bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical outcomes of subtotal colectomy with antiperistaltic caecorectal anastomosis vs total colectomy with ileorectal anastomosis for intractable slow-transit constipation
Authors: Xie Xiao-Yu , Sun Kong-Liang , Chen Wen-Hao , Zhou Yan , Chen Bao-Xiang , Ding Zhao , Yu Xue-Qiao , Wu Yun-Hua , Qian Qun , Jiang Cong-Qing , Liu Wei-Cheng
Published: March 2019

Background

Few studies have compared the surgical outcomes of different surgical procedures currently used to treat refractory colonic slow-transit constipation (STC), despite the increase in the number of cases. This study aimed to analyse the long-term surgical outcomes of subtotal colectomy with antiperistaltic caecorectal anastomosis (SC-ACRA) vs total colectomy with ileorectal anastomosis (TC-IRA) for severe STC.

Methods

Between January 2005 and January 2015, we retrospectively collected clinical data of 55 patients who underwent TC-IRA (n = 35) or SC-ACRA (n = 20) for severe STC at our institution. The post-operative functional outcomes between the two groups were compared.

Results

There were no significant differences in age (P = 0.655), sex (P = 0.234), period of constipation (P = 0.105) and defecation frequency (P = 0.698) between the TC-IRA and SC-ACRA groups. During a median follow-up period of 72 months (range, 12–120 months), there were no significant differences between the TC-IRA and SC-ACRA groups regarding the median number of bowel movements per day [3 (1/6–7) vs 3 (1/6–5), P = 0.578], Cleveland Clinic Florida Constipation Score [2 (0–20) vs 2 (0–19), P = 0.454], Cleveland Clinic Incontinence Score [0 (0–5) vs 0 (0–2), P = 0.333] and Gastrointestinal Quality of Life Index [122 (81–132) vs 120 (80–132), P = 0.661]. Moreover, there was no significant difference in the incidence of post-operative complications between the two groups (37.1% vs 25.0%, P = 0.285).

Conclusions

Our findings indicate that both TC-IRA and SC-ACRA are effective treatments for severe STC, with similar long-term outcomes.
On the Success of the Hadal Snailfishes
Authors: Gerringer M E
Published: March 2019

Synopsis

Deep-sea trenches, depths 6000–11,000 m, are characterized by high pressures, low temperatures, and absence of sunlight. These features make up the majority of the deepest marine habitat—the hadal zone—home to distinct communities from those in the surrounding abyssal plains. The snailfishes, family Liparidae (Scorpaeniformes), have found notable success in the hadal zone from ∼6000 to 8200 m, comprising the dominant ichthyofauna in at least six trenches worldwide. The hadal fish community is distinct from the abyssal community where elongate, scavenging fishes such as rattails (Macrouridae), cutthroat eels (Synaphobranchidae), tripodfishes (Ipnopidae), eelpouts (Zoarcidae), and cusk eels (Ophidiidae) are most common. Until recently, little was known about the biology of these deepest-living fishes, or the factors that drive their success at hadal depths. Here, I review recent investigations spanning the abyssal–hadal boundary and discuss the factors structuring these communities, including the roles of pressure adaptation, feeding ecology, and life history. Hadal fishes show specialized adaptation to hydrostatic pressure both in accumulation of the pressure-counteractant trimethylamine n-oxide and in intrinsic changes to enzymes. Stomach content and amino acid isotope analyses, and jaw morphology suggest that suction-feeding predatory fishes like hadal liparids may find an advantage to descending into the trench where amphipods are increasingly abundant. Analysis of otolith growth zones suggest that snailfishes may be adapted to a seismically active, high-disturbance hadal environment by having relatively short life-spans. This review synthesizes the known literature on the planet’s deepest-living fishes and informs new understanding of adaptations to life in the trenches.
Electronic health record (EHR) training program identifies a new tool to quantify the EHR time burden and improves providers’ perceived control over their workload in the EHR
Authors: DiAngi Yumi T , Stevens Lindsay A , Halpern – Felsher Bonnie , Pageler Natalie M , Lee Tzielan C
Published: March 2019

Objective

To understand if providers who had additional electronic health record (EHR) training improved their satisfaction, decreased personal EHR-use time, and decreased turnaround time on tasks.

Materials and Methods

This pre-post study with no controls evaluated the impact of a supplemental EHR training program on a group of academic and community practice clinicians that previously had go-live group EHR training and 20 months experience using this EHR on self-reported data, calculated EHR time, and vendor-reported metrics.

Results

Providers self-reported significant improvements in their knowledge of efficiency tools in the EHR after training and doubled (significant) their preference list entries (mean pre = 38.1 [65.88], post = 63.5 [90.47], P < .01). Of the 7 EHR satisfaction variables, only 1 self-reported variable significantly improved after training: Control over my workload in the EHR (mean pre = 2.7 [0.96], post = 3.0 [1.04], P < .01). There was no significant decrease in their calculated EHR usage outside of clinic (mean pre = 0.39 [0.77] to post = 0.37 [0.48], P = .73). No significant difference was seen in turnaround time for patient calls (mean pre = 2.3 [2.06] days, post = 1.9 [1.76] days, P = .08) and results (mean before = 4.0 [2.79] days, after = 3.2 [2.33] days, P = .03).

