bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetically-edited induced pluripotent stem cells derived from HIV-1-infected patients on therapy can give rise to immune cells resistant to HIV-1 infection
Authors: Teque Fernando , Ye Lin , Xie Fei , Wang Jiaming , Morvan Maelig G. , Kan Yuet Wai , Levy Jay A. 
Published: April 2020

Objective:
To assess the in-vitro CCR5---tropic and CXCR4---tropic HIV---1 infectivity of immune cells, particularly macrophages, derived from CCR5 gene---edited induced pluripotent stem cells (iPSCs) obtained from the peripheral blood mononuclear cells (PBMC) of HIV---infected patients on antiretroviral therapy (ART).

Design:
PBMC were obtained from six patients who had been HIV---infected for over 20 years and were on ART for 1---12 years prior to this study.

Methods:
The PBMC were derived into iPSCs and genetically edited with TALENs or CRISPR---cas9 endonucleases combined with PiggyBac technology to introduce the naturally occurring 32---bp deletion to the CCR5 gene. These iPSCs were differentiated into macrophages, and subsequently challenged with CCR5---tropic or CCR5/CXCR4 dual--- tropic HIV---1 strains. iPSC derivation, gene editing and immune cell differentiation were done in feeder---free, xeno---free in-vitro conditions.

Results:
Multiple unedited (wild---type) and CCR5 gene---edited (mutant) iPSCs were derived from patients’ PBMC. When differentiated into immune cells and HIV---1 challenged, mutant iPSC lines were resistant to CCR5---tropic and to some extent to CCR5/CXCR4 dual---tropic HIV---1 infection when compared to wild---type iPSC lines.

Conclusion:
Our study demonstrates that iPSC---derived, gene---edited immune cells are resistant to distinct HIV---1 strains. These findings have important implications for both in-vitro stem cell development and therapeutic approaches to cure HIV infection.
Application of Transparent Cap-assisted Choledochoscopy in Endoscopic Gallbladder-preserving Surgery
Authors: Jian Wei , Song Yan-zhou , Xiang Qing-feng , Tian Heng-yu , Xie Zhuo-zhao , Yang Jun-bo , Zhang Yi-ming , Zhang Rui-kun , Liu Jia-lin 
Published: April 2020

Background:
The gold standard treatment for cholecystolithiasis is laparoscopic cholecystectomy. However, the complications of cholecystectomy have led to adoption of gallbladder-preserving surgery. The study was to investigate significance of transparent cap-assisted choledochoscopy in gallbladder-preserving surgery.

Materials and Methods:
This is a retrospective study of patients who underwent gallbladder-preserving surgery by laparoscopic choledochoscopy along with choledochoscopy with or without a transparent cap from January 2018 to September 2018 in our hospital. The differences in the duration of gallbladder exploration, surgical complications, adverse events, and the recurrence of stones within 6 months after surgery were compared between 2 groups.

Results:
Fifty patients underwent laparoscopic choledochoscopy along with choledochoscopy without transparent cap (Group A), while 50 patients underwent laparoscopic along with transparent cap-assisted choledochoscopy (Group B). Gallbladder exploration time was 27.96±12.24 minutes in Group A, and 12.04±6.01 minutes in Group B. One case had stone recurrence within 6 months in Group B, while 8 cases had stone recurrence in group A.

Conclusions:
Comparing with laparoscope combined with choledochoscopy, transparent cap-assisted choledochoscopy has advantages in gallbladder-preserving surgery.
Prehospital definitive airway is not associated with improved survival in trauma patients
Authors: Tsur Avishai M. , Nadler Roy , Tsur Nir , Sorkin Alex , Bader Tarif , Benov Avi , Glassberg Elon , Chen Jacob 
Published: April 2020

BACKGROUND
The American College of Surgeons and the National Association of Emergency Medical Technicians advise securing a definitive airway if there is any doubt about the trauma patient's ability to maintain airway integrity. The objective of this study was to investigate the association between a success in securing a definitive airway in the prehospital setting and survival among trauma patients, in which the provider deemed a definitive airway was necessary.

METHODS
The study included all trauma patients recorded in the Israel Defense Forces Trauma Registry between the years 2006 and 2018 for whom a prehospital attempt of securing a definitive airway was documented. The successful definitive airway group was defined by explicit documentation of success in either endotracheal intubation or cricothyrotomy. Logistic regression was performed to determine the association between success in securing a definitive airway and survival.

