bluuebunny/crossref_metadata_2025 huggingface dataset:
A primer on single-cell genomics in myeloid biology
Authors: Ferchen Kyle , Song Baobao , Leighton Grimes H.
Published: November 2020

Purpose of review

Understanding the fast-moving field of single-cell technologies, as applied to myeloid biology, requires an appreciation of basic molecular, informatics, and biological concepts. Here, we highlight both key and recent articles to illustrate basic concepts for those new to molecular single-cell analyses in myeloid hematology.

Recent findings

Recent studies apply single-cell omics to discover novel cell populations, construct relationships between cell populations, reconfigure the organization of hematopoiesis, and study hematopoietic lineage tree and fate choices. Accompanying development of technologies, new informatic tools have emerged, providing exciting new insights.

Hematopoietic stem and progenitor cells are regulated by complex intrinsic and extrinsic factors to produce blood cell types. In this review, we discuss recent advances in single-cell omics to profile these cells, methods to infer cell type identify, and trajectories from molecular omics data to ultimately derive new insights into hematopoietic stem and progenitor cell biology. We further discuss future applications of these technologies to understand hematopoietic cell interactions, function, and development. The goal is to offer a comprehensive overview of current single-cell technologies and their impact on our understanding of myeloid cell development for those new to single-cell analyses.
Role of Social Networks and Social Norms in Future PrEP Use in a Racially Diverse Sample of At-Risk Women and Members of Their Social Networks
Authors: Johnson Laura M. , Green Harold D. , Koch Brandon , Stockman Jamila K. , Felsher Marisa , Roth Alexis M. , Wagner Karla D.
Published: November 2020

Objective:

Despite the efficacy of pre-exposure prophylaxis (PrEP) in reducing the risk of HIV infection, uptake remains low among many who are most vulnerable to HIV, such as Black and Latinx women. Interventions that target social networks to encourage at-risk women to initiate PrEP are underused.

Design:

This study used an egocentric network design and sampled Black/African American and Latinx women at risk of HIV as well as people from their social networks (N = 211) in a small, western city.

Methods:

Multivariable generalized linear mixed effects regression models investigated individual-level and network-level characteristics associated with likely future PrEP use.

Results:

PrEP awareness was low, but once informed, 36% considered themselves likely to take it in the future. Perceived risk of HIV, perceived barriers to HIV testing, and participation in a 12-step program increased odds of anticipated PrEP use. A higher proportion of friends in one's network decreased odds of future PrEP use, whereas a higher proportion of network members who tested regularly for HIV increased odds of future PrEP use. A marginally significant interaction was detected between proportion of friends in one's network and proportion of the network perceived to test for HIV regularly (ie, testing norms). When HIV testing norms were low, a higher proportion of friends in the network decreased odds of likely PrEP use. However, this effect was reversed in contexts with strong testing norms.

Conclusion:

Women who are interested in PrEP may be embedded within social and normative contexts that can foster or inhibit PrEP uptake.
Facial Contour Rejuvenation by Reduction Malarplasty Combined With Second-Stage Fat Grafting
Authors: Gao Bowen , Yuan Yukun , Li Ke , Li Zengguang , Yu Lianggang
Published: November 2020

Background:

With aging, the facial contour shows a double-concave deformity. Conventional facial contouring procedure, including face lifting and fat grafting, cannot yield a smooth facial contour line. This study was the first to propose a combination of reduction malarplasty and 2nd-stage autologous fat grafting so as to achieve the aesthetic goals of facial contour rejuvenation.

Methods:

The study group comprised patients seeking facial contour rejuvenation from January 2017 to May 2018 (28 patients: 28 females and 0 males) at the Department of Plastic Surgery, Tian Tan Pu Hua Hospital. All of the cases underwent bilateral malarplasty with 2nd-stage autologous facial fat grafting. Radiologic and photographic documentation was completed preoperatively. The mean follow-up period was 12 months. Patients’ pre-op photographs and 3 months follow-up pictures were blindly assessed.

Results:

Most of the patients were satisfied with their results after 1-time fat grafting. Eleven patients demanded re-injection after the 1st fat grafting in temporal area, and 6 patients demanded 3rd time fat grafting in temporal area. Eleven patients demanded re-injection insubmalar area, and 8 patients demanded 3rd time fat grafting in submalar area. Meanwhile, 9 of those patients underwent fat grafting in other sites other than temporal and submalar region. The amount of fat injected was also recorded in this study. The appearance of double-concave deformity was greatly improved in all cases. Complications included infection (3.6%), hematoma (7.1%), and malar prominence relapse (7.1%), and so on.