Discussion

Multiple sources of data provide a holistic view of the provider experience in the EHR. This study suggests that individualized EHR training can improve the knowledge of EHR tools and satisfaction with their perceived control of EHR workload, however this did not translate into less Clinician Logged-In Outside Clinic (CLOC) time, a calculated metric, nor quicker turnaround on in box tasks. CLOC time emerged as a potential less-costly surrogate metric for provider satisfaction in EHR work than surveying clinicians. Further study is required to understand the cost-benefit of various interventions to decrease CLOC time.

Conclusions

This supplemental EHR training session, 20 months post go-live, where most participants elected to receive 2 or fewer sessions did significantly improve provider satisfaction with perceived control over their workload in the EHR, but it was not effective in decreasing EHR-use time outside of clinic. CLOC time, a calculated metric, could be a practical trackable surrogate for provider satisfaction (inverse correlation) with after-hours time spent in the EHR. Further study into interventions that decrease CLOC time and improve turnaround time to respond to inbox tasks are suggested next steps.
Mapping Modern Rejuvenation: An Introduction
Authors: Alexander Kristine , Honeck Mischa , Richter Isabel
Published: March 2019

The desire to conquer old age is as old as humanity itself, yet the pursuit of youthfulness acquired a fiercer urgency with the rise of post-Enlightenment conceptions of youth as a redemptive social force. This introductory essay widens the circle of what constitutes modern rejuvenation by moving beyond the standard focus on anti-aging medicine and lays out the historiographical and methodological stakes of conceptualizing rejuvenation more broadly. Its main contention is that rejuvenation can serve as an analytical linchpin to reveal unrecognized connections between various historically specific projects of regeneration and repair that were comprised in individual flesh-and-blood as well as in imagined collective bodies such as nations and empires.
Posterior Fossa Decompression With or Without Duraplasty in the Treatment of Paediatric Chiari Malformation Type I: A Literature Review and Meta-Analysis
Authors: Honeyman Susan I , Warr William
Published: March 2019

INTRODUCTION

Chiari malformation I (CM-1) is a posterior fossa structural abnormality, characterized by caudal displacement of cerebellar tonsils, through the foramen magnum.

Posterior fossa decompression (PFD), involving a suboccipital craniectomy and C1 laminectomy, remains the definitive treatment. Both PFD alone (PFDO) and PFD with additional duraplasty (PFDD) are used in surgical practices. This review evaluates the current literature comparing outcomes of CM-1 treatment using PFDO and PFDD.

METHODS

A literature search of EMBASE and MEDLINE was conducted. References from January 1980 to January 2018 were retrieved. Only papers containing original data, comparing the use of PFDD and PFDO in paediatric CM-1 patients, were included.

RESULTS

Eighteen relevant papers were identified, with a resulting cohort of 4030 patients, 46.1% underwent PFDD and 53.9% PFDO. PFDD was associated with 60 min longer mean operation duration, and longer mean hospital stays by 0.7 d. PFDD provided greater symptomatic improvement (OR: 2.13; 95% CI: 1.31-3.45; P = .002). However, PFDD was also associated with increased postoperative complications (OR: 1.71, 95% CI: 1.41-2.08; P = .0001), in particular CSF leak and meningitis. PFDD was not significantly associated with incidence of syrinx improvement or revision surgery, relative to PFDO.

CONCLUSION

From the current literature, PFDD is associated with greater clinical improvement but higher risk of postsurgical complications, in comparison to PFDO for the treatment of paediatric CM-1. The requirement for a large cohort prospective study, adjusting for case-mix, which evaluates the relative efficacy of these 2 techniques have been identified. Current evidence is low quality, with limited statistical power.
Predicting Non-Routine Discharge After Elective Spine Surgery: External Validation of Machine Learning Algorithms Using Institutional Data
Authors: Stopa Brittany M , Robertson Faith C , Karhade Aditya , Chua Melissa , Broekman Marike L D , Schwab Joseph H , Smith Timothy R , Gormley William B
Published: March 2019

INTRODUCTION

Non-routine discharge after elective spine surgery negatively impacts patient outcomes and increases healthcare costs. Preoperative prediction in this population could improve discharge planning. We previously developed an algorithm that predicts non-home discharge after elective spine surgery. Here, we validate our algorithm in an institutional population of neurosurgical spine patients from a Transitional Care Program (TCP) at an academic, tertiary care center.

METHODS

Medical records from elective inpatient surgery for lumbar disc herniation or degeneration in the TCP program (2013–2015) were retrospectively reviewed. Variables included age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) class, preoperative functional status, number of fusion levels and discharge disposition. The discrimination and calibration of the previous algorithm was assessed in the independent sample, using Python 3.0 software.

RESULTS

A total of 144 patients underwent elective inpatient surgery for lumbar disc disorders with a non-home discharge rate of 10 (7%). The algorithm generalized well to the institutional data with c-statistic 0.89, calibration slope 1.09 and calibration intercept −0.08. This was comparable to performance in the derivation cohort and substantiates initial use of this algorithm in clinical practice. Prospective validation of this algorithm and comparison to other existing discharge prediction models is ongoing.

