bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraoperative 3D Hologram Support With Mixed Reality Techniques in Liver Surgery
Authors: Saito Yu , Sugimoto Maki , Imura Satoru , Morine Yuji , Ikemoto Tetsuya , Iwahashi Shuichi , Yamada Shinichiro , Shimada Mitsuo
Published: August 2019

Objective:

The aim of this study was to investigate the potential of an intraoperative 3D hologram, which was a computer graphics model liver, with mixed reality techniques in liver surgery.

Summary Background Data:

The merits for the application of a hologram for surgical support are: 1) no sterilized display monitor; 2) better spatial awareness; and 3) 3D images shared by all the surgeons.

Methods:

3D polygon data using preoperative computed tomography data was installed into head mount displays, HoloLens (Microsoft Corporation, Redmond, WA).

Results:

In a Wi-Fi-enabled operative room, several surgeons wearing HoloLens succeeded in sharing the same hologram and moving that hologram from respective operators’ angles by means of easy gesture-handling without any monitors. The intraoperative hologram contributed to better imagination of tumor locations, and for determining the parenchymal dissection line in the hepatectomy for the patients with more than 20 multiple colo-rectal liver metastases. In another case, the hologram enabled a safe Gliisonean pedicle approach for hepato-cellular carcinoma with a hilar anatomical anomaly. Surgeons could easily compare the real patient's anatomy and that of the hologram just before the hepatic hilar procedure.

Conclusions:

This initial experience suggested that an intraoperative hologram with mixed reality techniques contributed to “last-minute simulation,” not for “navigation.” The intraoperative hologram might be a new next-generation operation-supportive tool in terms of spatial awareness, sharing, and simplicity.
Do the 2018 Leapfrog Group Minimal Hospital and Surgeon Volume Thresholds for Esophagectomy Favor Specific Patient Demographics?
Authors: Clark James M. , Cooke David T. , Hashimi Habiba , Chin David , Utter Garth H. , Brown Lisa M. , Nuño Miriam
Published: August 2019

Objective:

We examine how esophagectomy volume thresholds reflect outcomes relative to patient characteristics.

Summary Background Data:

Esophagectomy outcomes are associated with surgeon and hospital operative volumes, leading the Leapfrog Group to recommend minimum annual volume thresholds of 7 and 20 respectively.

Methods:

Patients undergoing esophagectomy for cancer were identified from the 2007–2013 New York and Florida Healthcare Cost and Utilization Project's State Inpatient Databases. Logit models adjusted for patient characteristics evaluated in-hospital mortality, complications, and prolonged length of stay (PLOS). Median surgeon and hospital volumes were compared between young-healthy (age 18–57, Elixhauser Comorbidity Index [ECI] <2) and older-sick patients (age ≥71, ECI >4).

Results:

Of 4330 esophagectomy patients, 3515 (81%) were male, median age was 64 (interquartile range 58–71), and mortality was 4.0%. Patients treated by both low-volume surgeons and hospitals had the greatest mortality risk (5.0%), except in the case of older-sick patients mortality was highest at high-volume hospitals with high-volume surgeons (12%). For mortality <1%, annual hospital and surgeon volumes needed were 23 and 8, respectively; mortality rose to 4.2% when volumes dropped to the Leapfrog thresholds of 20 and 7, respectively. Complication rose from 53% to 63% when hospital and surgeon volumes decreased from 28 and 10 to 19 and 7, respectively. PLOS rose from 19% to 27% when annual hospital and surgeon volumes decreased from 27 and 8 to 20 and 7, respectively.

Conclusions:

Current Leapfrog Group esophagectomy volume guidelines may not predict optimal outcomes for all patients, especially at extremes of age and comorbidities.
Nationwide Study of Ruptured Abdominal Aortic Aneurysms During Twenty Years (1994–2013)
Authors: Gunnarsson Kim , Wanhainen Anders , Björck Martin , Djavani-Gidlund Khatereh , Mani Kevin
Published: August 2019

Objective:

To analyze the epidemiology of ruptured abdominal aortic aneurysms (RAAA) in Sweden over 20 years, and assess the effect of endovascular repair (EVAR) on surgical treatment rate and outcome.

Methods:

All Swedish citizens >50 years with RAAA 1994 to 2013 were extracted from 3 national (Cause of Death, Patient, and Vascular Surgical) registries. Incidence, proportion repaired, surgical techniques, and 90-day mortality were assessed based on sex and age groups, with regression analysis.

Results:

18,726 individuals with RAAA were identified, 74.0% men. The incidence of RAAA decreased from 33.1/100,000: 1994 to 21.3/100,000: 2013 (relative change −35.6%, P < 0.001). The proportion of men with RAAA undergoing repair was 44.5%: 1994–1998, 49.7%: 2009–2013 (+11.7%, P < 0.001). In women, 22.3% were repaired in 1994–1998, versus 28.2%: 2009–2013 (+26.4%, P < 0.001). The proportion undergoing repair increased in octogenarians (men: +44.3%, P < 0.001; women +49.3%, P = 0.001). EVAR increased from 0% initially to 42.3% in men and 41.2% in women 2013. Overall, mortality rate among all individuals with RAAA decreased, men 75.8%: 1994–1998, 64.8%: 2009–2013 (−14.5%, P < 0.001); women 88.5%: 1994–1998, 82.2%: 2009–2013 (−7.1%, P < 0.001). Among those who underwent repair, mortality was 47.0% in men: 1994–1998, 31.8%: 2009–2013 (−32.3%, P < 0.001); women 51.8%: 1994–1998, 41.4%: 2009–2013 (−20.1%, P = 0.010).

