bluuebunny/crossref_metadata_2025 huggingface dataset:
Does an Ileoanal Anastomosis Decrease the Rate of Successful Pregnancy Compared With an Ileorectal Anastomosis? A National Study of 1491 Patients
Authors: Challine Alexandre , Voron Thibault , O’Connell Lauren , Chafai Najim , Debove Clotilde , Collard Maxime K. , Parc Yann , Lefèvre Jérémie H.
Published: July 2022

Objective:

Report the rate of successful pregnancy in a national cohort of women with either an ileal pouch anal (IPAA) or ileorectal (IRA) anastomosis constructed after colectomy for inflammatory bowel disease (IBD) or polyposis.

Background:

Fertility after IPAA is probably impaired. All available data are corroborated by only small sample size studies. It is not known whether construction of IPAA versus IRA influences the odds of subsequently achieving a successful pregnancy, especially with increased utilization of the laparoscopic approach.

Methods:

All women (age: 12–45 y) undergoing IRA or IPAA in France for polyposis or IBD, between 2010–2020, were included. A control population was defined as women aged from 12 to 45 years undergoing laparoscopic appendicectomy during the same period. The odds of successful pregnancy were studied using an adjusted survival analysis.

Results:

A total of 1491 women (IPAA=872, 58%; IRA=619, 42%) were included. A total of 220 deliveries (15%) occurred during the follow-up period of 71 months (39–100). After adjustment, the odds of successful pregnancy was not significantly associated with type of anastomosis (after IPAA: Hazard Ratio [HR]=0.79, 95% confidence interval=0.56–1.11, P=0.17). The laparoscopic approach increased the odds of achieving successful pregnancy (HR=1.79, 95% confidence interval=1.20–2.63, P=0.004). IRA and IPAA significantly impacted fertility when compared with the control population (P<0.001).

Conclusions:

In this large cohort study, total colectomy for polyposis or IBD was associated with reduced fertility compared with the general population. No difference in odds of achieving successful pregnancy was found between IRA and IPAA after adjustment. This analysis suggests laparoscopic surgery may be associated with greater likelihood of pregnancy.
The Timing of Acute and Late Complications Following Mastectomy and Implant-based Reconstruction
Authors: Jimenez Rachel B. , Packowski Kathryn , Horick Nora , Rosado Nikki , Chinta Sachin , Koh Daniel J. , Sobti Nikhil , Specht Michelle C. , Liao Eric C.
Published: July 2022

Background/Objective:

Implant-based breast reconstruction is a common plastic surgery procedure with well-documented clinical outcomes. Despite this, the natural history and timing of key complication endpoints are not well described. The goal of this study is to determine when patients are most likely to experience specific adverse events after implant-based reconstruction.

Methods:

Retrospective consecutive series of patients who received mastectomy and implant-based reconstruction over a 6-year period were included. Complications and unfavorable outcomes including hematoma, seroma, wound infection, skin flap necrosis, capsular contracture, implant rippling, and implant loss were identified. A time-to-event analysis was performed and Cox regression models identified patient and treatment characteristics associated with each outcome.

Results:

Of 1473 patients and 2434 total reconstructed breasts, 785 complications/unfavorable outcomes were identified. The 12-month cumulative incidence of hematoma was 1.4%, seroma: 4.3%, infection: 3.2%, skin flap necrosis: 3.9%, capsular contracture: 5.7%, implant rippling: 7.1%, and implant loss: 3.9%. In the analysis, 332/785 (42.3%) complications occurred within 60 days of surgery; 94% of hematomas, 85% of skin necrosis events, and 75% of seromas occurred during this period. Half of all infections and implant losses also occurred within 60 days. Of the remaining complications, 94% of capsular contractures and 93% of implant rippling occurred >60 days from surgery.

Conclusions:

Complications following mastectomy and implant-based reconstruction exhibit a discrete temporal distribution. These data represent the first comprehensive study of the timing of adverse events following implant-based reconstruction. These findings are immediately useful to guide postoperative care, follow-up, and clinical trial design.
Implementation of a Hepatocellular Carcinoma Screening Program for At-risk Patients Safety-Net Hospital: A Model for National Dissemination
Authors: Lee Rachel M. , Darby Rapheisha , Medin Caroline R. , Haser Grace C. , Mason Meredith C. , Miller Lesley S. , Staley Charles A. , Maithel Shishir K. , Russell Maria C.
Published: July 2022

Objective:

This study aimed to enhance hepatocellular carcinoma (HCC) screening to achieve earlier diagnosis of patients with hepatitis C (HCV) cirrhosis in our Safety-Net population.

Background:

Adherence to HCC screening guidelines at Safety-Net hospitals is poor. Only 23% of patients with HCC at our health system had a screening exam within 1-year of diagnosis and 46% presented with stage IV disease. HCV-induced cirrhosis remains the most common etiology of HCC (75%) in our patients.