RESULTS
A total of 566 (3.6%) trauma patients underwent attempts to secure a definitive airway (successful in 425 patients and unsuccessful in 141). Prehospital survival rates were similar (77.6% vs. 78.0%, p = 0.928) between the groups. Whether the definitive airway was successful did not affect the rates of prehospital survival, neither before (odds ratio, 0.98; 95% confidence interval, 0.61–1.54) nor after adjustment for the other factors (odds ratio, 0.91; 95% confidence interval, 0.55–1.46).

CONCLUSION
This study was unable to find an association between a successful definitive airway in the prehospital setting and survival, even after adjustment for injury characteristics and in multiple models. Furthermore, survival rates were high among trauma patients in which the provider deemed a definitive airway as necessary yet failed in securing one. These results suggest that the liberal use of these invasive airway procedures in the prehospital setting should be reconsidered.

LEVEL OF EVIDENCE
Retrospective study, lebel III.
Blood product needs and transfusion timelines for the multisite massive Paris 2015 terrorist attack: A retrospective analysis
Authors: Martinez Thibault , François Anne , Pouget Thomas , Carli Pierre , Lapostolle Frédéric , Gauss Tobias , Hamada Sophie Rym , Langlois Matthieu , Yordanov Youri , Féral-Pierssens Anne-Laure , Woloch Alexandre , Ogereau Carl , Gayat Etienne , Attias Arié , Pateron Dominique , Castier Yves , Ludes Bertrand , Dolla Emmanuelle , Tourtier Jean-Pierre , Riou Bruno , Raux Mathieu , Ausset Sylvain ,   TRAUMABASE group
Published: April 2020

OBJECTIVE
Hemorrhage is the leading cause of death after terrorist attack, and the immediacy of labile blood product (LBP) administration has a decisive impact on patients' outcome. The main objective of this study was to evaluate the transfusion patterns of the Paris terrorist attack victims, November 13, 2015.

METHODS
We performed a retrospective analysis including all casualties admitted to hospital, aiming to describe the transfusion patterns from admission to the first week after the attack.

RESULTS
Sixty-eight of 337 admitted patients were transfused. More than three quarters of blood products were consumed in the initial phase (until November 14, 11:59 pm), where 282 packed red blood cell (pRBC) units were transfused along with 201 plasma and 25 platelet units, to 55 patients (16% of casualties). Almost 40% of these LBPs (134 pRBC, 73 plasma, 8 platelet units) were transfused within the first 6 hours after the attack. These early transfusions were massive transfusion (MT) for 20 (6%) of 337 patients, and the average plasma/red blood cell ratio was 0.8 for MT patients who received 366 (72%) of 508 LBPs.
The median time from admission to pRBC transfusion was 57 (25–108) minutes and 208 (52–430) minutes for MT and non-MT patients, respectively. These same time intervals were 119 (66–202) minutes and 222 (87–381) minutes for plasma and 225 (131–289) minutes and 198 (167–230) minutes for platelets.

CONCLUSION
Our data suggest that improving transfusion procedures in mass casualty setting should rely more on shortening the time to bring LBP to the bedside than in increasing the stockpile.

LEVEL OF EVIDENCE
Epidemiological study, Therapeutic IV.
Establishing an enduring Military Trauma Mortality Review: Misconceptions and lessons learned
Authors: Janak Jud C. , Mazuchowski Edward L. , Kotwal Russ S. , Howard Jeffrey T. , Stockinger Zsolt T. , Gurney Jennifer M. , Shackelford Stacy A. 
Published: April 2020

ABSTRACT
Under direction from the Defense Health Agency, subject matter experts (SMEs) from the Joint Trauma System, Armed Forces Medical Examiner System, and civilian sector established the Military Trauma Mortality Review process. To establish the most empirically robust process, these SMEs used both qualitative and quantitative methods published in a series of peer-reviewed articles over the last 3 years. Most recently, the Military Mortality Review process was implemented for the first time on all battle-injured service members attached to the United States Special Operations Command from 2001 to 2018. The current Military Mortality Review process builds on the strengths and limitations of important previous work from both the military and civilian sector. To prospectively improve the trauma care system and drive preventable death to the lowest level possible, we present the main misconceptions and lessons learned from our 3-year effort to establish a reliable and sustainable Military Trauma Mortality Review process. These lessons include the following: (1) requirement to use standardized and appropriate lexicon, definitions, and criteria; (2) requirement to use a combination of objective injury scoring systems, forensic information, and thorough SME case review to make injury survivability and death preventability determinations; (3) requirement to use nonmedical information to make reliable death preventability determinations and a comprehensive list of opportunities for improvement to reduce preventable deaths within the trauma care system; and (4) acknowledgment that the military health system still has gaps in current infrastructure that must be addressed to globally and continuously implement the process outlined in the Military Trauma Mortality Review process in the future.