Conclusion:

RAAA mortality among men decreased, mainly attributed to falling incidence of RAAA. The mortality was further reduced by more patients being offered repair, increasingly often with EVAR, and improved survival after repair. Incidence of rupture remained unchanged among women, who had higher RAAA mortality. Focused efforts to reduce RAAA mortality among women are warranted.
Significance of Examined Lymph Node Number in Accurate Staging and Long-term Survival in Resected Stage I–II Pancreatic Cancer—More is Better? A Large International Population-based Cohort Study
Authors: Huang Lei , Jansen Lina , Balavarca Yesilda , van der Geest Lydia , Lemmens Valery , Koerkamp Bas Groot , van Santvoort Hjalmar C. , Grützmann Robert , Besselink Marc G. , Schrotz-King Petra , Brenner Hermann
Published: August 2019

Objective:

This large international cohort study aimed to investigate the associations of examined lymph node (ELN) number with accurate staging and long-term survival in pancreatic adenocarcinoma (PaC) and to robustly determine the minimal and optimal ELN thresholds.

Summary Background Data:

ELN number is an important quality metric in cancer care. The recommended minimal ELN number in PaC to accurately stage cancer varies greatly across guidelines, and the optimal number especially to adequately stratify patient survival has not yet been established.

Methods:

Population-based data on patients with stage I to II PaC resected in 2003 to 2015 from the US Surveillance, Epidemiology, and End Results (SEER)-18 Program and Netherlands National Cancer Registry (NCR) were analyzed. Associations of ELN number with stage migration and survival were evaluated using multivariable-adjusted logistic and Cox regression models, respectively. The series of odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival with more ELNs were fitted using a LOWESS smoother, and structural breakpoints were determined by Chow test.

Results:

Overall 16,241 patients were analyzed. With increasing ELN number, both cohorts exhibited significant proportional increases from nodenegative to node-positive disease [OR
SEER-18 = 1.05, 95% confidence interval (CI) = 1.04–1.05; ORNCR = 1.10, 95% CI = 1.08–1.12] and serial improvements in survival (HR
SEER-18 = 0.98, 95% CI = 0.98–0.99; HRNCR = 0.98, 95% CI = 0.97–0.99) per additional ELN after controlling for confounders. Associations for stage migration and survival remained significant in most stratifications by patient, tumor, and treatment factors. Cut-point analyses suggested a minimal threshold ELN number of 11 and an optimal number of 19, which were validated both internally in the derivative US cohort and externally in the Dutch cohort with the ability to well discriminate different probabilities of both survival and stage migration.

Conclusions:

In stage I to II PaC, more ELNs are associated with more precise nodal staging, which might largely explain the survival association. Our observational study does not suggest causality, and does not encourage more extended lymphadenectomy before further randomized evidence is obtained. Our results robustly conclude 11 ELNs as the minimal and suggest 19 ELNs as the optimal cut-points, for evaluating quality of lymph node examination and possibly for stratifying postoperative prognosis.
Low-pressure Pneumoperitoneum in Laparoscopic Cholecystectomy: A Randomized Controlled Trial
Authors: Neogi Probal , Kumar Pankaj , Kumar Shritosh
Published: August 2019

Background/Purpose:

To compare the changes in hepatic enzymes and comfort level of the surgeon in low-pressure pneumoperitoneum laparoscopic cholecystectomy (LPPLC, 7 mm Hg) with that of normal pressure pneumoperitoneum laparoscopic cholecystectomy (NPPLC, 14 mm Hg).

Methods:

Eighty-two patients were randomly divided into 2 groups (LPPLC and NPPLC). Serum levels of bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, alkaline phosphatase, and lactate dehydrogenase were measured before the operation, at the time of reversal from anesthesia, 24 hours after the operation, and on day 7. Serious adverse events, intra-operative complications, surgeon’s comfort level of dissection, operative time, conversion rates to an open procedure, or normal pressure pneumoperitoneum were recorded.

Results:

Of the 41 patients randomized for LPPLC, 8 patients were converted to NPPLC due to difficulty in dissection and 1 converted to open in each group. There was statistically significant fall in mean serum bilirubin level in both the groups in the immediate postoperative period (P<0.05). Statistically significant increase in its level was observed after 24 hours in the NPPLC group only (P<0.05). Levels of mean serum serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, and lactate dehydrogenase increased significantly (P<0.05) in immediate postoperative period and a further increase was observed after 24 hours (P<0.05) in the NPPLC group only. The comfort level of surgeon was found to be significantly better in the NPPLC group.