CONCLUSION

This institutional external validation of a previously developed machine learning algorithm suggests a reliable method for identifying lumbar disc disorder patients at risk for non-routine discharge. This tool can be used by multidisciplinary teams of case management and spine surgeons to strategically invest additional time and resources into postoperative plans for this population.
Thirty-Day Mortality and Survival in Elderly Patients Undergoing Neurosurgery
Authors: Bligh Emily Rose , Al-Tamimi Yahia , Sinha Priyank , Smith Daisy
Published: March 2019

INTRODUCTION

With an ageing population and advances in neuroanaesthesia and critical care, there is an increasing subgroup of patients greater than 70 yr of age presenting to neurosurgical departments and undergoing surgery. We are now moving towards the idea of a frailty index. The aim of the current study is to investigate 30-d mortality and survival in this cohort following emergency and elective neurosurgery.

METHODS

Retrospective cohort study. All patients aged 70 yr and above, who had undergone a neurosurgical procedure from April 2015 to April 2017 were identified. Online patient electronic records were retrieved to gather information related to procedure type, co-morbidities, days in hospital, discharge destination, complications and mortality. Logistic regression analysis was used to identify predictors of mortality.

RESULTS

A total of 798 patients in total of whom 623 were <80 yr (group A) and 175 were >80 yr (group B). Male : Female = 3 : 1. Mean age of the study was 76 yr. There were 390 elective and 408 emergency admissions. Overall 30-d mortality = 5.6% (8% in group B). Overall survival was 86.5% in group A and 79.4% in group B. There was a significant difference in 30-d mortality between elective (0.8%) and emergency (10.3%) patients. About 84.5% of patients were discharged back to their usual place of residence in group A but this figure was 68.9% for group B. Logistic regression found emergency surgery (P > .001) and degenerative spine diagnosis to be independent predictors of mortality (P = .05).

CONCLUSION

The current model for accepting elderly patients is associated with a good overall outcome. The elderly should not be refused neurosurgery on their age per se. We have applied fairly strict and stringent criteria particularly in SAH and TBI.
Establishment of the European Medical Students' Neurosurgery Society–A Proposal
Authors: Stumpo Vittorio
Published: March 2019

INTRODUCTION

Recent years have witnessed the birth in the United States of Neurosurgery Medical Students Chapters aimed at fostering the interest toward neurosurgery and at supporting students willing to pursue a career in academic neurosurgery by making available research and mentoring opportunities. The American Association of Neurological Surgeons has pioneered the support of these programs and medical chapters are currently active in most US medical schools where they receive support from local Neurosurgery Departments and Research Centers. On the contrary, the European network of medical students' neurosurgical interest groups is fragmented and this opportunity is largely unexploited.

METHODS

The present abstract is intended to propose the establishment of the European Medical Students' Neurosurgery Society which would represent a tremendous opportunity to build a collaborative network and promote students' interest toward neurosurgery with the aim of increasing learning, research and mentoring opportunities.

RESULTS

The Italian Medical Student Neurosurgery Interest Group is currently underway and will be launched soon. Other medical students' societies active in European countries are invited to join this project to establish a proactive European Neurosurgical Student Network and to advocate the birth of other groups.

CONCLUSION

The establishment of this society under EANS support would represent the ideal platform for leadership positions in the medical student community at local and national level that will be important to acquire experience and promote a virtuous circle of knowledge and service while also providing the basis for scientific production on the current state of medical students' recruiting in neurosurgery around Europe.
Quantitative Diffusion Tensor Imaging (DTI) Analysis Reveals Different Infiltrative Patterns of Oligodendrogliomas and Astrocytomas in Peri-Tumour White Matter
Authors: Murphy Christopher , Agushi Erjon , Su Zhangjie , Hinz Rainer , Roncaroli Federico , Coope David
Published: March 2019

INTRODUCTION

Gliomas are highly infiltrative primary brain tumours. Glioma infiltration is difficult to identify clinically using conventional diagnostic imaging. We used diffusion tensor imaging (DTI) to identify glioma infiltration in peritumour white matter (WM) and characterized differences between histological subtypes.

METHODS

We recruited 8 patients with a histological diagnosis of grade II or III glioma and 10 healthy controls. We compared fractional anisotropy (FA) maps of each patient against the control group using SPM8 (Matlab 2014a) to identify regions of glioma infiltration. The FA and mean diffusivity (MD) of formerly WM matter tumour regions, infiltrated WM and normal appearing WM were compared with a 2-sample t-test and characterized with respect to normal control data.

RESULTS

Our results have identified radiological evidence of infiltration in the peri-tumour WM of glioma patients. The infiltrated region of oligodendrogliomas extended further than that of astrocytomas. Oligodendrogliomas preferentially infiltrated larger WM tracts, whereas astrocytomas infiltrated more peripheral WM. In all grades, the 3 regions had significantly different diffusion parameters and there were significant differences between oligodendrogliomas and astrocytomas.

CONCLUSION

We identified previously unrecognized study wide significant changes in the peri-tumour WM of gliomas. Despite the known propensity of these tumours to infiltrate WM we found no significant DTI changes distant to the tumour. Our DTI results suggest oligodendrogliomas and astrocytomas demonstrate different infiltrative patterns, which highlights the need for astrocytomas and oligodendrogliomas to be studied separately.
PET Imaging and Glioblastoma
Authors: Weigel Katharina
Published: March 2019

INTRODUCTION

Patients who present with Glioblastoma have a median survival of around 15 mo, even when treated with the most aggressive methods available. Imaging of glial cell tumours is faced with multiple challenges, including the accurate delineation of abnormal tissue and the identification of low-grade gliomas.

