an CDR3α, CAVETDSWGKLQF (in association with various CDR3β that used TRAJ24, a chain modulated by Single Nucleotide Polymorphism (SNPs) rs1154155 and rs1483979 associated with T1N. Sharing of CDR3β CASSQETQGRNYGYTF (in association with various CDR3α was also observed with HCRTNH2and pHA273-287-tetramers across subjects. This segment uses TRBV4-2, a segment modulated by narcolepsy-associated SNP rs1008599. Higher HCRTNH2positive CD4+T cell numbers in T1N together with sharing of J24 CAVETDSWGKLQF in HCRTNH2autoimmune responses, indicates causal DQ0602-mediated CD4+autoreactivity to HCRT in T1N. Our results provide evidence for autoimmunity and molecular mimicry with flu antigens modulated by genetic components in the pathophysiology of T1N.
Identifying Gait Phases from Joint Kinematics during Walking with Switched Linear Dynamical Systems
Authors: Drnach Luke , Essa Irfan , Ting Lena H.
Published: July 2018

Human-robot interaction (HRI) for gait rehabilitation could benefit from data-driven, subject-specific gait models that account for gait phases and gait dynamics. Here we address the current limitation in gait models driven by averaged kinematic data, which do not model interlimb gait dynamics and have not been shown to precisely identify gait events. We used Switched Linear Dynamical Systems (SLDS) to model joint angle kinematic data from healthy individuals walking on a treadmill during normal gait and during gait perturbed by electrical muscle stimulation. We compared model-inferred gait phases to gait phases measured independently via a force plate. We found that SLDS models accounted for over 88% of the variation in each joint angle and labeled the joint kinematics with the correct gait phase with 84% precision on average. The transitions between hidden states matched measured gait events, with a median absolute difference of 25ms. To our knowledge, this is the first time that SLDS inferred gait phases have been validated by an external measure of gait, instead of against pre-defined gait phase durations. SLDS provide individual-specific representations of gait that incorporate both gait phases and gait dynamics. SLDS may be useful for developing control policies for HRI aimed at improving gait by allowing for changes in control to be precisely timed to different gait phases.
Mutations in ELAC2 associated with hypertrophic cardiomyopathy impair mitochondrial tRNA 3’-end processing
Authors: Saoura Makenzie , Powell Christopher A. , Kopajtich Robert , Alahmad Ahmad , AL-Balool Haya H. , Albash Buthaina , Alfadhel Majid , Alston Charlotte L. , Bertini Enrico , Bonnen Penelope , Bratkovic Drago , Carrozzo Rosalba , Donati Maria A. , Nottia Michela Di , Ghezzi Daniele , Goldstein Amy , Haan Eric , Horvath Rita , Hughes Joanne , Invernizzi Federica , Lamantea Eleonora , Lucas Benjamin , Pinnock Kyla-Gaye , Pujantell Maria , Rahman Shamima , Rebelo-Guiomar Pedro , Santra Saikat , Verrigni Daniela , McFarland Robert , Prokisch Holger , Taylor Robert W. , Levinger Louis , Minczuk Michal
Published: July 2018

Dysfunction of mitochondrial gene expression, caused by mutations in either the mitochondrial or nuclear genomes, is associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA metabolism. For instance, pathogenic mutations have been identified in the genes encoding enzymes involved in the precursor transcript processing, including ELAC2. The ELAC2 gene codes for the mitochondrial RNase Z, which is responsible for endonucleolytic cleavage of the 3’ ends of mitochondrial pre-tRNAs. Here, we report the identification of sixteen novel ELAC2 variants in individuals presenting with mitochondrial respiratory chain deficiency, hypertrophic cardiomyopathy and lactic acidosis. We provided further evidence for the pathogenicity of the three previously reported variants by studying the RNase Z activity in an in vitro system and applied this recombinant system to investigate all novel missense variants, confirming the pathogenic role of these new ELAC2 mutations. We also modelled the residues affected by missense mutation in solved RNase Z structures, providing insight into enzyme structure and function. Finally, we show that primary fibroblasts from the individuals with novel ELAC2 variants have elevated levels of unprocessed mitochondrial RNA precursors. Our study thus broadly confirms the correlation of ELAC2 variants with severe infantile-onset forms of hypertrophic cardiomyopathy and mitochondrial respiratory chain dysfunction. One rare missense variant associated with the occurrence of prostate cancer (p.Arg781His) impairs the mitochondrial RNase Z activity of ELAC2, possibly indicating a functional link between tumorigenesis and mitochondrial RNA metabolism.
Single-cell molecular connectomics of intracortically-projecting neurons
Authors: Klingler Esther , Prados Julien , Kebschull Justus M , Dayer Alexandre , Zador Anthony M , Jabaudon Denis
Published: July 2018