Conclusions:

LPPLC is a safe procedure, especially in the hands of an experienced surgeon with clinically insignificant systemic effects. But the comfort level of surgeon is better in normal pressure when compared with low pressure. In patients with deranged hepatic functions undergoing advanced laparoscopic procedures, it is advisable to start the surgery with low-pressure pneumoperitoneum. Pressure may be escalated further as per the surgeon’s comfort.
Selective nonoperative management of renal gunshot wounds
Authors: Schellenberg Morgan , Benjamin Elizabeth , Piccinini Alice , Inaba Kenji , Demetriades Demetrios
Published: August 2019

BACKGROUND

Selective nonoperative management (SNOM) of blunt kidney injuries has been the standard of care for decades. However, the role of SNOM after renal gunshot wounds (GSWs) remains unclear. The purpose of this study was to assess the safety and outcomes of SNOM of renal GSWs at a national level.

METHODS

The National Trauma Data Bank was queried for patients who sustained a GSW to the kidney (January 2007 to December 2014). Patients with emergency department death, transfer, nonsurvivable (Abbreviated Injury Scale score = 6) injuries, absent vitals on arrival, associated hollow viscus or major abdominal vascular injury, or missing procedure/discharge data were excluded. Study groups were defined according to management strategy, with operative management (OM) defined as laparotomy 4 hours or less from admission and SNOM defined by the lack of laparotomy 4 hours or less from admission. Demographics, injury data, and outcomes (mortality, complications, need for nephrectomy, failure of SNOM [defined as laparotomy 5–72 hours after admission], and hospital length of stay [LOS]) were collected. Logistic regression compared outcomes between SNOM and OM.

RESULTS

Over the study period, 1,329 patients met inclusion and exclusion criteria. Of these, 459 (34.5%) underwent SNOM (38.6% of American Association for the Surgery of Trauma kidney injury grades I–II, 39.4% of grade III, 24.0% of grade IV, and 5.2% of grade V). SNOM was associated with significantly shorter hospital LOS (6 days vs. 9 days, p < 0.001). Failure of SNOM occurred in 10.2%. Logistic regression showed no association between SNOM and mortality (odds ratio [OR], 0.614, p = 0.244). However, SNOM was independently associated with fewer complications (OR, 0.711; p = 0.008) and a reduction in need for nephrectomy (OR, 0.056; p < 0.001).

CONCLUSION

SNOM of GSWs to the kidney has become a common practice in the United States. It is safe and has a high success rate, even in severe kidney injuries. It decreases hospital LOS and is independently associated with fewer complications and reduced need for nephrectomy.

LEVEL OF EVIDENCE

Therapeutic/Care Management, level IV.
Delayed interhospital transfer of critically ill patients with surgical sepsis
Authors: Loftus Tyler J. , Wu Quran , Wang Zhongkai , Lysak Nicholas , Moore Frederick A. , Bihorac Azra , Efron Philip A. , Mohr Alicia M. , Brakenridge Scott C.
Published: August 2019

BACKGROUND

Suboptimal triage of critically ill patients with surgical sepsis may contribute to adverse outcomes. Patients transferred to a tertiary care center after spending 24 hours or longer at an outside facility were compared with patients who had early triage to a tertiary care center with the null hypothesis that management parameters and outcomes would be similar between groups.

METHODS

This prospective observational cohort study included 308 patients treated for surgical sepsis in a surgical intensive care unit at a tertiary care center. Patients transferred after spending more than 24 hours at an outside facility (n = 69) were compared with patients who were directly admitted or transferred within 24 hours (n = 239). Patient characteristics, management parameters, and outcomes were compared between groups. This study was registered at ClinicalTrials.gov (NCT02276066).

RESULTS

Average outside facility length of stay in the delayed transfer group was 43 hours. Delayed transfer patients had higher sequential organ failure assessment (7 vs. 5, p = 0.003) and APACHE II scores (19 vs. 16, p = 0.007) on admission. The interval between admission and source control was significantly longer in the delayed transfer group (12.1 hours vs. 1.0 hours, p = 0.009). The incidence of nosocomial infection was significantly higher in the delayed transfer group (41% vs. 23%, p = 0.005). Delayed transfer was independently associated with a 10-day increase in hospital length of stay. Delayed transfer patients were less likely to be discharged home (22% vs. 59%, p < 0.001) and suffered twofold higher in-hospital mortality (14.5% vs. 7.1%, p = 0.056).

CONCLUSION

Patients with surgical sepsis who spent more than 24 hours at an outside facility prior to transfer had greater initial illness severity, longer intervals between admission and source control, and more nosocomial infections compared with patients who had early triage to a tertiary care center.

LEVEL OF EVIDENCE

Care management/therapeutic, Level IV; Epidemiologic/prognostic, Level III.
The Israel Defense Forces experience with freeze-dried plasma for the resuscitation of traumatized pediatric patients
Authors: Nadler Roy , Mozer-Glassberg Yael , Gaines Barbara , Glassberg Elon , Chen Jacob
Published: August 2019

BACKGROUND

With the growing recognition of the disadvantages of crystalloid- and colloid-based resuscitation and the advantages of using blood products as the preferred resuscitation fluid, the Israel Defense Forces Medical Corps (IDF-MC) adopted plasma as the primary volume resuscitation regimen in 2013. While data are accumulating for prehospital plasma transfusion, little to no data exist regarding using plasma as a prehospital resuscitation fluid for traumatized pediatric patients.

METHODS

All patients treated by the IDF-MC personnel are recorded in the IDF Trauma Registry, a unique prehospital trauma registry. All patients treated by the IDF advanced life support providers with FDP at the point of injury between April 2013 and June 2018 who were younger than 18 years at the time of injury were included.