Conclusion:

Reduction malarplasty combined with several times of fat grafting could effectively overcome the malar prominence and soft tissue deflation. Complications were minimal after these procedures. Therefore, this technique is useful to restore the youthful facial contour in Asian patients with aging double-concave deformity.
Reconstruction of Posttraumatic Nasal Defect Through Paramedian Frontal Flap
Authors: Gonçalves Kalyne Kelly Negromonte , Lessa Thayane Celina Silva , Diniz Demóstenes Alves , Silva Ana Fábia dos Santos , Luz Luciano Leal , Filho Dirceu de Oliveira , Vasconcelos Belmiro Cavalcanti do Egito
Published: November 2020

Facial injuries caused by motorcycle accidents represent a challenge for reconstructions. Currently, the most indicated treatment for facial fractures is anatomical reduction and internal fixation, however, this procedure is not exempt from complications, such as infection and exposure of osteosynthesis material, thus requiring a new surgical procedure and repair. In this study, the authors describe a case of a 60-year-old woman who was the victim of a motorcycle accident and developed exposure of osteosynthesis material on the nasal dorsum after treatment of facial fractures. The patient underwent surgical treatment with objective of removing the osteosynthesis material and associated infected tissue, as well as reconstruction using a paramedian frontal flap, which resulted in a harmonic relationship and skin color similar to the recipient area. This case shows the importance of anatomical knowledge and reconstructive techniques for hard and soft tissues.
Network Analysis of Postoperative Surgical Complications in a Cohort of Children Reported to the National Surgical Quality Improvement Program
Authors: Alzubaidi Ahmad N. , Karabayir Ibrahim , Akbilgic Oguz , Langham Max R.
Published: November 2020

Objective:

To understand the temporal relationships of postoperative complications in children and determine if they are related to each other in a predictable manner.

Summary of Background Data:

Children with multiple postoperative complications have increased suffering and higher risk for mortality. Rigorous analysis of the temporal relations between complications, how complications might cluster, and the implications of such clusters for children have not been published. Herein, we analyze the relationships between postoperative complications in children.

Methods:

Data source: Surgical operations included in the National Surgical Quality Improvement Program Pediatric Participant Use Data File from 2013 to 2017. The main outcomes measure was presence of 1 or more postoperative complications within 30 days of surgery. Operations followed by multiple complications were analyzed using network analysis to study prevalence, timing, and co-occurrences of clusters of complications.

Results:

This study cohort consisted of 432,090 operations; 388,738 (89.97%) had no postoperative complications identified, 36,105 (8.35%) operations resulted in 1 postoperative complication and 7247 (1.68%) operations resulted in 2 or more complications. Patients with multiple complications were more likely to be younger, male, African American, with a higher American Society of Anesthesiologists score, and to undergo nonelective operations (P < 0.001). More patients died with 2 complication versus 1 complication vs no complication (5.3% vs 1.5% vs 0.14%, P < 0.001). Network analysis identified 4 Louvain clusters of complications with dense intracluster relationships.

Conclusions:

Children with multiple postoperative complications are at higher risk of death, than patients with no complication, or a single complication. Multiple complications are grouped into defined clusters and are not independent.
Prophylactic Single-use Negative Pressure Dressing in Closed Surgical Wounds After Incisional Hernia Repair
Authors: Bueno-Lledó José , Franco-Bernal Ascensión , Garcia-Voz-Mediano María Teresa , Torregrosa-Gallud Antonio , Bonafé Santiago
Published: November 2020

Objective:

A randomized controlled trial (RCT) was undertaken to evaluate whether the prophylactic application of a specific single-use negative pressure (sNPWT) dressing on closed surgical incisions after incisional hernia (IH) repair decreases the risk of surgical site occurrences (SSOs) and the length of stay.

Background:

The sNPWT dressings have been associated to several advantages like cost savings and prevention of SSOs like seroma, hematoma, dehiscence, or wound infection (SSI) in closed surgical incisions. But this beneficious effect has not been previously studied in cases of close wounds after abdominal wall hernia repairs.

Methods:

An RCT was undertaken between May 2017 and January 2020 (ClinicalTrials.gov registration number NCT03576222). Participating patients, with IH type W2 or W3 according to European Hernia Society classification, were randomly assigned to receive intraoperatively either the sNPWT (PICO)(72 patients) or a conventional dressing at the end of the hernia repair (74 patients). The primary endpoint was the development of SSOs during the first 30 days after hernia repair. The secondary endpoint included length of hospital stay. Statistical analysis was performed using IBM SPSS Statistics Version 23.0.

Results:

At 30 days postoperatively, there was significatively higher incidence of SSOs in the control group compared to the treatment group (29.8% vs 16.6%, P < 0.042). There was no SSI in the treatment group and 6 cases in the control group (0% vs 8%, P < 0.002). No significant differences regarding seroma, hematoma, wound dehiscence, and length of stay were observed between the groups.

Conclusion:

The use of prophylactic sNPWT PICO dressing for closed surgical incisions following IH repair reduces significatively the overall incidence of SSOs and the SSI at 30 days postoperatively.
Open Versus Laparoscopic Repair of Perforated Peptic Ulcer Disease
Authors: Coe Peter O. , Lee Matthew J. , Boyd-Carson Hannah , Lockwood Sonia , Saha Arin
Published: November 2020

Objective:

The aim of this study was to compare open surgery (OS) with laparoscopic surgery (LS) for perforated peptic ulcer (PPU) disease using a National dataset.

Background:

PPU disease is typically treated surgically with an omental patch. This can be performed through OS or a LS. Current evidence in OS versus LS suggests equivalence in mortality and postoperative complications, but a decrease in pain and wound infections with LS.

Methods:

A one-to-one propensity score-matched analysis of patients who underwent PPU repair from December 2013 to December 2017 using data from the National Emergency Laparotomy Audit was performed. Patients with an initially laparoscopic approach were classed as LS even if converted to OS. The primary end-point was 90-day mortality; secondary endpoints were length of stay (LOS), re-operation, and re-admission to critical care. Multivariable logistic and linear models were created to compare the effect of operative approach on binary and continuous outcomes with log-rank tests for time-to-event data.