The neocortex is organized into distinct areas, whose interconnectivity underlies sensorimotor transformations and integration1–7. These behaviorally critical functions are mediated by intracortically-projecting neurons (ICPN), which are a heterogeneous population of cells sending axonal branches to distinct cortical areas as well as to subcortical targets8–10. Although population-based11–14 and single-cell15–19 intracortical wiring diagrams are being identified, the transcriptional signatures corresponding to single-cell axonal projections of ICPN to multiple sites remain unknown. To address this question, we developed a high-throughput approach, “ConnectID”, to link connectome and transcriptome in single neurons. ConnectID combines MAPseq projection mapping17,20 (to identify single-neuron multiplex projections) with single-cell RNA sequencing (to identify corresponding gene expression). Using primary somatosensory cortex (S1) ICPN as proof-of-principle neurons, we identify three cardinal targets: (1) the primary motor cortex (M1), (2) the secondary somatosensory cortex (S2) and (3) subcortical targets (Sub). Using ConnectID, we identify transcriptional modules whose combined activities reflect multiplex projections to these cardinal targets. Based on these findings, we propose that the combinatorial activity of connectivity-defined transcriptional modules serves as a generic molecular mechanism to create diverse axonal projection patterns within and across neuronal cell types.
A synthetic microbial loop for modelling heterotroph-phototroph metabolic interactions
Authors: Fondi Marco , Di Patti Francesca
Published: July 2018

Marine ecosystems are characterized by an intricate set of interactions among their representatives. One of the most important occurs through the exchange of dissolved organic matter (DOM) provided by phototrophs and used by heterotrophic bacteria as their main carbon and energy source. This metabolic interaction represents the foundation of the entire ocean food-web.

Here we have assembled a synthetic ecosystem to assist the systems-level investigation of this biological association. This was achieved building an integrated, genome-scale metabolic reconstruction using two model organisms (a diatom Phaeodactylum tricornutum and an heterotrophic bacterium, Pseudoalteromonas haloplanktis) to explore and predict their metabolic interdependencies. The model was initially analysed using a constraint-based approach (Flux Balance Analysis, FBA) and then turned into a dynamic (dFBA) model to simulate a diatom-bacteria co-culture and to study the effect of changes in growth parameters on such a system. Finally, we developed a simpler dynamic ODEs system that, fed with dFBA results, was able to qualitatively describe this synthetic ecosystem and allowed performing stochastic simulations to assess the effect of noise on the overall balance of this co-culture.

We show that our model recapitulates known metabolic cross-talks of a phototroph-heterotroph system, including mutualism and competition for inorganic ions (i.e. phosphate and sulphate). Further, the dynamic simulation predicts realistic growth rate for both the diatom and the bacterium and a steady state balance between diatom and bacterial cell concentration that matches those determined in experimental co-cultures. This steady state, however, is reached following an oscillatory trend, a behaviour that is typically observed in the presence of metabolic co-dependencies. Finally, we show that, at high diatom/bacteria cell concentration ratio, stochastic fluctuations can lead to the extinction of bacteria from the co-culture, causing the explosion of diatom population. We anticipate that the developed synthetic ecosystem will serve in the future as a basis for the generation of testable hypotheses and as a scaffold for integrating and interpreting-omics data from experimental co-cultures.
Micro-foundations of innovation
Authors: Maqbool Saif , Černe Matej , Bortoluzzi Guido
Published: July 2018

Purpose

The purpose of this paper is to extend current discussion on the drivers of innovative work behaviour (IWB) of individuals by connecting theories of flow (personal factor), employee silence (relational) and time pressure (contextual).

Design/methodology/approach

Data have been collected from employees of five companies based in Italy (n=608).

Findings

Silence is negatively related to IWB, whereas flow has the opposite association. Perceived time pressure moderates the relationship between employee silence and IWB. Furthermore, the findings indicate that the highest levels of IWB will take place when the flow level is high, individuals are absorbed in and enjoy their work, and the level of employee silence is low, enabling them to exchange ideas and obtain the necessary support and resources. At the same time, low levels of time pressure provide them with sufficient time for innovative processes to take place, ideas to be shared, and individuals to become engrossed in their innovations.

Research limitations/implications

Cross-sectional single-source data set.

Practical implications

Establishing a work context favourable for stimulating each employee’s active contribution towards IWB based on a complex interaction among flow, silence and time pressure.