RESULTS

Six hundred seventy-nine children were treated by IDF medical providers, of whom 33 (5%) were identified in the IDF Trauma Registry as having received FDP at the point of injury. Most patients (80%) were treated for penetrating injuries. Most patients received one plasma unit. Fifty-four percent of the patients were also treated by Tranexamic Acid (TXA) and 48% were transfused with crystalloids. In 33% of patients, additional life-saving interventions were performed.

CONCLUSION

While the ideal resuscitation fluid for the pediatric population remains to be determined, it seems reasonable to pursue a similar approach to that of applied that for adults. In the IDF-MC, the resuscitation fluid of choice for trauma patients in hemorrhagic shock is freeze-dried plasma transfused at the point of injury. The current study demonstrates the feasibility of FDP administration in the prehospital scenario for injured children and further supports the growing confidence in the use of FDP for the treatment of pediatric trauma patients.

LEVEL OF EVIDENCE

Retrospective descriptive study, level IV.
Ketamine infusion for pain control in elderly patients with multiple rib fractures: Results of a randomized controlled trial
Authors: Kugler Nathan W. , Carver Thomas W. , Juul Janelle , Peppard William J. , Boyle Kelly , Drescher Karin Madsen , Szabo Aniko , Rein Lisa , Somberg Lewis B. , Paul Jasmeet S.
Published: August 2019

BACKGROUND

Rib fractures are associated with increased mortality, particularly in the elderly. While opiate-based pain regimens remain the cornerstone of rib fracture management, issues related to opioids have driven research into alternative analgesics. Adjunctive ketamine use in lieu of opioids continues to increase but little evidence exists to support its efficacy or safety within the elderly trauma population.

METHODS

A prospective, randomized, double-blind placebo-controlled trial of elderly patients (age, ≥65 years) with three or more rib fractures admitted to a Level I trauma center was conducted. Exclusion criteria included Glasgow Coma Scale score less than 14, and chronic opiate use. Groups were randomized to either low-dose ketamine (LDK) at 2 μg·kg−1·min−1 or an equivalent rate of 0.9% normal saline. The primary outcome was reduction in numeric pain scores (NPS). Secondary outcomes included oral morphine equivalent (OME) utilization, epidural rates, pulmonary complications, and adverse events.

RESULTS

Thirty (50.8%) of 59 were randomized to the experimental arm. Groups were similar in makeup. Low-dose ketamine failed to reduce 24-hour NPS or OME totals. Subgroup analysis of 24 patients with Injury Severity Score greater than 15 demonstrated that LDK was associated with a reduction in OME utilization the first 24-hours (25.6 mg vs. 42.6 mg, p = 0.04) but at no other time points. No difference in other secondary outcomes or adverse events was noted.

CONCLUSION

Low-dose ketamine failed to affect NPS or OME within the overall cohort, but a decrease in OME was observed in those with an Injury Severity Score greater than 15. Additional studies are necessary to confirm whether LDK benefits severely injured elderly patients.

LEVEL OF EVIDENCE

Therapeutic, level I.
The Sequential Clinical Assessment of Respiratory Function (SCARF) score: A dynamic pulmonary physiologic score that predicts adverse outcomes in critically ill rib fracture patients
Authors: Hardin Kimberly S. , Leasia Kiara N. , Haenel James , Moore Ernest E. , Burlew Clay Cothren , Pieracci Fredric M.
Published: August 2019

BACKGROUND

Rib fracture scoring systems are limited by a lack of serial pulmonary physiologic variables. We created the Sequential Clinical Assessment of Respiratory Function (SCARF) score and hypothesized that admission, maximum, and rising scores predict adverse outcomes among critically ill rib fracture patients.

METHODS

Prospective cohort study of rib fracture patients admitted to the surgical intensive care unit (ICU) at a Level I trauma center from August 2017 to June 2018. The SCARF score was developed a priori and validated using the cohort. One point was assigned for: <50% predicted, respiratory rate >20, numeric pain score ≥5, and inadequate cough. Demographics, injury patterns, analgesics, and adverse pulmonary outcomes were abstracted. Performance characteristics of the score were assessed using the receiver operator curve area under the curve.

RESULTS

Three hundred forty scores were available from 100 patients. Median admission and maximum SCARF score was 2 (range 0-4). Likelihood of pneumonia (p = 0.04), high oxygen requirement (p < 0.01), and prolonged ICU length of stay (p < 0.01) were significantly associated with admission and maximum scores. The receiver operator curve area under the curve for the maximum SCARF score for these outcomes were 0.86, 0.76, and 0.79, respectively. In 10 patients, the SCARF score worsened from admission to day 2; these patients demonstrated increased likelihood of pneumonia (p = 0.04) and prolonged ICU length of stay (p = 0.07). Patients who developed complications maintained a SCARF score one point higher throughout ICU stay compared with patients who did not (p = 0.04). The SCARF score was significantly associated with both narcotic (p = 0.03) and locoregional anesthesia (p = 0.03) usage.

CONCLUSION

Admission, maximum, daily, and rising scores were associated with utilization of pain control therapies and development of adverse outcomes. The SCARF score may be used to guide therapies for critically ill rib fracture patients, with a proposed threshold greater than 2.