Methods:

In the setting of an established HCV treatment clinic, an HCC screening quality improvement initiative was initiated for patients with stage 3 fibrosis or cirrhosis by transient elastography. The program consisted of semiannual imaging. Navigators scheduled imaging appointments and tracked compliance.

Results:

From April 2018 to April 2021, 318 patients were enrolled (mean age 61 years, 81% Black race, 38% uninsured). Adherence to screening was higher than previously reported: 94%, 75%, and 74% of patients completed their first, second, and third imaging tests. Twenty-two patients (7%) were diagnosed with HCC; 55% stage I and 14% stage IV. All patients were referred and 13 (59%) received treatment. Median time to receipt of treatment was 77 days (range, 32–282). Median overall survival for treated patients was 32 months.

Conclusions:

Implementation of an HCC screening program at a safety-net hospital is feasible and facilitated earlier diagnosis in this study. Patient navigation and tracking completion of imaging tests were key components of the program’s success. Next steps include expanding the program to additional at-risk populations.
Perpetuating Disparity
Authors: Cannon Robert M. , Anderson Douglas J. , MacLennan Paul , Orandi Babak J. , Sheikh Saulat , Kumar Vineeta , Hanaway Michael J. , Locke Jayme E.
Published: July 2022

Background:

The burden of end-stage kidney disease (ESKD) and kidney transplant rates vary significantly across the United States. This study aims to examine the mismatch between ESKD burden and kidney transplant rates from a perspective of spatial epidemiology.

Methods:

US Renal Data System data from 2015 to 2017 on incident ESKD and kidney transplants per 1000 incident ESKD cases was analyzed. Clustering of ESKD burden and kidney transplant rates at the county level was determined using local Moran’s I and correlated to county health scores. Higher percentile county health scores indicated worse overall community health.

Results:

Significant clusters of high-ESKD burden tended to coincide with clusters of low kidney transplant rates, and vice versa. The most common cluster type had high incident ESKD with low transplant rates (377 counties). Counties in these clusters had the lowest overall mean transplant rate (61.1), highest overall mean ESKD incidence (61.3), and highest mean county health scores percentile (80.9%, P<0.001 vs all other cluster types). By comparison, counties in clusters with low ESKD incidence and high transplant rates (n=359) had the highest mean transplant rate (110.6), the lowest mean ESKD incidence (28.9), and the lowest county health scores (20.2%). All comparisons to high-ESKD/low-transplant clusters were significant at P value <0.001.

Conclusion:

There was a significant mismatch between kidney transplant rates and ESKD burden, where areas with the greatest need had the lowest transplant rates. This pattern exacerbates pre-existing disparities, as disadvantaged high-ESKD regions already suffer from worse access to care and overall community health, as evidenced by the highest county health scores in the study.
Effect of Intraoperative Neuromonitoring on the Risks of Recurrent Laryngeal Nerve Injury During Thyroidectomy
Authors: Memeh Kelvin , Vaghaiwalla Tanaz , Keutgen Xavier , Angelos Peter
Published: July 2022

Objective:

To evaluate the relationship between the use intraoperative neuromonitoring (IONM) during thyroidectomy and the risk of recurrent laryngeal nerve (RLN) injury.

Background:

The role of IONM in reducing RLN injury during thyroidectomy remains controversial. Several studies on this topic apply conventional multivariable regression to adjust for confounding. However, estimates from this method may be biased due to model misspecification, especially with a rare outcome such as RLN injury.

Methods:

We used a pooled dataset created by linking the 2016–2019 National Surgical Quality Improvement Project General Participant User File with the corresponding Targeted-Thyroidectomy file. The primary outcome was RLN injury rates, and the secondary outcomes were operating time and postoperative length of stay. A doubly robust (DR) estimator, in the form of an inverse-probability-weighted regression adjustment model, was used to estimate the effect of the use of IONM on the risk of RLN injury. Sensitivity analyses was performed.

Results:

Twenty-four thousand three hundred seventy patients were evaluated, out of which 15,836 (70%) patients had IONM during thyroidectomy, and RLN injury occurred in 1498 (6.2%) cases. Rates of RLN injury increase with increasing age and BMI and are higher in patients with a cancer diagnosis, previous neck operation, total thyroidectomy, and node dissection. Doubly robust model suggests that the use of IONM was associated with a significant reduction in overall rate of RLN injury [risk ratio 0.77, confidence interval (CI), 0.68-0.87, P<0.001], and postoperative length of stay [−2.5 hours (CI, −4.18 to −0.81 h), P=0.004]. However, IONM use was associated with an increase in operating time [15.41 minutes (CI, 13.29-17.54 minutes), P<0.0001]. Sensitivity analyses revealed that our estimates are largely robust to confounding.