Results:

A total of 5253 patients underwent surgery in the study period. After propensity-matching, 2 groups of 1158 patients were created. Overall 90-day mortality was 7.5%. There was no difference between the LA and OA for 90-day mortality (7.2% vs 8.5%, OR 0.80, 95% CI 0.56– 1.15, P = 0.23), median LOS (equivalent at 7 days, P = 0.09), reoperation (3.6% vs 4.0%, P = 0.74), or re-admission to critical care (2.8% vs 2.9%, P = 0.92). Across the 4-year study period LS use increased from 20% to 26% and the conversion rate decreased from 40% to 31%.

Conclusions:

Short outcomes from laparoscopic PPU repair appear equivalent to open repair. There is increasing adoption of LS with decreasing conversion rates. LS for PPU appears to be an acceptable approach in this setting.
Evaluating the Impact of Surgeon Self-awareness by Comparing Self Versus Peer Ratings of Surgical Skill and Outcomes for Bariatric Surgery
Authors: Varban Oliver A. , Thumma Jyothi R. , Carlin Arthur M. , Ghaferi Amir A. , Dimick Justin B. , Finks Jonathan F.
Published: November 2020

Objective:

To evaluate variation in self versus peer-assessments of surgical skill using surgical videos and compare surgeon-specific outcomes with bariatric surgery.

Summary Background Data:

Prior studies have demonstrated that surgeons with lower peer-reviewed ratings of surgical skill had higher complication rates after bariatric surgery.

Methods:

This is a retrospective cohort study of 25 surgeons who voluntarily submitted a video of a typical laparoscopic sleeve gastrectomy (SG) between 2015 and 2016. Videos were self and peer-rated using a validated instrument based on a 5-point Likert scale (5= “master surgeon” and 1= “surgeon-in-training”). Risk adjusted 30-day complication rates were compared between surgeons who over-rated and under-rated their skill based on data from 24,186 SG cases and 12,888 gastric bypass (GBP) cases.

Results:

individual overall self-rating of surgical skill varied between 2.5 and 5. Surgeons in the top quartile for self:peer ratings (n = 6, ratio 1.58) had lower overall mean peer-scores (2.98 vs 3.79, P = 0.0150) than surgeons in the lowest quartile (n = 6, ratio 0.94). Complication rates between top and bottom quartiles were similar after SG, however leak rates were higher with gastric bypass among surgeons who over-rated their skill with SG (0.65 vs 0.27, P = 0.0181). Surgeon experience was similar between comparison groups.

Conclusions and Relevance:

Self-perceptions of surgical skill varied widely. Surgeons who over-rated their skill had higher leak rates for more complex procedures. Video assessments can help identify surgeons with poor self-awareness who may benefit from a surgical coaching program.
Pancreatobiliary Maljunction-associated Gallbladder Cancer Is as Common in the West, Shows Distinct Clinicopathologic Characteristics and Offers an Invaluable Model for Anatomy-induced Reflux-associated Physio-chemical Carcinogenesis
Authors: Muraki Takashi , Pehlivanoglu Burcin , Memis Bahar , Reid Michelle D. , Uehara Takeshi , Basturk Olca , Pernicka Jennifer Golia , Klimstra David S. , Jarnagin William R. , Ito Tetsuya , Hasebe Osamu , Okaniwa Shinji , Horigome Naoto , Hisa Takeshi , Mittal Pardeep , Sarmiento Juan M. , Maithel Shishir K. , Koshiol Jill , Tsai Susan , Evans Douglas , Erkan Mert , Adsay Volkan
Published: November 2020

Objective:

To determine the associations of pancreatobiliary maljunction (PBM) in the West.

Background:

PBM (anomalous union of common bile duct and pancreatic duct) is mostly regarded as an Asian-only disorder, with 200X risk of gallbladder cancer (GBc), attributed to reflux of pancreatic enzymes. Methods: Radiologic images of 840 patients in the US who underwent pancreatobiliary resections were reviewed for PBM and contrasted with 171 GBC cases from Japan.

Results:

Eight % of the US GBCs (24/300) had PBM (similar to Japan; 15/ 171, 8.8%), in addition to 1/42 bile duct carcinomas and 5/33 choledochal cysts. None of the 30 PBM cases from the US had been diagnosed as PBM in the original work-up. PBM was not found in other pancreatobiliary disorders. Clinicopathologic features of the 39 PBM-associated GBCs (US:24, Japan:15) were similar; however, comparison with non-PBM GBCs revealed that they occurred predominantly in females (F/M = 3); at younger (<50-year-old) age (21% vs 6.5% in non-PBM GBCs; P = 0.01); were uncommonly associated with gallstones (14% vs 58%; P < 0.001); had higher rate of tumor-infiltrating lymphocytes (69% vs 44%; P = 0.04); arose more often through adenoma-carcinoma sequence (31% vs 12%; P = 0.02); and had a higher proportion of nonconventional carcinomas (21% vs 7%; P = 0.03). Conclusions: PBM accounts for 8% of GBCs also in the West but is typically undiagnosed. PBM-GBCs tend to manifest in younger age and often through adenoma-carcinoma sequence, leading to unusual carcinoma types. If PBM is encountered, cholecystectomy and surveillance of bile ducts is warranted. PBM-associated GBCs offer an invaluable model for variant anatomy-induced chemical (reflux-related) carcinogenesis.
Invasive and Noninvasive Progression After Resection of Noninvasive Intraductal Papillary Mucinous Neoplasms
Authors: Amini Neda , Habib Joseph R. , Blair Alex , Rezaee Neda , Kinny-Köster Benedict , Cameron John L. , Hruban Ralph H. , Weiss Matthew J. , Fishman Elliot K. , Lafaro Kelly J. , Zaheer Atif , Manos Lindsey , Burns William R. , Burkhart Richard , He Jin , Yu Jun , Wolfgang Christopher L.
Published: November 2020

Objective:

To define frequencies, pattern of progression (invasive vs noninvasive), and risk factors of progression of resected noninvasive intraductal papillary mucinous neoplasms (IPMNs).