LEVEL OF EVIDENCE
Level III.
Evaluating and improving current risk prediction tools in emergency laparotomy
Authors: Barazanchi Ahmed , Bhat Sameer , Palmer-Neels Kate , Macfater Wiremu S. , Xia Weisi , Zeng Irene , Taneja Ashish , MacCormick Andrew D. , Hill Andrew G. 
Published: April 2020

PURPOSE
Emergency laparotomy (EL) encompasses a high-risk group of operations, which are increasingly performed on a heterogeneous population of patients, making preoperative risk assessment potentially difficult. The UK National Emergency Laparotomy Audit (NELA) recently produced a risk predictive tool for EL that has not yet been externally validated. We aimed to externally validate and potentially improve the NELA tool for mortality prediction after EL.

METHODOLOGY
We reviewed computer and paper records of EL patients from May 2012 to June 2017 at Middlemore Hospital (New Zealand). The inclusion criteria mirrored the UK NELA. We examined the NELA, Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality (P-POSSUM), Acute Physiology and Chronic Health Evaluation II (APACHE-II), and American College of Surgeons National Surgical Quality Improvement Programs risk predictive tools for 30-day mortality. The Hosmer-Lemeshow test was used to assess calibration, and the c statistic, to evaluate discrimination (accuracy) of the tools. We added the modified frailty index (mFI) and nutrition to improve the accuracy of risk predictive tools.

RESULTS
A total of 758 patients met the inclusion criteria, with an observed 30-day mortality of 7.9%. The NELA was the only well calibrated tool, with predicted 30-day mortality of 7.4% (p = 0.22). When combined with mFI and nutritional status, the c statistic for NELA improved from 0.83 to 0.88. American College of Surgeons National Surgical Quality Improvement Programs, APACHE-II, and P-POSSUM had lower c statistics, albeit also showing an improvement (0.84, 0.81, and 0.74, respectively).

CONCLUSION
We have demonstrated the NELA tool to be most predictive of mortality after EL. The NELA tool would therefore facilitate preoperative risk assessment and operative decision making most precisely in EL. Future research should consider adding mFI and nutritional status to the NELA tool.

LEVEL OF EVIDENCE
Level IV; Retrospective observational cohort study.
The Design of Lil’Flo, a Socially Assistive Robot for Upper Extremity Motor Assessment and Rehabilitation in the Community Via Telepresence
Authors: Sobrepera Michael J , Lee Vera G , Johnson Michelle J 
Published: April 2020

AbstractIntroductionWe present Lil’Flo, a socially assistive robotic telerehabilitation system for deployment in the community. As shortages in rehabilitation professionals increase, especially in rural areas, there is a growing need to deliver care in the communities where patients live, work, learn, and play. Traditional telepresence, while useful, fails to deliver the rich interactions and data needed for motor rehabilitation and assessment.MethodsFrom prior work, we have developed design requirements for a socially assistive robot for upper extremity motor assessment and rehabilitation via telepresence. We designed Lil’Flo, targeted towards pediatric patients with cerebral palsy and brachial plexus injuries. The system combines traditional telepresence and computer vision with a humanoid, who can play games with patients and guide them in a present and engaging way under the supervision of a remote clinician.ResultsThe humanoid’s arms have sufficient range of motion, and the face is able to communicate several emotions clearly. The system is portable, extensible, and cheaper than our prior iteration. A simple web interface allows operators to focus on interactions while the computer vision system stores data for analysis.ConclusionsLil’Flo represents a novel approach to delivering rehabilitation care in the community while maintaining the clinician-patient connection.
Impact of COVID-19 pandemic on severity of illness and resources required during intensive care in the greater New York City area
Authors: Badawi Omar , Liu Xinggang , Berman Iris , Amelung Pamela J , Doerfler Martin E. , Chandra Saurabh 
Published: April 2020