LEVEL OF EVIDENCE

Prognostic study, level II.
Random forest modeling can predict infectious complications following trauma laparotomy
Authors: Gelbard Rondi B. , Hensman Hannah , Schobel Seth , Khatri Vivek , Tracy Brett M. , Dente Christopher J. , Buchman Timothy , Kirk Allan , Elster Eric
Published: August 2019

BACKGROUND

Identifying clinical and biomarker profiles of trauma patients may facilitate the creation of models that predict postoperative complications. We sought to determine the utility of modeling for predicting severe sepsis (SS) and organ space infections (OSI) following laparotomy for abdominal trauma.

METHODS

Clinical and molecular biomarker data were collected prospectively from patients undergoing exploratory laparotomy for abdominal trauma at a Level I trauma center between 2014 and 2017. Machine learning algorithms were used to develop models predicting SS and OSI. Random forest (RF) was performed, and features were selected using backward elimination. The SS model was trained on 117 records and validated using the leave-one-out method on the remaining 15 records. The OSI model was trained on 113 records and validated on the remaining 19. Models were assessed using areas under the curve.

RESULTS

One hundred thirty-two patients were included (median age, 30 years [23–42 years], 68.9% penetrating injury, median Injury Severity Score of 18 [10–27]). Of these, 10.6% (14 of 132) developed SS and 13.6% (18 of 132) developed OSI. The final RF model resulted in five variables for SS (Penetrating Abdominal Trauma Index, serum epidermal growth factor, monocyte chemoattractant protein-1, interleukin-6, and eotaxin) and four variables for OSI (Penetrating Abdominal Trauma Index, serum epidermal growth factor, monocyte chemoattractant protein-1, and interleukin-8). The RF models predicted SS and OSI with areas under the curve of 0.798 and 0.774, respectively.

CONCLUSION

Random forests with RFE can help identify clinical and biomarker profiles predictive of SS and OSI after trauma laparotomy. Once validated, these models could be used as clinical decision support tools for earlier detection and treatment of infectious complications following injury.

LEVEL OF EVIDENCE

Prognostic, level III.
The Small RNA Repertoire of Small Extracellular Vesicles Isolated From Donor Kidney Preservation Fluid Provides a Source for Biomarker Discovery for Organ Quality and Posttransplantation Graft Function
Authors: Gremmels Hendrik , de Jong Olivier G. , Toorop Raechel J. , Michielsen Laura , van Zuilen Arjan D. , Vlassov Alexander V. , Verhaar Marianne C. , van Balkom Bas W.M.
Published: August 2019

Background.

Delayed graft function (DGF) after kidney transplantation is negatively associated with long-term graft function and survival. Kidney function after transplantation depends on multiple factors, both donor- and recipient-associated. Prediction of posttransplantation graft function would allow timely intervention to optimize patient care and survival. Currently, graft-based predictions can be made based on histological and molecular analyses of 0-hour biopsy samples. However, such analyses are currently not implemented, as biopsy samples represent only a very small portion of the entire graft and are not routinely analyzed in all transplantation centers. Alternatives are thus required.

Methods.

We analyzed whether donor organ preservation fluid contain small extracellular vesicles (sEV) and whether the RNA content of these vesicles could be used as a source for potential biomarkers for posttransplantation kidney function.

Results.

We provide proof of principle that sEVs are present in preservation fluid, which contain RNAs associated with donor origin. Furthermore, sEV micro RNA profiles could be associated with graft function during the first 7 days posttransplantation, but no significant correlation with DGF could be established based on the current dataset.

Conclusions.

Overall, the predictive potential of sEV RNA biomarkers together with relatively easy and noninvasive sample collection and analysis methods could pave the way towards universal screening of donor kidney-associated risk for DGF, optimized patient treatment, and subsequently improved short- and long-term graft function and survival.
Medal: a patient similarity metric using medication prescribing patterns
Authors: Pineda Arturo Lopez , Pourshafeie Armin , Ioannidis Alexander , Leibold Collin McCloskey , Chan Avis , Frankovich Jennifer , Bustamante Carlos D. , Wojcik Genevieve L.
Published: August 2019

Patient similarity offers an exciting potential to improve our understanding of treatment patterns. Medication history is a valuable source of information given the clinical considerations taken during the physician’s prescription process. However, available similarity methods do not consider timeliness of event occurrence in the longitudinal care of patients.

In this observational cohort study, we propose an event alignment algorithm, Medal, which uses a dynamic programming approach for pairwise alignment of medication histories. To test our algorithm, we obtained the medication usage from a cohort of patients with pediatric acute-onset neuropsychiatric syndrome (PANS). After calculating a distance metric with Medal, we compute a hierarchical clustering and explore the most appropriate number of clusters.

We identified four clusters in PANS with distinct medication usage histories, driven primarily by penicillin. We foresee that our algorithm could be used to identify clusters in other syndromes treated with multiple medication regimens.
Rationalising neurosurgical head injury referrals: The development and implementation of the Liverpool Head Injury Tomography Score (Liverpool HITS) for mild traumatic brain injury
Authors: Gillespie Conor SN , Mcleavy Christopher M , Islim Abdurrahman I , Prescott Sarah , McMahon Catherine J
Published: August 2019

Objectives

To develop and implement a radiological scoring system to define a ‘surgically significant’ mild Traumatic Brain Injury (TBI), stratify neurosurgical referrals and improve communication between referral centres and neurosurgical units.