Background:

There is a risk of progression in the remnant pancreas after resection of IPMNs.

Methods:

Four hundred forty-nine consecutive patients with resected IPMNs from 1995 to 2018 were included to the study. Patients with invasive carcinoma or with follow-up <6 months were excluded. Noninvasive progression was defined as a new IPMN, increased main pancreatic duct size, and increased size of an existing lesion (5 mm compared with preoperative imaging). Invasive progression was defined as development of invasive cancer in the remnant pancreas or metastatic disease.

Results:

With a median follow-up of 48.9 months, progression was identified in 124 patients (27.6%); 108(24.1%) with noninvasive and 16(3.6%) with invasive progression. Median progression follow-up was longer for invasive progression (85.4 vs 55.9 months; P = 0.001). Five-and 10-year estimates for a cumulative incidence of invasive progression were 6.4% and 12.9% versus 26.9% and 41.5% for noninvasive progression. After risk adjustment, multifocality (HR 4.53, 95% CI 1.34–15.26; P = 0.02) and high-grade dysplasia (HGD) in the original resection (HR 3.60, 95% CI 1.13–11.48; P = 0.03) were associated with invasive progression.

Conclusions:

Progression to invasive carcinoma can occur years after the surgical resection of a noninvasive IPMN. HGD in the original resection is a risk factor for invasive progression but some cases of low-grade dysplasia also progressed to cancer. Patients with high-risk features such as HGD and multifocal cysts should be considered for more intensive surveillance and represent an important cohort for future trials such as anti-inflammatory or prophylactic immunotherapy.
The Impact of Prehabilitation on Patient Outcomes in Hepatobiliary, Colorectal, and Upper Gastrointestinal Cancer Surgery
Authors: Lambert Joel E. , Hayes Lawrence D. , Keegan Thomas J. , Subar Daren A. , Gaffney Christopher J.
Published: November 2020

Objective:

To determine the impact of prehabilitation on hospital length of stay, functional capacity, complications, and mortality after surgery in patients with hepatobiliary, colorectal, and upper gastrointestinal cancer.

Background:

“Prehabilitation” encompasses exercise, nutrition, and psychosocial interventions to optimize health before surgery. The benefits of prehabilitation are ill-defined.

Methods:

Medline, Embase and Cochrane Databases were searched systematically for the terms “prehabilitation AND exercise,” “perioperative care AND cancer surgery,” and “colorectal AND hepatobiliary AND hepatopancreatobiliary AND esophagogastric AND recovery AND outcomes.” Primary outcomes analyzed were hospital length of stay, functional capacity, significant postoperative complications (Clavien Dindo ≥ III), and mortality. A meta-analysis was conducted on the effect of all-modality prehabilitation for patients with colorectal, hepatopancreatobiliary and upper gastrointestinal cancer surgery using the raw mean difference, risk difference, and a random-effects model.

Results:

Three hundred and seventy seven original titles were identified. Fifteen studies (randomized controlled trials; n = 9 and uncontrolled trials; n = 6) were included in the meta-analysis. Prehabilitation reduced hospital length of stay by 1.78 days versus standard care (95% CI: −3.36, −0.20, P < 0.05). There was no significant difference in functional capacity with prehabilitation determined using the 6-minute walk test (P = 0.816) and no significant reduction in postoperative complications (P = 0.378) or mortality rates (P = 0.114).

Conclusions:

Prehabilitation was associated with reduced hospital length of stay but had no effect on functional capacity, postoperative complications, or mortality rates. Thus, prehabilitation should be recommended to accelerate recovery from cancer surgery, demonstrated by reduced hospital length of stay.
Immediate Oral Refeeding in Patients With Mild and Moderate Acute Pancreatitis
Authors: Ramírez-Maldonado Elena , López Gordo Sandra , Pueyo Eva M. , Sánchez-García Ariadna , Mayol Susana , González Sergio , Elvira Jordi , Memba Robert , Fondevila Constantino , Jorba Rosa
Published: November 2020

Objective:

To establish the optimal time to start oral refeeding in mild and moderate acute pancreatitis (AP) to reduce hospital length-of-stay (LOS) and complications.

Summary Background Data:

Oral diet is essential in mild and moderate AP. The greatest benefits are obtained if refeeding starts early; however, the definition of “early” remains controversial.

Methods:

This multicenter, randomized, controlled trial (NCT03829085) included patients with a diagnosis of mild or moderate AP admitted consecutively to 4 hospitals from 2017 to 2019. Patients were randomized into 2 treatment groups: immediate oral refeeding (IORF) and conventional oral refeeding (CORF). The IORF group (low-fat-solid diet initiated immediately after hospital admission) was compared to CORF group (progressive oral diet was restarted when clinical and laboratory parameters had improved) in terms of LOS (primary endpoint), pain relapse, diet intolerance, complications, and, hospital costs.