PET imaging depicts aspects of tissue activity in Vivo and thus, helps us improve our understanding of the tumor's size and behavior. While functional imaging is already an established modality in other fields of oncology, the appropriate tracer for the imaging of glial cancers remains under investigation since FDG, the traditional oncological tracer, proves suboptimal due to the high physiological glucose uptake of the cerebral grey matter.

METHODS

In this literature review, I discuss the physiological characteristics as well as the opportunities for clinical application of the tracers FDG, C-MET, FET, FDOPA and FLT.

RESULTS

Although PET imaging remains expensive and availability of tracers is limited by their mode of production and decaying nature, integration of PET scanning into the treatment pathway offers clear patient benefits. While sensitivity of the PET tracers C-MET and FET exceeds that of traditional imaging modalities, application in screening is limited by associated expenses. Combining amino-acid PET tracers with traditional modalities has shown significant benefits in biopsy and radiotherapy planning.

CONCLUSION

All amino acid tracers show good results in distinguishing treatment response from early recurrence, a task where MRI, the current gold standard, is lacking in reliability. FET shows especially good results in monitoring residual tumour mass.
Prognosticating Traumatic Brain Injury (TBI): Analysis of CRASH, IMPACT Models and Patient Age in a Cohort of TBI Patients
Authors: Gillespie Conor , McMahon Catherine
Published: March 2019

INTRODUCTION

Both CRASH and IMPACT models have been developed in recent years to predict the outcome of Traumatic Brain Injury (TBI). However, there is no clear evidence as to how these models perform in a modern cohort of UK-patients. There is also predictive uncertainty with regards to survival rates and functional outcome in elderly (>65 yr) patients.

METHODS

Patients referred to a tertiary neuroscience center from December 2014 to January 2016 with a suspected TBI were retrospectively examined. For each model, the predicted survival and overall outcome were compared to the actual outcome on admission and at 6 mo post injury, stratified by patient age (>65 yr vs ≤65 yr).

RESULTS

A total of 161 patients met the initial criteria; mean age 65 yr (SD = 21) and 110 male. Both CRASH and IMPACT correctly predicted 6-mo mortality rates and functional outcomes in most patients (range 61.7%-82.4%), with better predictive performance for patients not accepted to the center (range 84%-98%). There was no significant difference in the initial survival of elderly patients if accepted (78% [95% CI 50.6-104.0] vs 81% [95% CI 67.8-94.8] but were lower for those not accepted (24% [95% CI 4.2-43.7] vs 76% [95% CI 63.5-88.5], P = .027).

CONCLUSION

Patients >65 yr admitted to tertiary neuroscience center had good survival rates on admission and at 6 mo. The lesser ability of CRASH and IMPACT models to predict poorer outcomes when accepted suggests that acceptance to specialist centers may be able to improve outcome and suggests more optimistic treatment and acceptance of appropriate over 65 yr should be considered.
Economic Comparison Between Endovascular Coiling vs Neurosurgical Clipping for Ruptured and Unruptured Intracranial Aneurysms in Austria
Authors: Gryn Kateryna , Schaffhauser-Linzatti Michaela-Maria , Sherif Camillo
Published: March 2019

INTRODUCTION

Subarachnoid hemorrhage from a ruptured intracranial aneurysm poses a significant health hazard due to its high rates of mortality and disability. The 2 most commonly used treatment modalities of intracranial aneurysms are neurosurgical clipping and endovascular coiling. Through the decision on which treatment option should be chosen in every case is made based on medical indication, nevertheless, due to high socioeconomic burden of subarachnoid hemorrhage, it is also important to compare the healthcare expenditures, caused by clipping and coiling.

METHODS

A comparison of treatment costs of clipping, coiling and stent-assisted coiling (SAC) of ruptured and unruptured aneurysms in Austria was performed. We considered costs of surgery, diagnostic imaging, postoperative in-hospital care, treatment of the complications and initial rehabilitation. Cost-related data was provided by Vienna General Hospital. The length of hospital stay, complications and mortality rates were obtained from previous studies. Based on this information, a decision tree was built.

RESULTS

Surgery costs of coiling were significantly higher compared to clipping (13.303 98 Euro for Coiling and 24.847 63 Euro for SAC vs 6.835 23 Euro for Clipping). The main cost-driving factors were implants costs. However, clipping caused higher costs of in-hospital stay and initial rehabilitation. Altogether, when considering all in-hospital costs and the cost of rehabilitation treatment, the difference in costs of aneurysm clipping vs coiling was less pronounced.

CONCLUSION

This study is the first attempt to calculate the costs of aneurysm treatment in Austria. However, the economic comparison is partially based on estimations.
Time-Critical Transfers for Paediatric Neurosurgical Emergencies Operated on Out-of-Hours at a Tertiary Neurosurgical Centre: A Single Centre Experience
Authors: Rae Shivani , Hall Samuel , Sparrow Owen , Mathad Nijaguna , Waters Ryan , Chakraborty Aabir
Published: March 2019

INTRODUCTION

Recommendations suggest operating within 4 hr of acute brain injury. Centralization of paediatric neurosurgical and intensive care facilities therefore necessitates prompt assessment and transfer.