AbstractObjectiveDescribe the changes in patient population, bed occupancy, severity of illness and ventilator requirements across a large health system in the greater New York City area during the pandemic response in comparison with the 2019 baseline.DesignObservational, descriptive study of ICUs monitored by a tele-ICU system across Northwell Health. Inclusion criteria: All patients admitted to Northwell Health tele-ICUs during 2019 and between March 23, 2020 and April 6, 2020.ExposureA data extract was developed to collect data every hour for each ICU bed in the Northwell tele-critical care program as a quality reporting initiative to understand ICU capacity and resource utilization. A similar extract was developed for each hour of 2019.Main Outcomes and MeasuresAverage of any given hour during the pre-COVID-19 and pandemic periods for the following metrics: proportion of beds occupied, proportion of ventilated patients, severity of illness (measured by the ICU Discharge Readiness Score (DRS)), and length of stay (LOS).ResultsHourly analysis of data from 186 ICU beds from 14 ICUs and 9 hospitals were included, representing 10,714 patients in 2019 and 465 patients between March 23 and April 6, 2020. Average hourly occupancy increased from 64% to 78%, while the proportion of patients invasively ventilated increased from 33.9% to 84.2%. Median DRS (severity of illness score) increased from 1.08 (IQR: 0.24-6.98) to 39.38 (IQR: 12.00-71.28). Proportion of patients with Hispanic ethnicity doubled (7.8% to 16.6%; p<0.01) and proportion of female patients decreased from 46.3% to 32.9% (p<0.01).Conclusions and RelevanceIn addition to the expected increase in ICU occupancy and ventilator requirements, this large group of ICUs in midst of the COVID-19 epidemic are faced with managing a cohort of ICU patients with a dramatically higher severity of illness than their typical census.
Late immune-related adverse events in long-term responders to PD-1/PD-L1 checkpoint inhibitors: a multicentre study
Authors: Nigro Olga , Pinotti Graziella , De Galitiis Federica , Di Pietro Francesca Romana , Giusti Raffaele , Filetti Marco , Bersanelli Melissa , Lazzarin Alessandro , Bordi Paola , Catino Annamaria , Pizzutilo Pamela , Galetta Domenico , Marchetti Paolo , Botticelli Andrea , Scagnoli Simone , Russano Marco , Santini Daniele , Torniai Mariangela , Berardi Rossana , Ricciuti Biagio , De Giglio Andrea , Chiari Rita , Russo Alessandro , Adamo Vincenzo , Tudini Marianna , Silva Rosa Rita , Bolzacchini Elena , Giordano Monica , Di Marino Pietro , De Tursi Michele , Rijavec Erika , Ghidini Michele , Vallini Ilaria , Stucci Luigia Stefania , Tucci Marco , Pala Laura , Conforti Fabio , Queirolo Paola , Tanda Enrica , Spagnolo Francesco , Cecchi Federica , Bracarda Sergio , Macrini Serena , Santoni Matteo , Battelli Nicola , Fargnoli Maria Concetta , Porzio Giampiero , Tuzi Alessandro , Suter Matteo Basilio , Ficorella Corrado , Cortellini Alessio 
Published: April 2020

AbstractData on spectrum and grade of immune-related adverse events (irAEs) in long-term responders to immune checkpoint inhibitors (ICI) are lacking.We performed a retrospective multicenter study to characterized irAEs occurring after a 12-months minimum treatment period with PD-(L)1 ICIs in advanced cancer patients. IrAEs were categorized into “early” (≤12 months) and “late” (>12 months).From September 2013 to October 2019, 436 consecutive patients were evaluated. 223 experienced any grade early-irAEs (51.1%), while 132 experienced any grade late-irAEs (30.3%) (p < 0.0001). Among the latter, 29 (22%) experienced a recurrence of an early-irAEs, while 103 (78%) experienced de novo late-irAEs involving different system/organ. Among patients with late-irAEs, 21 experienced G3/G4 irAEs (4.8%). Median time to onset of early-irAEs was 3.4 months (95%CI: 2.8-4.2), while the median time to onset of late-irAEs was 16.6 months (95%CI: 15.8-17.6). Cumulative time-adjusted risk of disease progression according to both the early-irAEs (HR = 0.63 [95%CI: 0.30-1.29], p = 0.204) and late-irAEs occurrence revealed no statistically significant differences (HR = 0.75 [95%CI: 0.37-1.56], p = 0.452). Also the time-adjusted cumulative risk of death according to both early-irAEs (HR = 0.79 [95%CI: 0.34-1.86], p = 0.598) and late-irAEs (HR = 0.92 [95%CI: 0.49-1.74], p = 0.811) did not show statistically significant differences.Although less frequent than early-irAEs, late-irAEs are quite common in long responders to PD-(L)1 ICIs, and are different in terms of spectrum and grade. Time-adjusted analysis revealed that the cumulative risk of disease progression and death were not significantly reduced in patients who experienced late-irAEs.
Excess cases of influenza suggest an earlier start to the coronavirus epidemic in Spain than official figures tell us: an analysis of primary care electronic medical records from over 6 million people from Catalonia
Authors: Coma Ermengol , Mora Nuria , Prats-Uribe Albert , Fina Francesc , Prieto-Alhambra Daniel , Medina-Peralta Manuel 
Published: April 2020