Results:

One hundred and thirty one patients were included for randomization. The mean LOS for the IORF and CORF groups was 3.4 (SD ± 1.7) and 8.8 (SD ± 7.9) days, respectively (P < 0.001). In the CORF group alone, pain relapse rate was 16%. There were fewer complications (8% vs 26%) and health costs were twice as low, with a savings of 1325.7€/patient in the IORF than CORF group.

Conclusions:

IORF is safe and feasible in mild and moderate AP, resulting in significantly shorter LOS and cost savings, without causing adverse effects or complications.
Acute Kidney Injury in Deceased Organ Donors and Kidney Transplant Outcomes
Authors: Sonnenberg Elizabeth M. , Hsu Jesse Y. , Cohen Jordana B. , Potluri Vishnu S. , Geng Zhi , Levine Matthew H. , Abt Peter L. , Reese Peter P.
Published: November 2020

Objective:

The aim of this study was to determine graft function and survival for kidney transplants from deceased donors with acute kidney injury (AKI) that persists at the time of organ procurement.

Background:

Kidneys from donors with AKI are often discarded and may provide an opportunity to selectively expand the donor pool.

Methods:

Using Organ Procurement and Transplantation Network and DonorNet data, we studied adult kidney-only recipients between May 1, 2007 and December 31, 2016. DonorNet was used to characterize longitudinal creatinine trends and urine output. Donor AKI was defined using KDIGO guidelines and terminal creatinine ≥1.5 mg/dL. We compared outcomes between AKI kidneys versus “ideal comparator” kidneys from donors with no or resolved AKI stage 1 plus terminal creatinine <1.5mg/dL. We fit proportional hazards models and hierarchical linear regression models for the primary outcomes of all-cause graft failure (ACGF) and 12-month estimated glomerular filtration rate (eGFR), respectively.

Results:

We identified 7660 donors with persistent AKI (33.2% with AKI stage 3) from whom ≥1 kidney was transplanted. Observed rates of ACGF within 3 years were similar between recipient groups (15.5% in AKI vs 15.1% ideal comparator allografts, P = 0.2). After risk adjustment, ACGF was slightly higher among recipients of AKI kidneys (adjusted hazard ratio 1.05, 95% confidence interval: 1.01–1.09). The mean 12-month eGFR for AKI kidney recipients was lower, but differences were not clinically important (56.6 vs 57.5 mL/min/1.73m2 for ideal comparator kidneys; P < 0.001). There were 2888 kidneys discarded from donors with AKI, age ≤65 years, without hypertension or diabetes, and terminal creatinine ≤4 mg/dL.

Conclusion:

Kidney allografts from donors with persistent AKI are often discarded, yet those that were transplanted did not have clinically meaningful differences in graft survival and function.
Sex-Based Role Misidentification and Burnout of Resident Physicians
Authors: Jain Nina , Rome Benjamin N. , Foote Michael B. , DeFilippis Ersilia M. , Powe Camille E. , Yialamas Maria A.
Published: November 2020

Objective:

This cross-sectional study characterized associations between sex, role misidentification, and burnout among surgical and nonsurgical residents.

Summary Background Data:

Limited evidence suggests that female resident physicians are more likely to be misidentified as nonphysician team members, with potential negative implications for wellbeing. The prevalence and impact of role misidentification on the trainee experience in surgical as compared to nonsurgical specialties is unknown.

Methods:

An anonymous electronic survey was distributed to fourteen different residency programs at 2 academic medical centers in August 2018. The survey included questions about demographics, symptoms of burnout, the frequency of misidentification as another member of the care team, and the effect of misidentification on respondents’ well-being. Results: Two-hundred sixty out of 419 (62.1% response rate) resident physicians completed the survey, of whom 184 (77.3%) reported being misidentified as a nonphysician at least weekly. Female sex was associated with a significantly increased odds of being misidentified at least weekly (adjusted OR 23.7, 95% CI 10.9–51.5; P < 0.001), as was training in a surgical program (adjusted OR 3.7, 95% CI 1.7–8.0; P = 0.001). Frequent role misidentification was associated with burnout (OR 2.6, 95% CI 1.2–5.5; P = 0.01). In free-text responses, residents reported that being misidentified invoked a sense of not belonging, caused emotional exhaustion, and interfered with patient communication.

Conclusions:

Role misidentification is more prevalent among female residents and surgical residents, compared to male residents and nonsurgical residents, respectively. Physician role misidentification is associated with burnout and has negative implications for resident wellbeing; interventions to reduce role misidentification are needed.
Electrocardiographic Abnormalities and Troponin Elevation in COVID-19
Authors: Chorin Ehud , Dai Matthew , Kogan Edward , Wadhwani Lalit , Shulman Eric , Nadeau-Routhier Charles , Knotts Robert , Bar-Cohen Roi , Barbhaiya Chirag , Aizer Anthony , Holmes Douglas , Bernstein Scott , Spinelli Michael , Park David , Chinitz Larry , Jankelson Lior
Published: November 2020

Background

the COVID19 pandemic has resulted in worldwide morbidity at unprecedented scale. Troponin elevation is a frequent laboratory finding in hospitalized patients with the disease, and may reflect direct vascular injury or nonspecific supply-demand imbalance. In this work, we assessed the correlation between different ranges of Troponin elevation, Electrocardiographic (ECG) abnormalities and mortality.