Design

Retrospective single centre case-control analysis of ten continuous months of mild TBI referrals.

Setting

A major tertiary neurosurgery centre in England, UK.

Participants

All neurosurgical referrals with a mild TBI (GCS 13-15) during the period of 1st January to 30th October 2017 were eligible for the study. 1248 patients were identified during the study period, with 1144 being included in the final analysis.

Interventions

All patients’ CT head results from the referring centres were scored retrospectively using the scoring system and stratified according to their mean score, and if they were accepted for transfer to the neurosurgical centre or managed locally.

Main outcome measure

Determine the discriminatory and diagnostic power, sensitivity and specificity of the scoring system for predicting a ‘surgically significant’ mild TBI.

Results

Most patients referred were male (59.4%, N=681), with a mean age of 69 years (SD=21.1). Of the referrals to the neurosurgical centre, 17% (n=195) were accepted for transfer and 83% (n=946) were not accepted. The scoring system was 99% sensitive and 51.9% specific for determining a surgically significant TBI. Diagnostic power of the model was fair with an area under the curve of 0.79 (95% CI 0.76 to 0.82). The score identified 495 (52.2%) patients in ten months of referrals that could have been successfully managed locally without neurosurgical referral if the scoring system was correctly used at the time of injury.

Conclusion

The Liverpool Head Injury Tomography Score (HITS) score is a CT based scoring system that can be used to define a surgically significant mild TBI. The scoring system can be easily used by multiple healthcare professionals, has high sensitivity, will reduce neurosurgical referrals, and could be incorporated into local, regional and national head injury guidance.
The Implementation, Diagnostic Yield and Clinical Outcome of Genetic Testing on an Inpatient Child and Adolescent Psychiatry Service
Authors: Besterman Aaron D. , Sadik Joshua , Enenbach Michael J. , Quintero-Rivera Fabiola ,   UCLA Clinical Genomics Center, DeAntonio Mark , Martinez-Agosto Julian A.
Published: August 2019

Objective

Diagnostic genetic testing is recommended for children with neurodevelopmental disorders (NDDs). However, many children with NDDs do not receive genetic testing. One approach to improve access to genetic services for these patients is to offer testing on the inpatient child and adolescent psychiatry (CAP) service.

Methods

We implemented systematic genetic testing on an inpatient CAP service by providing medical genetics education to CAP fellows. We compared the genetic testing rates pre- and post-education. We compared the diagnostic yield to previously published studies and the demographics of our cohort to inpatients who received genetic testing on other clinical services. We assessed rates of outpatient genetics follow-up post-discharge.

Results

The genetic testing rate on the inpatient CAP service was 1.6% (2/125) before the educational intervention and 10.7% (21/197) afterwards (OR = 0.13, 95% CI = 0.015- 0.58, p = 0.0015). Diagnostic yield for patients on the inpatient service was 4.3% (1/23), lower than previously reported. However, 34.8% (8/23) of patients had variants of unknown significance (VUSs). 39.1% (9/23) of children who received genetic testing while inpatients were underrepresented minorities, compared to 7.7% (1/13) of patients who received genetic testing on other clinical services (OR = 7.35, CI = 0.81-365.00, p = 0.057). 43.5% of patients were lost to outpatient genetics follow-up.

Conclusion

Medical genetics education for fellows on an inpatient CAP service can improve genetic testing rates. Genetic testing for inpatients may primarily identify VUSs instead of well-known NDD risk variants. Genetic testing on the inpatient CAP service may improve access to genetic services for underrepresented minorities, but assuring outpatient follow-up can be challenging.
A gene-diet interaction-based score predicts response to dietary fat in the Women’s Health Initiative
Authors: Westerman Kenneth , Liu Qing , Liu Simin , Parnell Laurence D. , Sebastiani Paola , Jacques Paul , DeMeo Dawn L. , Ordovás José M.
Published: August 2019

While diet response prediction for cardiometabolic risk factors (CRFs) has been demonstrated using single SNPs and main-effect genetic risk scores, little investigation has gone into the development of genome-wide diet response scores. We sought to leverage the multi-study setup of the Women’s Health Initiative cohort to generate and test genetic scores for the response of six CRFs (body mass index, systolic blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and fasting glucose) to dietary fat. A genome-wide interaction study was undertaken for each CRF in women (n ∼ 10000) not participating in the Dietary Modification (DM) trial, which focused on the reduction of dietary fat. Genetic scores based on these analyses were developed using a pruning-and-thresholding approach and tested for the prediction of one-year CRF changes as well as long-term chronic disease development in DM trial participants (n ∼ 5000). One of these genetic scores, for LDL-cholesterol (LDL-C), predicted changes in the associated CRF. This 1760-variant score explained 3.4% of the variance in one-year LDL-C changes in the intervention arm, but was unassociated with changes in the control arm. In contrast, a main-effect genetic risk score for LDL-C was not useful for predicting dietary fat response. Further investigation of this score with respect to downstream disease outcomes revealed suggestive differential associations across DM trial arms, especially with respect to coronary heart disease and stroke subtypes. These results lay the foundation for the combination of many genome-wide gene-diet interactions for diet response prediction while highlighting the need for further research and larger samples in order to achieve robust biomarkers for use in personalized nutrition.
Comparison of risk factors for coronary heart disease morbidity versus mortality
Authors: Batty G. David , Kivimäki Mika , Bell Steven
Published: August 2019