METHODS

A retrospective audit of out-of-hours operations at a tertiary neurosurgical center over 2013 to 2016 identified 36 patients (mean age 8 yr (SD = 5); male n = 21) from consultant records and case notes. Initial GCS, transfer timings and 3-mo Glasgow Outcome Score (GOS) were recorded.

RESULTS

A total of 36 emergency surgeries were performed: hematoma evacuation (n = 17), CSF diversion (n = 16), posterior fossa tumor debulking (n = 1), depressed skull fracture elevation (n = 1) and decompressive craniectomy (n = 1). Median GCS at presentation was 8.5 (range: 3-15). Twenty operations began within 4 hr of CT. Twenty-nine patients presented to district general hospitals, underwent imaging before transfer; their mean CT to arrival time was 197.8 (SD = 70.7) min and CT to operation time was 271.7 (SD = 123.1) min. Three-mo outcomes were: GOS 5 (n = 24), 4 (n = 5), 3 (n = 2) and 1 (n = 5); these were dichotomized into favorable (GOS 4–5) or unfavorable (GOS 1–3). Fisher's exact tests found no significant association between outcome favorability and timing of operation (whether within 4 hr of CT) (P = .43), or operation type (hematoma evacuation vs CSF diversion) (P = .22). Initial GCS did not significantly correlate with GOS (rs = 0.30, P = .10).

CONCLUSION

The majority of outcomes were favorable regardless of whether surgery occurred within 4 hr of CT. This suggests underlying pathology may have a greater impact on poor outcomes than the transfer time, highlighting the importance of early scanning and neurosurgical referral to facilitate prompt decision-making.
Freehand Insertion of External Ventricular Drainage Catheter–Evaluation of Accuracy in a Single Centre
Authors: Lee Keng Siang , Yeo Tseng Tsai , Chou Ning , Lwin Prof Sein , Teo Kejia , Nga Vincent , Bolem Nagarjun , Leong May Lian , Goh Chun Peng , Hassan Rashidul , Salek Maa
Published: March 2019

INTRODUCTION

External ventricular drain (EVD) placement is the gold standard for managing acute hydrocephalus. Freehand EVD, using surface anatomical landmarks is performed for ventricular cannulation due to its simplicity and efficiency. This study evaluates accuracy and reason(s) for misplacements as few studies have analyzed the accuracy of freehand EVD insertion.

METHODS

Preoperative and postoperative computed tomography (CT) scans of patients who underwent EVD insertion in 2014 were retrospectively reviewed. Diagnosis, Evan's ratio, midline shift, position of burr hole, length of the catheter and procedural complications were tabulated. The procedures were classified as satisfactory (catheter tip in the frontal horn ipsilateral lateral ventricle) and unsatisfactory. Unsatisfactory cases were further analyzed in relation to position of burr hole from midline and length of the catheter.

RESULTS

A total of 77 EVD placements in 70 patients were evaluated. Mean age of the patients was 57.5 yr. About 83.1% were satisfactory placements and 11.7% were unsatisfactory in the contralateral ventricle, corpus callosum and interhemispheric fissure. About 5.2% were in extra ventricular locations. About 2.6% EVD placements were complicated by hemorrhage and 1 catheter was reinserted. Suboptimal placements were significantly associated with longer intracranial catheter length. The mean length was 66.54 ± 10.1 mm in unsatisfactory placements compared to 58.32 ± 4.85 mm in satisfactory placements. Between the 2 groups, no significant difference was observed in Evan's ratio, midline shift, surgeon's experience, distance of burr hole from midline and coronal suture.

CONCLUSION

Freehand EVD insertion is safe and accurate. In small number of cases, unsatisfactory placement is related to longer catheter length.
Transgenic rhesus monkeys carrying the human MCPH1 gene copies show human-like neoteny of brain development
Authors: Shi Lei , Luo Xin , Jiang Jin , Chen Yongchang , Liu Cirong , Hu Ting , Li Min , Lin Qiang , Li Yanjiao , Huang Jun , Wang Hong , Niu Yuyu , Shi Yundi , Styner Martin , Wang Jianhong , Lu Yi , Sun Xuejin , Yu Hualin , Ji Weizhi , Su Bing
Published: March 2019

Brain size and cognitive skills are the most dramatically changed traits in humans during evolution and yet the genetic mechanisms underlying these human-specific changes remain elusive. Here, we successfully generated 11 transgenic rhesus monkeys (8 first-generation and 3 second-generation) carrying human copies of MCPH1, an important gene for brain development and brain evolution. Brain-image and tissue-section analyses indicated an altered pattern of neural-cell differentiation, resulting in a delayed neuronal maturation and neural-fiber myelination of the transgenic monkeys, similar to the known evolutionary change of developmental delay (neoteny) in humans. Further brain-transcriptome and tissue-section analyses of major developmental stages showed a marked human-like expression delay of neuron differentiation and synaptic-signaling genes, providing a molecular explanation for the observed brain-developmental delay of the transgenic monkeys. More importantly, the transgenic monkeys exhibited better short-term memory and shorter reaction time compared with the wild-type controls in the delayed-matching-to-sample task. The presented data represent the first attempt to experimentally interrogate the genetic basis of human brain origin using a transgenic monkey model and it values the use of non-human primates in understanding unique human traits.
Factors Associated With Nonadherence to Pelvic Floor Physical Therapy Referral for the Treatment of Pelvic Pain in Women
Authors: Aguirre Frank , Heft Jessica , Yunker Amanda
Published: March 2019

Background

Patients with pelvic pain due to pelvic floor myofascial pain syndrome are often referred for pelvic floor physical therapy, the primary treatment option. However, many patients do not adhere to the treatment.