Methods

We retrospectively studied 204 consecutive patients hospitalized at NYU Langone Health with COVID19. Serial ECG tracings were evaluated in conjunction with laboratory data including Troponin. Mortality was analyzed in respect to the degree of Troponin elevation and the presence of ECG changes including ST elevation, ST depression or T wave inversion.

Results

Mortality increased in parallel with increase in Troponin elevation groups and reached 60% when Troponin was >1 ng/ml. In patients with mild Troponin rise (0.05 – 1.00 ng/ml) the presence of ECG abnormality resulted in significantly greater mortality.

Conclusion

ECG repolarization abnormalities may represent a marker of clinical severity in patients with mild elevation in Troponin values. This finding can be used to enhance risk stratification in patients hospitalized with COVID19.
Survival prediction for bladder cancer using machine learning: development of BlaCaSurv online survival prediction application
Authors: Das Ashis Kumar , Mishra Shiba , Mishra Devi Kalyan , Gopalan Saji Saraswathy
Published: November 2020

Background

Bladder cancer is the most common cancer of the urinary system among the American population and it is the fourth most common cause of cancer morbidity and the eight most common cause of cancer mortality among men. Using machine learning algorithms, we predict the five-year survival among bladder cancer patients and deploy the best performing algorithm as a web application for survival prediction.

Methods

Microscopically confirmed adult bladder cancer patients were included from the Surveillance Epidemiology and End Results (SEER) database (2000-2017) and randomly split into training and test datasets (70/30 ratio). Five machine learning algorithms (logistic regression, support vector machine, gradient boosting, random forest, and K nearest neighbor) were trained on features to predict five-year survival. The algorithms were compared with performance metrics and the best performing algorithm was deployed as a web application.

Results

A total of 52,529 patients were included in our study. The gradient boosting algorithm was the best performer in terms of predictive ability and discrimination. It was deployed as the survival prediction web application named BlaCaSurv (https://blacasurv.herokuapp.com/).

Conclusions

We tested several machine learning algorithms and developed a web application for predicting five-year survival for bladder cancer patients. This application can be used as a supplementary prognostic tool to clinical decision making.
Antiretroviral treatment-induced decrease in immune activation contributes to reduced susceptibility to tuberculosis in HIV-1-TB co-infected persons
Authors: Wilkinson Katalin A. , Schneider-Luftman Deborah , Lai Rachel , Barrington Christopher , Jhilmeet Nishtha , Lowe David M , Kelly Gavin , Wilkinson Robert J
Published: November 2020

Antiretroviral treatment (ART) reduces the risk of developing active tuberculosis (TB) in HIV-1 co-infected persons. In order to understand host immune responses during ART in the context of Mycobacterium tuberculosis (Mtb) sensitization, we performed RNAseq analysis of whole blood-derived RNA from HIV-1 infected patients during the first 6 months of ART. A significant fall in RNA sequence abundance of the Hallmark IFN-alpha, IFN-gamma, IL- 6/JAK/STAT3 signaling, and inflammatory response pathway genes indicated reduced immune activation and inflammation at 6 months of ART compared to day 0. Further exploratory evaluation of 65 soluble analytes in plasma confirmed the significant decrease of inflammatory markers after 6 months of ART. Next, we evaluated 30 soluble analytes in QuantiFERON Gold in-tube (QFT) samples from the Ag stimulated and Nil tubes, during the first 6 months of ART in 30 patients. There was a significant decrease in IL-1alpha and IL-1beta (Ag-Nil) concentrations as well as MCP-1 (Nil), supporting decreased immune activation and inflammation. At the same time, IP-10 (Ag-nil) concentrations significantly increased, together with chemokine receptor-expressing CD4 T cell numbers. Our data indicate that ART-induced decrease in immune activation combined with improved antigen responsiveness may contribute to reduced susceptibility to tuberculosis in HIV-1-TB co-infected persons.
Wastewater-based Epidemiology for Averting COVID-19 Outbreaks on The University of Arizona Campus
Authors: Betancourt Walter W. , Schmitz Bradley W. , Innes Gabriel K. , Pogreba Brown Kristen M. , Prasek Sarah M. , Stark Erika R. , Foster Aidan R. , Sprissler Ryan S. , Harris David T. , Sherchan Samendra P. , Gerba Charles P. , Pepper Ian L.
Published: November 2020

The University of Arizona utilized wastewater-based epidemiology paired with clinical testing as a surveillance strategy to monitor COVID-19 prevalence in a dormitory community. Positive SARS-CoV-2 RNA detection in wastewater led to prompt testing of all residents and the identification and isolation of three infected individuals which averted potential disease transmission.

Text

Wastewater-based epidemiology (WBE) utilizes concentrations of SARS-CoV-2 in sewage to monitor population-level COVID-19 infections(1–3). Currently, WBE is a promising indicator to support public health decisions(3,4). In this case study, WBE was used to detect a COVID-19 outbreak in a student dormitory (henceforth Dorm A) at the University of Arizona (UArizona).