AbstractObjectivesThere is uncertainty about when the first cases of COVID-19 appeared in Spain, as asymptomatic patients can transmit the virus. We aimed to determine whether influenza diagnoses masked early COVID-19 cases and, if so, estimate numbers of undetected COVID-19 cases in a large database of primary-care records covering >6 million people in Catalonia.DesignTime-series study of influenza and COVID-19 cases, using all influenza seasons from autumn-winter 2010-2011 to autumn-winter 2019-2020.SettingPrimary care, Catalonia, Spain.ParticipantsPeople registered in one of the contributing primary-care practices, covering >6 million people and >85% of the population.Main outcome measuresWeekly new cases of influenza and COVID-19 diagnosed in primary care.AnalysesDaily counts of both cases were computed using the total cases recorded over the previous 7 days to avoid weekly effects on recording practice. Epidemic curves were characterised for the 2010-2011 to 2019-2020 influenza seasons. Influenza seasons with a similar epidemic curve and peak case number as the 2019-2020 season were used to model predictions for 2019-2020. ARIMA models were fitted to the included influenza seasons, overall and stratified by age, to estimate expected case numbers. Daily excess influenza cases were defined as the number of observed minus expected cases.ResultsFour influenza season curves (2011-2012, 2012-2013, 2013-2014, and 2016-2017) were used to estimate the number of expected cases of influenza in 2019-2020. Between 4 February 2020 and 20 March 20202, 8,017 (95% CI: 1,841 to 14,718) excess influenza cases were identified. This excess was highest in the 15-64 age group.ConclusionsCOVID-19 cases may have been present in the Catalan population when the first imported case was reported on 25 February 2020. COVID-19 carriers may have been misclassified as influenza diagnoses in primary care, boosting community transmission before public health measures were taken. In future, the surveillance of excess influenza cases using widely available primary-care electronic medical records could help detect new outbreaks of COVID-19 or other influenza-like illness-causing pathogens. Earlier detection would allow public health responses to be initiated earlier than during the current crisis.
Scaling diagnostics in times of COVID-19: Colorimetric Loop-mediated Isothermal Amplification (LAMP) assisted by a 3D-printed incubator for cost-effective and scalable detection of SARS-CoV-2
Authors: González-González Everardo , Lara-Mayorga Itzel Montserrat , Rodríguez-Sánchez Iram Pablo , León Felipe Yee-de , García-Rubio Andrés , Garciaméndez-Mijares Carlos Ezio , Guerra-Alvarez Gilberto Emilio , García-Martínez Germán , Aguayo-Hernández Juan Andrés , Márquez-García Eduardo , Zhang Yu Shrike , Martínez-Chapa Sergio O. , Zúñiga Joaquín , Santiago Grissel Trujillo-de , Alvarez Mario Moisés 
Published: April 2020

AbstractBy the third week of June 2020, more than 8,500,000 positive cases of COVID-19 and more than 450,000 deaths had been officially reported worldwide. The COVID-19 pandemic arrived in Latin America, India, and Africa—territories in which the mounted infrastructure for diagnosis is greatly underdeveloped. Here, we demonstrate the combined use of a three-dimensional (3D)-printed incubation chamber for commercial Eppendorf PCR tubes, and a colorimetric embodiment of a loop-mediated isothermal amplification (LAMP) reaction scheme for the detection of SARS-CoV-2 nucleic acids. We used this strategy to detect and amplify SARS-CoV-2 genetic sequences using a set of in-house designed initiators that target regions encoding the N protein. We were able to detect and amplify SARS-CoV-2 nucleic acids in the range of 62 to 2 × 105 DNA copies by this straightforward method. Using synthetic SARS-CoV-2 samples and a limited number of RNA extracts from patients, we also demonstrate that colorimetric LAMP is a quantitative method comparable in diagnostic performance to RT-qPCR. We envision that LAMP may greatly enhance the capabilities for COVID-19 testing in situations where RT-qPCR is not feasible or is unavailable. Moreover, the portability, ease of use, and reproducibility of this strategy make it a reliable alternative for deployment of point-of-care SARS-CoV-2 detection efforts during the pandemics.