Objective

The purpose of this study was to examine the adherence rate and outcomes of patients referred for physical therapy for pelvic floor myofascial pain syndrome and identify risk factors associated with nonadherence.

Design

This was a retrospective cohort study.

Methods

ICD-9 codes were used to identify a cohort of patients with pelvic floor myofascial pain syndrome during a 2-year time period within a single provider's clinical practice. Medical records were abstracted to obtain information on referral to physical therapy, associated comorbidities and demographics, and clinical outcomes. “Primary outcomes” was defined as attendance of at least 1 visit. Secondary outcomes included attendance of at least 6 physical therapist visits and overall improvement in pain. Statistical analysis was performed using chi-square, Fisher exact, and independent t tests. Nonparametric comparisons were performed using Wilcoxon signed rank test. Multivariate analysis was completed to adjust for confounders.

Results

Of the 205 patients, 140 (68%) attended at least 1 session with physical therapy. At least 6 visits were attended by 68 (33%) patients. Factors associated with poor adherence included parity and a preexisting psychiatric diagnosis. The odds of attending at least 1 visit were 0.75 (95% confidence interval = 0.62–0.90) and 0.44 (95% confidence interval = 0.21–0.90), respectively. Patients who attended ≥ 6 visits were more likely to have private insurance (78%) and travel shorter distances to a therapist (mean = 16 miles vs 22). Patients with an improvement in pain (compared with those who were unchanged) attended an average of 3 extra physical therapist visits (mean = 6.9 vs 3.1).

Limitations

Limitations include reliance on medical records for data integrity; a patient population derived from a single clinic, reducing the generalizability of the results; the age of the data (2010–2012); and the likely interrelatedness of many of the variables. It is possible that maternal parity and psychiatric diagnoses are partial surrogates for social, logistic, or economic constraints and patient confidence.

Conclusions

Initial adherence to pelvic floor physical therapy was less likely for multiparous women and women with a history of psychiatric diagnosis. Persistent adherence was more likely with private insurance or if the physical therapist location was closer. Pain improvement correlated with increased number of physical therapist sessions.
Effects of pen location on thermoregulation and growth performance in grow-finish pigs during late summer1
Authors: Kpodo Kouassi R , Duttlinger Alan W , Johnson Jay S
Published: March 2019

The effects of pen location on swine thermoregulation and growth performance were determined over 6 weeks during late summer. A total of 128 mixed sex pigs [Duroc × (Landrace × Yorkshire)] were randomly assigned to 16 pens in two grow-finish barns (n = 8 pens/barn; 57.43 ± 1.33 kg initial body weight (BW)). Pen locations were determined based on orientation to ventilation fans and air inlets. Internal pens (IP; n = 4/barn) were in direct line of sight between the fans and air inlets while peripheral pens (PP; n = 4/barn) were located 0.70 ± 0.29 m to either side of a fan. Two sentinel gilts per pen were selected and vaginal temperature (TV) was measured in 10-min intervals using TV data loggers. Additionally, trunk skin temperature (TS) was measured with an infrared camera and respiration rate (RR) was measured by counting flank movements of the sentinel gilts twice daily (0800 and 1500 hours). Pen airspeed was measured twice daily (0800 and 1500 hours) at pig level with an anemometer. Individual pen ambient temperature (TA) and relative humidity (RH) were recorded daily in 10-min intervals. Feed consumption and BW were determined every 2 weeks. Data were analyzed using PROC MIXED in SAS 9.4. Although airspeed was reduced overall (P = 0.01; 11%) in PP compared with IP, no differences (P > 0.10) in TA (27.53 ± 1.73 °C) or RH (68.47 ± 5.92%) were detected. An overall increase (P ≤ 0.02) in TV (0.23 °C), minimum TV (0.18 °C), and maximum TV (0.29 °C) was detected in PP versus IP housed pigs. Similarly, from 0800 to 1900 hours and 2000 to 0700 hours, TV was greater overall (P ≤ 0.01; 0.22 and 0.25 °C, respectively) in PP compared with IP housed pigs. An overall decrease in TS (P = 0.04) was observed in PP (37.39 ± 0.14 °C) compared with IP (37.61 ± 0.14 °C) housed pigs. No RR differences (P > 0.10; 76 ± 4 breaths per minute) were detected with any comparison. While no average daily gain (ADG) and average daily feed intake (ADFI) differences were detected (P > 0.10; 0.74 ± 0.03 kg/d and 2.26 ± 0.08 kg/d, respectively), gain-to-feed ratio (G:F) was decreased (P = 0.02; 6%) in PP compared with IP housed pigs. In summary, pigs located in PP had greater body temperature and reduced G:F despite similarities in TA and RH between all pens.
Comparing quality of reporting between preprints and peer-reviewed articles in the biomedical literature
Authors: Carneiro Clarissa F. D. , Queiroz Victor G. S. , Moulin Thiago C. , Carvalho Carlos A. M. , Haas Clarissa B. , Rayêe Danielle , Henshall David E. , De-Souza Evandro A. , Amorim Felippe E. , Boos Flávia Z. , Guercio Gerson D. , Costa Igor R. , Hajdu Karina L. , van Egmond Lieve , Modrák Martin , Tan Pedro B. , Abdill Richard J. , Burgess Steven J. , Guerra Sylvia F. S. , Bortoluzzi Vanessa T. , Amaral Olavo B.
Published: March 2019

Background

Preprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the reader’s ability to independently interpret data and reproduce findings.