The Study

UArizona incorporated wastewater surveillance as a potential early-warning tool for COVID-19 outbreaks on campus. Grab samples (1L) were collected from a sewer manhole specific to Dorm A, between August 18-31 to monitor SARS-CoV-2 RNA in wastewater. Upon positive detection of viral RNA in wastewater samples, clinical testing was conducted on every individual living in the dorm. UArizona performed two clinical testing modalities, antigen (1 hour turnaround) test via anterior nasal swab and RT-PCR (48-72 hour turnaround) via nasopharyngeal swab samples. Individuals were subject to clinical testing via two routes: Campus Health Services (CHS) if experiencing symptoms or Test All Test Smart (TATS) regardless of symptoms. Refer to Appendix for method details.

Article Summary Line

Wastewater-based epidemiology with subsequent clinical testing identified individuals infected with COVID-19 living in a dormitory and further spread of disease was prevented with public health action.
What is the relationship between validated frailty scores and mortality for adults with COVID-19 in acute hospital care? A systematic review
Authors: Cosco Theodore D. , Best John , Davis Daniel , Bryden Daniele , Arkill Suzanne , Oppen James van , Riadi Indira , Conroy Simon
Published: November 2020

Background & aim

The aim of this systematic review was to quantify the association between frailty and COVID-19 in relation to mortality in hospitalised patients.

Methods

Medline, Embase, Web of Science and the grey literature were searched for papers from inception to 10th September 2020; the search was re-run in Medline up until the 9th December 2020. Screening, data extraction and quality grading were undertaken by two reviewers. Results were summarised using descriptive statistics, including a meta-analysis of overall mortality; the relationships between frailty and COVID-19 mortality were summarised narratively.

Results

2286 papers were screened resulting in 26 being included in the review. Most studies were from Europe, half from the UK, and one from Brazil; the median sample size was 242.5, median age 73.1 and 43.5% were female. 22/26 used the Clinical Frailty Scale; reported mortality ranged from 14 to 65%. Most, but not all studies showed an association between increasing frailty and a greater risk of dying. Two studies indicated a sub-additive relationship between frailty, COVID-19 and death, and two studies showed no association.

Conclusions

Whilst the majority of studies have shown a positive association between COVID-19 related death and increasing frailty, some studies suggested a more nuanced understanding of frailty and outcomes in COVID-19 is needed. Clinicians should exert caution in placing too much emphasis on the influence of frailty alone when discussing likely prognosis in older people with COVID-19 illness.

Key points

Frailty is being used to assess the risk of dying from COVID-19

Emerging studies demonstrate a complex relationship between frailty and COVID-19 related deaths

Clinicians should exert caution in placing too much emphasis on the influence of frailty in older people with COVID-19

Researchers should ensure that frailty scales are used as designed when planning and reporting future research.
No evidence of increase in suicide in Greece during the first wave of Covid-19
Authors: Vandoros Sotiris , Theodorikakou Olga , Katsadoros Kyriakos , Zafeiropoulou Dimitra , Kawachi Ichiro
Published: November 2020

Background and Objective

Mental health outcomes have reportedly worsened in several countries during the Covid-19 pandemic and associated lockdowns. In the present study we examined whether suicides increased in Greece during the first wave of the pandemic.

Methods

We used daily suicide estimates from a Suicide Observatory in Greece from 2015-2020 and followed three methodologies: A descriptive approach, an interrupted time series analysis, and a differences-in-differences econometric model.

Results

We did not find any empirical evidence of any increase in suicides during the first wave of Covid-19 and the lockdown in any of the three approaches used.

Conclusions

Suicides did not seem to increase during the first wave of covid-19 and lockdown in Greece. However, this does not mean that mental health did not deteriorate, or that we will not observe an increase in suicides during the second wave. Protective factors for Greece during the first wave may include working from home (for those able to tele-work), strong family ties, advertising of a suicide hotline and income support for the unemployed.
Ethical and practical considerations in HIV drug trial closure: perspectives of research staff in Uganda
Authors: Nalubega Sylivia , Cox Karen , Mugerwa Henry , Evans Catrin
Published: November 2020

There is a gap in evidence regarding how research trial closure processes are managed to ensure continuity of HIV care for HIV positive participants following trial closure within low income settings. This research aimed to establish how research staff in Uganda understood and practised post-trial care for HIV positive trial participants. A grounded theory study was conducted using in-depth individual interviews and focus group discussions with 22 research staff from 3 different trials in Uganda, in 2014-2015. The results indicated that researchers engaged in three main activities to support trial participants, including; (i) preparing for post-trial care, which included instituting trial closure guidelines, planning necessary resources, and informing trial participants about post-trial care; (ii) facilitating participants during trial exit by engaging in psychological and practical support activities, and (iii) providing follow up care and support for participants after trial exit, to respond to the needs of trial participants which often arose after trial exit. This study established a need for a holistic approach to post-trial-care of HIV positive trial participants in Uganda, and the need to engage multiple stakeholders including ethics authorities.
Molecular docking-based screening for novel inhibitors of the human immunodeficiency virus type 1 protease that effectively reduce the viral replication in human cells
Authors: Mavian Carla , Coman Roxana M , Zhang Xinrui , Pomeroy Steve , Ostrov David A. , Dunn Ben M , Sleasman John W. , Goodenow Maureen M
Published: November 2020