Owing to the often prohibitively high costs of medical examinations, or an absence of infrastructure for linkage of study members to morbidity registries, much aetiological research in the field of cardiovascular research relies on death records. Because they are regarded as being more distal to risk factor assessment than morbidity endpoints, mortality data are generally maligned in this context for seemingly providing less clear insights into aetiology. The relative utility of mortality versus morbidity registries is, however, untested. In a pooling of data from three large cohort studies whose participants had been linked to both death and morbidity registries for coronary heart disease, we related a range of established and emerging risk factors to these two methods of ascertainment. A mean duration of study member surveillance of 10.1 years (mortality) and 9.9 years (morbidity) for a maximum of 20,956 study members (11,868 women) in the analytical sample yielded 289 deaths from coronary heart disease and 770 hospitalisations for this condition. The direction of the age- and sex-adjusted association was the same for 21 of the 24 risk factor– morbidity/mortality combinations. The only marked discordance in effect estimates, such that different conclusions about the association could be drawn, was for social support, total cholesterol, and fruit/vegetable consumption whereby null effects were evident for selected outcomes. In conclusion, variation in disease definition typically did not have an impact on the direction of the association of an array of risk factors for coronary heart disease.
A Transient Intermediate Populated in Prion Folding Leads to Domain Swapping
Authors: Mondal Balaka , Reddy Govardhan
Published: August 2019

Aggregation of misfolded prion proteins causes fatal neurodegenerative disorders in both humans and animals. There is an extensive effort to identify the elusive aggregation-prone conformations (N*) of prions, which are early stage precursors to aggregation. Ve studied temperature and force induced unfolding of the structured C-terminal domain of mouse (moPrP) and human prion proteins (hPrP) using molecular dynamics simulations and coarse-grained protein models. Ve find that these proteins sparsely populate intermediate states bearing the features of N* and readily undergo domain-swapped dimerization by swapping the short β-strands present at the beginning of the C-terminal domain. Structure of the N* state is similar for both moPrP and hPrP, indicating a common pathogenic precursor across diferent species. Interestingly, disease-resistant hPrP (G127V) showed a drastic reduction in the population of N* state further hinting a pathogenic connection to these partially denatured conformations. This study proposes a plausible runaway domain swapping mechanism to describe the onset of prion aggregation.
Evolution of Specialization in Dynamic Fluids
Authors: Uppal Gurdip , Vural Dervis Can
Published: August 2019

Previously we found mechanical factors involving diffusion and fluid shear promote evolution of social behavior in microbial populationsUppal and Vural (2018). Here, we extend this model to study the evolution of specialization using realistic physical simulations of bacteria that secrete two public goods in a dynamic fluid. Through this first principles approach, we find physical factors such as diffusion, flow patterns, and decay rates are as influential as fitness economics in governing the evolution of community structure, to the extent that when mechanical factors are taken into account, (1) Generalist communities can resist becoming specialists, despite the invasion fitness of specialization (2) Generalist and specialists can both resist cheaters despite the invasion fitness of free-riding. (3) Multiple community structures can coexist despite the opposing force of competitive exclusion. Our results emphasize the role of spatial assortment and physical forces on niche partitioning and the evolution of diverse community structures.
deSAMBA: fast and accurate classification of metagenomics long reads with sparse approximate matches
Authors: Li Gaoyang , Liu Bo , Wang Yadong
Published: August 2019

Long read sequencing technologies are promising to metagenomics studies. However, there is still lack of read classification tools to fast and accurately identify the taxonomies of noisy long reads, which is a bottleneck to the use of long read sequencing. Herein, we propose deSAMBA, a tailored long read classification approach that uses a novel sparse approximate match block (SAMB)-based pseudo alignment algorithm. Benchmarks on real datasets demonstrate that deSAMBA enables to simultaneously achieve fast speed and good classification yields, which outperforms state-of-the-art tools and has many potentials to cutting-edge metagenomics studies.

Availability and Implementation

https://github.com/hitbc/deSAMBA.

Supplementary information:
Nucleated transcriptional condensates amplify gene expression
Authors: Wei Ming-Tzo , Chang Yi-Che , Shimobayashi Shunsuke F. , Shin Yongdae , Brangwynne Clifford P.
Published: August 2019

Liquid-liquid phase separation is thought to underly gene transcription, through the condensation of the large-scale nucleolus, or in smaller assemblies known as transcriptional hubs or condensates. However, phase separation has not yet been directly linked with transcriptional output, and our biophysical understanding of transcription dynamics is poor. Here, we utilize an optogenetic approach to control condensation of key FET-family transcriptional regulators, particularly TAF15. We show that amino acid sequence-dependent phase separation of TAF15 is enhanced significantly due to strong nuclear interactions with the C-terminal domain (CTD) of RNA Pol II. Nascent CTD clusters at primed genomic loci lower the energetic barrier for nucleation of TAF15 condensates, which in turn further recruit RNA Pol II to drive transcriptional output. These results suggest a model in which positive feedback between key transcriptional components drives intermittent dynamics of localized phase separation, to amplify gene expression.
Interpretable factor models of single-cell RNA-seq via variational autoencoders
Authors: Svensson Valentine , Pachter Lior
Published: August 2019