Methods

In this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons between preprints from bioRxiv to their own peer-reviewed versions in journals.

Results

Peer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication.

Conclusions

Our results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions.
N-chlorination mediates protective and immunomodulatory effects of oxidized human plasma proteins
Authors: Ulfig Agnes , Schulz Anton V. , Müller Alexandra , Lupilov Natalie , Leichert Lars I.
Published: March 2019

Hypochlorous acid (HOCl), a powerful antimicrobial oxidant, is produced by neutrophils to fight infections. Here we show thatN-chlorination, induced by HOCl concentrations encountered at sites of inflammation, converts blood plasma proteins into chaperone-like holdases that protect other proteins from aggregation. This chaperone-like conversion was reversible by antioxidants and was abrogated by prior methylation of basic amino acids. Furthermore, reversibleN-chlorination of basic amino acid side chains is the major factor that converts plasma proteins into efficient activators of immune cells. Finally, HOCl-modified serum albumin was found to act as a pro-survival molecule that protects neutrophils from cell death induced by highly immunogenic foreign antigens. We propose that activation and enhanced persistence of neutrophils mediated by HOCl-modified plasma proteins, resulting in the increased and prolonged generation of ROS, including HOCl, constitutes a potentially detrimental positive feedback loop that can only be attenuated through the reversible nature of the modification involved.
tbiExtractor: A framework for extracting traumatic brain injury common data elements from radiology reports
Authors: Mahan Margaret , Rafter Daniel , Casey Hannah , Engelking Marta , Abdallah Tessneem , Truwit Charles , Oswood Mark , Samadani Uzma
Published: March 2019

Objective

The manual extraction of valuable data from electronic medical records is cumbersome, error-prone, and inconsistent. By automating extraction in conjunction with standardized terminology, the quality and consistency of data utilized for research and clinical purposes would be substantially improved. Here, we set out to develop and validate a framework to extract pertinent clinical conditions for traumatic brain injury (TBI) from computed tomography (CT) reports.

Materials and Methods

We developed tbiExtractor, which extends pyConTextNLP, a regular expression algorithm using negation detection and contextual features, to create a framework for extracting TBI common data elements from radiology reports. The algorithm inputs radiology reports and outputs a structured summary containing 27 clinical findings with their respective annotations. Development and validation of the algorithm was completed using two physician annotators as the gold standard.

Results

tbiExtractor displayed high sensitivity (0.92-0.94) and specificity (0.99) when compared to the gold standard. The algorithm also demonstrated a high equivalence (94.6%) with the annotators. A majority of clinical findings (85%) had minimal errors (F1 Score ≥ 0.80). When compared to annotators, tbiExtractor extracted information in significantly less time (0.3 sec vs 1.7 min per report).

Discussion and Conclusion

tbiExtractor is a validated algorithm for extraction of TBI common data elements from radiology reports. This automation reduces the time spent to extract structured data and improves the consistency of data extracted. Lastly, tbiExtractor can be used to stratify subjects into groups based on visible damage by partitioning the annotations of the pertinent clinical conditions on a radiology report.
Integrin-dependent YAP signaling requires LAMTOR1 mediated delivery of Src to the plasma membrane
Authors: Block Marc R. , Brunner Molly , Ziegelmeyer Théo , Lallemand Dominique , Pezet Mylène , Chevalier Genevieve , Rondé Philippe , Wehrle-Haller Bernhard , Bouvard Daniel
Published: March 2019

YAP signaling has emerged as an important signaling pathway involved in several normal and pathological processes. While main upstream effectors regulating its activity have been extensively studied, the interplay with other cellular processes has been far less analyzed. Here, we identified the LAMTOR complex as a new important regulator of YAP signaling. We uncovered that p18/LAMTOR1 is required for the recycling of Src on late endosomes to the cell periphery, and consequently to activate a signaling cascade that eventually controls YAP nuclear shuttling. Moreover, p18/LAMTOR1 positives late endosomes distribution is controlled by β1 integrins, extracellular matrix stiffness and cell contractility. This likely relies on the targeting of microtubules to β1 positive focal adhesion via ILK. Altogether our findings identify the late endosomal recycling pathway as a major regulator of YAP.
Cellular correlates of cortical thinning throughout the lifespan
Authors: Vidal-Pineiro D. , Parker N. , Shin J. , French L. , Grydeland H. , Jackowski AP. , Mowinckel AM. , Patel Y. , Pausova Z. , Salum G. , Sørensen Ø. , Walhovd KB , Paus T. , Fjell AM ,   for the Alzheimer’s Disease Neuroimaging Initiative, for the Australian Imaging Biomarkers,   Lifestyle flagship study of ageing
Published: March 2019