Therapeutic pressure by protease inhibitors (PIs) contributes to accumulation of mutations in the HIV type 1 (HIV-1) protease (PR) leading to development of drug resistance with subsequent therapy failure. Current PIs target the active site of PR in a competitive manner. Identification of molecules that exploit non-active site mechanisms of inhibition is essential to overcome resistance to current PIs. Potential non-active site HIV-1 protease (PR) inhibitors (PI) were identified by in silico screening of almost 140,000 molecules targeting the hinge region of PR. Inhibitory activity of best docking compounds was tested in an in vitro PR inhibition biochemical assay. Five compounds inhibited PR from multiple HIV-1 subtypes in vitro and reduced replicative capacity by PI-sensitive or multi-PI resistant HIV-1 variants in human cells ex vivo. Antiviral activity was boosted when combined with Ritonavir, potentially diminishing development of drug resistance, while providing effective treatment for drug resistant HIV-1 variants.
Aversive Conditioning of Spatial Position Sharpens Neural Population-level Tuning in Visual Cortex and Selectively Reduces Alpha-band Activity
Authors: Friedl Wendel M. , Keil Andreas
Published: November 2020

Processing capabilities for many low-level visual features are experientially malleable, aiding sighted organisms in adapting to dynamic environments. Explicit instructions to attend a specific visual field location influence retinotopic visuocortical activity, amplifying responses to stimuli appearing at cued spatial positions. It remains undetermined, however, both how such prioritization affects surrounding non-prioritized locations, and if a given retinotopic spatial position can attain enhanced cortical representation through experience rather than instruction. This work examined visuocortical response changes as human observers learned, through differential classical conditioning, to associate specific on-screen locations with aversive outcomes. Using dense-array EEG and pupillometry, we tested the pre-registered hypotheses of either sharpening or generalization around an aversively associated location following a single conditioning session. Specifically, competing hypotheses tested if mean response changes would take the form of a gaussian (generalization) or difference-of-gaussian (sharpening) distribution over spatial positions, peaking at the viewing location paired with a noxious noise. Occipital 15 Hz steady-state visual evoked potential (ssVEP) responses were selectively heightened when viewing aversively paired locations and displayed a non-linear, difference-of-gaussian profile across neighboring locations, consistent with suppressive surround modulation of non-prioritized positions. Measures of alpha band (8 – 12.8 Hz) activity and pupil diameter also exhibited selectively heightened responses to noise-paired locations but did not evince any difference across the non-paired locations. These results indicate that visuocortical spatial representations are sharpened in response to location-specific aversive conditioning, while top-down influences indexed by alpha power reduction exhibit all-or-none modulation.

Significance Statement

It is increasingly recognized that early visual cortex is not a static processor of physical features, but is instead constantly shaped by perceptual experience. It remains unclear, however, to what extent the cortical representation of many fundamental features, including visual field location, is malleable by experience. Using EEG and an aversive classical conditioning paradigm, we observed sharpening of visuocortical responses to stimuli appearing at aversively associated locations along with location-selective facilitation of response systems indexed by pupil diameter and EEG alpha power. These findings highlight the experience-dependent flexibility of retinotopic spatial representations in visual cortex, opening avenues towards novel treatment targets in disorders of attention and spatial cognition.
Effects of inactivation method on SARS-CoV-2 virion protein and structure
Authors: Loveday Emma K. , Hain Kyle S. , Kochetkova Irina , Hedges Jodi F. , Robison Amanda , Snyder Deann T. , Brumfield Susan K. , Young Mark J. , Jutila Mark A. , Chang Connie B. , Taylor Matthew P.
Published: November 2020

The risk posed by Severe Acute Respiratory Syndrome Coronavirus −2 (SARS-CoV-2) dictates that live-virus research is conducted in a biosafety level 3 (BSL3) facility. Working with SARS-CoV-2 at lower biosafety levels can expedite research yet requires the virus to be fully inactivated. In this study, we validated and compared two protocols for inactivating SARS-CoV-2: heat treatment and ultraviolet irradiation. The two methods were optimized to render the virus completely incapable of infection while limiting destructive effects of inactivation. We observed that 15 minutes of incubation at 65°C completely inactivates high titer viral stocks. Complete inactivation was also achieved with minimal amounts of UV power (70,000 μJ/cm2), which is 100-fold less power than comparable studies. Once validated, the two methods were then compared for viral RNA quantification, virion purification, and antibody recognition. We observed that UV irradiation resulted in a 2-log reduction of detectable genomes compared to heat inactivation. Protein yield following virion enrichment was equivalent for all inactivation conditions, but the resulting viral proteins and virions were negatively impacted by inactivation method and time. We outline the strengths and weaknesses of each method so that investigators might choose the one which best meets their research goals.
COVATOR: A Software for Chimeric Coronavirus Identification
Authors: Habib Peter T.
Published: November 2020

The term chimeric virus was not popular in the last decades. Recently, according to current sequencing efforts in discovering COVID-19 Secrets, the generated information assumed the presence of 6 Coronavirus main strains, but coronavirus diverges into hundreds of sub-strains. the bottleneck is the mutation rate. With two mutation/month, humanity will meet a new sub-strain every month. Tracking new sequenced viruses is urgently needed because of the pathogenic effect of the new substrains. here we introduce COVATOR, A user-friendly and python-based software that identifies viral chimerism. COVATOR aligns input genome and protein that has no known source, against genomes and protein with known source, then gives the user a graphical summary.