Originality/value

Building on the theories of flow and the relational model of employee silence and combining their logic, the research not only delves into the two specific paths to IWB but also examines their multiple effects. Furthermore, the authors pin both factors (silence and flow) under the contextual influence of perceived time pressure, investigating how they simultaneously relate to IWB.
TEFL/TESOL teachers on the move: mobility and culture
Authors: Lam Lydia Sin Ting
Published: July 2018

Purpose

The purpose of this paper is to discuss the story of 15 TEFL/TESOL English language teachers who spend their lives working globally.

Design/methodology/approach

Interviews from the research based on the grounded approach generated, among others, three inter-related themes, namely, the global drift, distinctive cultural dispositions and the concept of global quality.

Findings

The global drift symbolizes interviewees’ mobility pattern and captures their Hong Kong experience in four states – adaptation, drifting in global comfort, drifting in global discomfort and bitter/sweet home, each representing a different quality of mobility which contributes to the development of cultural dispositions. Findings of cultural disposition home and openness are considered in relation to studies of its kind. Four aspects of home perceptions in the data are identified. While interviewees developed complex and varied notions of home, it is argued that the geographical home remains a significant resource in the making of home. Data also suggest that most interviewees’ openness is limited – it is selective, functional and transient. Global quality, a concept emerged from the research, summarizes the distinctive cultural traits of the community of the globals. It overlaps with, but does not necessarily equate with, cosmopolitanism.

Originality/value

The conclusion relates the study, including the concepts generated from this research, to cosmopolitanism. Two theoretical constructs are employed in the analysis: form of mobility and nature of mobility.
Cost and time implications of abandoned project resuscitation
Authors: Alao Oluwaseyi Olalekan , Jagboro Godwin Onajite , Opawole Akintayo
Published: July 2018

Purpose

This paper aims to determine the effect of the period of abandonment on the final cost and duration of resuscitated tertiary educational building projects as a basis for enhancing the performance metrics of the projects and improving the availability of facilities in tertiary institutions in Nigeria.

Design/methodology/approach

A structured questionnaire was administered on 47 professionals involved in the physical development of construction projects in Osun State public tertiary educational institutions to provide primary data for the study. Secondary data relating to initial and final costs, initial and final completion dates, dates of abandonment, period of abandonment, date of re-award, etc. were obtained from selected resuscitated projects. Data were analyzed using relative significance index and regression analysis.

Findings

The most significant effects of project abandonment were found to be disappointment of populace and over-stretching of existing facilities. The study showed a directly proportional and an exponential effect of period of abandonment on percentage cost overrun of resuscitated projects, which were represented by yc = −329.755 + 19.545x and yc = 6.1662e0.0506x, respectively. A linear relationship between period of abandonment and percentage time overrun was represented by yt = 0.467 + 0.816x.

Research limitations/implications

The fact that the regression equations could not be validated because of paucity of data was identified as a limitation of this study.

Practical implications

This study adds to the body of knowledge on abandonment of building projects from a quantitative perspective. Findings have implications for guiding long-term infrastructure development plans in public tertiary educational institutions.

Originality/value

Maximum threshold at which abandoned projects may be resuscitated at an economic cost was established as 16 months. Findings further suggest that the economy of new construction would outweigh resuscitation of abandoned projects beyond this period.
Enablers of relational integrated value networks (RIVANS) for total facilities management (TFM)
Authors: De Silva Nayanthara , Weerasinghe Nilmini , Madhusanka H.W.N. , Kumaraswamy Mohan
Published: July 2018

Purpose

The purpose of this paper is to identify enablers for setting up relationally integrated value networks (RIVANS) for total facilities management (TFM) as a holistic approach to bridge the Project Management (PM) phase to the facilities management (FM) phase, aiming for better service delivery while optimizing the life-cycle cost. These enablers are proposed as required driving forces for the industry to bridge current gaps through RIVANS for TFM so as to improve the value of the facility and deliver better value to its stakeholders over its life span.

Design/methodology/approach

A literature review elicited 11 typical better values that could be achieved by suitably linking the PM and FM supply chains in general. While these were tested in parallel research exercises in Hong Kong, the UK and Singapore, this paper reports on the specific findings from Sri Lanka, where a Web-based questionnaire survey was conducted to identify potential better values for proposed relational networks (including the clients, consultants, contractors and suppliers in the supply chain). Better values were then clustered under principal domains/components using factor analysis to establish synergetic enablers.

Findings

In total, 11 significant better values for TFM were identified and four enablers were extracted as building long-term integrated networks, establishing a common resource pool linking PM and FM, enhancing sustainability of TFM and developing a similar protocol between PM and FM.

Originality/value

The study carried out in this paper contributes to knowledge by identifying drivers to bridge the gap between PM and FM to best achieve clients’ long-term aspirations through a holistic life-cycle approach. Furthermore, all stakeholders in TFM can revisit their practices to establish and strengthen the identified enablers.