Single cell RNA-seq makes possible the investigation of variability in gene expression among cells, and dependence of variation on cell type. Statistical inference methods for such analyses must be scalable, and ideally interpretable. We present an approach based on a modification of a recently published highly scalable variational autoencoder framework that provides interpretability without sacrificing much accuracy. We demonstrate that our approach enables identification of gene programs in massive datasets. Our strategy, namely the learning of factor models with the auto-encoding variational Bayes framework, is not domain specific and may be of interest for other applications.
Entry by multiple picornaviruses is dependent on a pathway that includes TNK2, WASL and NCK1
Authors: Jiang Hongbing , Leung Christian , Tahan Stephen , Wang David
Published: August 2019

Comprehensive knowledge of the host factors required for picornavirus infection would facilitate antiviral development. Here we demonstrate roles for three human genes, TNK2, WASL, and NCK1, in infection by multiple picornaviruses. CRISPR deletion of TNK2, WASL or NCK1 reduced encephalomyocarditis virus (EMCV), coxsackievirus B3 (CVB3), poliovirus and enterovirus D68 infection, and chemical inhibitors of TNK2 and WASL decreased EMCV infection. Reduced EMCV lethality was observed in mice lacking TNK2. TNK2, WASL and NCK1 were important in early stages of the viral lifecycle, and genetic epistasis analysis demonstrated that the three genes function in a common pathway. Mechanistically, reduced internalization of EMCV was observed in TNK2 deficient cells demonstrating that TNK2 functions in EMCV entry. Domain analysis of WASL demonstrated that its actin nucleation activity was necessary to facilitate viral infection. Together, these data support a model wherein TNK2, WASL, and NCK1 comprise a pathway critical for multiple picornaviruses.
Testosterone-mediated behavior shapes the emergent properties of social networks
Authors: Dakin Roslyn , Moore Ignacio T. , Horton Brent M. , Vernasco Ben J. , Ryder T. Brandt
Published: August 2019

Social networks can vary in their organization and dynamics, with implications for ecological and evolutionary processes. Understanding the mechanisms that drive social network dynamics requires integrating individual-level biology with comparisons across multiple social networks.

Testosterone is a key mediator of vertebrate social behavior and can influence how individuals interact with social partners. Although the effects of testosterone on individual behavior are well established, no study has examined whether hormone-mediated behavior can scale up to shape the emergent properties of social networks.

We investigated the relationship between testosterone and social network dynamics in the wire-tailed manakin, a lekking bird species in which male-male social interactions form complex social networks. We used an automated proximity system to longitudinally monitor several leks and we quantified the social network structure at each lek. Our analysis examines three emergent properties of the networks: social specialization (the extent to which a network is partitioned into exclusive partnerships), network stability (the overall persistence of partnerships through time), and behavioral assortment (the tendency for like to associate with like). All three properties are expected to promote the evolution of cooperation. As the predictor, we analyzed the collective testosterone of males within each social network.

Social networks that were composed of high-testosterone dominant males were less specialized, less stable, and had more negative behavioral assortment, after accounting for other factors. These results support our main hypothesis that individual-level hormone physiology can predict group-level network dynamics. We also observed that larger leks with more interacting individuals had more positive behavioral assortment, suggesting that small groups may constrain the processes of homophily and behavior-matching.

Overall, these results provide evidence that hormone-mediated behavior can shape the broader architecture of social groups. Groups with high average testosterone exhibit social network properties that are predicted to impede the evolution of cooperation.
Organization of fast and slow chromatin revealed by single-nucleosome dynamics
Authors: Ashwin S. S. , Nozaki Tadasu , Maeshima Kazuhiro , Sasai Masaki
Published: August 2019

Understanding chromatin organization and dynamics is important since they crucially affect DNA functions. In this study, we investigate chromatin dynamics by statistically analyzing single-nucleosome movement in living human cells. Bi-modal nature of the mean squared displacement distribution of nucleosomes allows for a natural categorization of the nucleosomes as fast and slow. Analyses of the nucleosome-nucleosome correlation functions within these categories along with the density of vibrational modes show that the nucleosomes form dynamically correlated fluid regions, i.e., dynamic domains of fast and slow nucleosomes. Perturbed nucleosome dynamics by global histone acetylation or cohesin inactivation indicate that nucleosome-nucleosome interactions along with tethering of chromatin chains organize nucleosomes into fast and slow dynamic domains. A simple polymer model is introduced, which shows the consistency of this dynamic domain picture. Statistical analyses of single-nucleosome movement provide rich information on how chromatin is dynamically organized in a fluid manner in living cells.

Significan Statement

Recent live cell imaging has revealed that chromatin is not a static, rigid structure but is dynamically fluctuating in cells. We study chromatin motion by using single-nucleosome tracking data in living human cells. The distribution of single-nucleosome movement shows a distinct two-peak feature: fast and slow fractions. Nucleosome movement is investigated using statistical analyses and a polymer model to elucidate the mechanism of dynamic organization of fast and slow chromatin.