Cortical thinning occurs throughout the entire life and extends to late-life neurodegeneration, yet the neurobiological substrates are poorly understood. Here, we used a virtual-histology technique and gene expression data from the Allen Human Brain Atlas to compare the regional profiles of longitudinal cortical thinning through life (4004 MRIs) with those of gene expression for several neuronal and non-neuronal cell types. The results were replicated in three independent longitudinal datasets. We found that inter-regional profiles of cortical thinning related to expression profiles for marker genes of CA1 pyramidal cells, astrocytes and microglia during development and in aging. During the two stages of life, the relationships went in opposite directions: greater gene expression related to less thinning in development and vice versa in aging. The association between cortical thinning and cell-specific gene expression was also present in mild cognitive impairment and Alzheimer’s Disease. These findings suggest a role of astrocytes and microglia in promoting and supporting neuronal growth and dendritic structures through life that affects cortical thickness during development, aging, and neurodegeneration. Overall, the findings contribute to our understanding of the neurobiology underlying variations in MRI-derived estimates of cortical thinning through life and late-life disease.
Nanodiamonds enable adaptive-optics enhanced, super-resolution, two-photon excitation microscopy
Authors: Johnstone Graeme E. , Cairns Gemma S. , Patton Brian R.
Published: March 2019

Particles of diamond in the 5 to 100 nm size range, known as nanodiamond, have shown promise as robust fluorophores for optical imaging. We demonstrate here that, due to their photo-stability, they are not only suitable for two-photon imaging, but they allow significant resolution enhancement when combined with computational super-resolution techniques. We observe a resolution of 42.5 nm when processing two-photon images with the Super-Resolution Radial Fluctuations algorithm. We show manipulation of the point-spread function of the microscope using adaptive optics. This demonstrates how the photostability of nanodiamond can also be of use when characterising adaptive optics technologies or testing the resilience of super-resolution or aberration correction algorithms.
Anchoring of actin to the plasma membrane enables tension production in the fission yeast cytokinetic ring
Authors: Wang Shuyuan , O’Shaughnessy Ben
Published: March 2019

The cytokinetic ring generates tensile force that drives cell division, but how tension emerges from the relatively disordered ring organization remains unclear. Long ago a muscle-like sliding filament mechanism was proposed, but evidence for sarcomeric order is lacking. Here we present quantitative evidence that in fission yeast ring tension originates from barbed-end anchoring of actin filaments to the plasma membrane, providing resistance to myosin forces which enables filaments to develop tension. The role of anchoring was highlighted by experiments on isolated fission yeast rings, where sections of ring unanchored from the membrane and shortened ~30-fold faster than normal [Mishra M., et al. (2013)Nat Cell Biol15(7):853-859]. The dramatically elevated constriction rates are unexplained. Here we present a molecularly explicit simulation of constricting partially anchored rings as studied in these experiments. Simulations accurately reproduced the experimental constriction rates, and showed that following anchor release a segment becomes tensionless and shortens via a novel non-contractile reeling-in mechanism at about the load-free myosin-II velocity. The ends are reeled in by barbed-end-anchored actin filaments in adjacent segments. Other actin anchoring schemes failed to constrict rings. Our results quantitatively support a specific organization and anchoring scheme that generates tension in the cytokinetic ring.
A cullin-RING ubiquitin ligase promotes thermotolerance as part of the Intracellular Pathogen Response in C. elegans
Authors: Panek Johan , Gang Spencer S. , Reddy Kirthi C. , Luallen Robert J. , Fulzele Amitkumar , Bennett Eric J. , Troemel Emily R.
Published: March 2019

Intracellular pathogen infection leads to proteotoxic stress in host organisms. Previously we described a physiological program in the nematode C. elegans called the Intracellular Pathogen Response (IPR), which promotes resistance to proteotoxic stress and appears to be distinct from canonical proteostasis pathways. The IPR is controlled by PALS-22 and PALS-25, proteins of unknown biochemical function, which regulate expression of genes induced by natural intracellular pathogens. We previously showed that PALS-22 and PALS-25 regulate the mRNA expression of the predicted ubiquitin ligase component cullin cul-6, which promotes thermotolerance in pals-22 mutants. However, it was unclear whether CUL-6 acted alone, or together with other ubiquitin ligase components. Here we use co-immunoprecipitation studies paired with genetic analysis to define the cullin-RING ligase components that act together with CUL-6 to promote thermotolerance. First, we identify a previously uncharacterized RING domain protein in the TRIM family we named RCS-1, which acts as a core component with CUL-6 to promote thermotolerance. Next, we show that the Skp-related proteins SKR-3, SKR-4 and SKR-5 act redundantly to promote thermotolerance with CUL-6. Finally, we screened F-box proteins that co-immunoprecipitate with CUL-6 and find that FBXA-158 promotes thermotolerance. In summary, we have defined the three core components and an F-box adaptor of a cullin-RING ligase complex that promotes thermotolerance as part of the IPR in C. elegans, which adds to our understanding of how organisms cope with proteotoxic stress.

Significance Statement

Intracellular pathogen infection in the nematode Caenorhabditis elegans induces a robust transcriptional response as the host copes with infection. This response program includes several ubiquitin ligase components that are predicted to function in protein quality control. In this study, we show that these infection-induced ubiquitin ligase components form a protein complex that promotes increased tolerance of acute heat stress, an indicator of improved protein homeostasis capacity. These findings show that maintaining protein homeostasis may be a critical component of a multifaceted approach allowing the host to deal with stress caused by intracellular infection.