Conclusion:

In a balanced cohort of patients undergoing thyroidectomy from multiple sites and surgeons participating in National Surgical Quality Improvement Project, the use of IONM during thyroidectomy was associated with reduction in RLN injury.
A Statewide Approach to Reducing Re-excision Rates for Women With Breast-conserving Surgery
Authors: Schumacher Jessica R. , Lawson Elise H. , Kong Amanda L. , Weber Joseph J. , May Jeanette , Landercasper Jeffrey , Hanlon Bret , Marka Nicholas , Venkatesh Manasa , Cartmill Randi S. , Pavuluri Quamme Sudha , Nikolay Connor , Greenberg Caprice C.
Published: July 2022

Objective:

Test the effectiveness of benchmarked performance reports based on existing discharge data paired with a statewide intervention to implement evidence-based strategies on breast re-excision rates.

Background:

Breast-conserving surgery (BCS) is a common breast cancer surgery performed in a range of hospital settings. Studies have demonstrated variations in post-BCS re-excision rates, identifying it as a high-value improvement target.

Methods:

Wisconsin Hospital Association discharge data (2017–2019) were used to compare 60-day re-excision rates following BCS for breast cancer. The analysis estimated the difference in the average change preintervention to postintervention between Surgical Collaborative of Wisconsin (SCW) and nonparticipating hospitals using a logistic mixed-effects model with repeated measures, adjusting for age, payer, and hospital volume, including hospitals as random effects. The intervention included 5 collaborative meetings in 2018 to 2019 where surgeon champions shared guideline updates, best practices/challenges, and facilitated action planning. Confidential benchmarked performance reports were provided.

Results:

In 2017, there were 3692 breast procedures in SCW and 1279 in nonparticipating hospitals; hospital-level re-excision rates ranged from 5% to >50%. There was no statistically significant baseline difference in re-excision rates between SCW and nonparticipating hospitals (16.1% vs. 17.1%, P=0.47). Re-excision significantly decreased for SCW but not for nonparticipating hospitals (odds ratio=0.69, 95% confidence interval=0.52–0.91).

Conclusions:

Benchmarked performance reports and collaborative quality improvement can decrease post-BCS re-excisions, increase quality, and decrease costs. Our study demonstrates the effective use of administrative data as a platform for statewide quality collaboratives. Using existing data requires fewer resources and offers a new paradigm that promotes participation across practice settings.
Emotional Distress and Financial Toxicity in Younger Adult Patients Undergoing Oncologic Surgery
Authors: Tran Thuy B. , Malhotra Gautam , Razavi Marianne , Clark Karen , Loscalzo Matthew , Kruper Laura , Raoof Mustafa , Woo Yanghee , Trisal Vijay , Fong Yuman , Melstrom Laleh
Published: July 2022

Background:

There has been an alarming increase in the number of young adults (YA) diagnosed with cancer. The emotional, psychosocial, and financial distress experienced by newly diagnosed YA undergoing cancer surgery remains largely unknown.

Methods:

A validated biopsychosocial distress screening tool (SupportScreen) was administered to patients diagnosed with cancer before surgery between 2009 and 2017 in a National Cancer Institute Comprehensive Cancer Center. Patients were stratified into YA less than or equal to 45 years and older adults (OA) above 45 years. Descriptive statistics and logistic regression were used to analyze distress outcomes.

Results:

In total, 4297 patients were identified, with YA comprising 13.3% (n=573) of the cohort. YA reported higher emotional distress, including increased anxiety (33.8% vs 27.4%, P=0.002), greater fear of procedures (26.7% vs 22%, P=0.018), and difficulty managing emotions (26% vs 20.7%, P=0.006). YA struggled more frequently to manage work/school (29.5% vs 19.3%, P<0.001), finding resources (17.8% vs 11.8%, P<0.001), changes in physical appearance (22.2% vs 13.4%, P<0.001), fatigue (36% vs 27.3%, P<0.001), and ability to have children (18.4% vs 3%, P<0.001). Financial toxicity was significantly higher in the YA group (40.5% vs 28%, P<0.001). While income level was strongly protective against emotional distress and financial toxicity in OAs, it was less protective against the risk of financial toxicity in YA. Younger age was an independent predictor of financial toxicity in a model adjusted to income (odds ratio=1.52, P=0.020).

Conclusions:

YA in the prime of their personal and professional years of productivity require special attention when undergoing surgical evaluation for cancer. Resource allocation and counseling interventions should be integrated as part of their routine care to expedite their return to optimal physical and holistic health and mitigate psychosocial distress and financial toxicity.
COVID-19 Vaccination and the Timing of Surgery Following COVID-19 Infection
Authors: Le Sidney T. , Kipnis Patricia , Cohn Bradley , Liu Vincent X.
Published: July 2022

Objective:

To evaluate whether COVID-19 vaccination status or mode of anesthesia modified the temporal harms associated with surgery following coronavirus disease-2019 (COVID-19) infection.

Background:

Surgery shortly after COVID-19 infection is associated with higher rates of complications, leading to recommendations to delay surgery following COVID-19 infection when possible. However, prior studies were based on populations with low or no prevalence of vaccination.

Methods:

A retrospective cohort study of patients who underwent scheduled surgery in a health system from January 1, 2020 to February 28, 2022 (N=228,913) was performed. Patients were grouped by time of surgery relative to COVID-19 test positivity: 0 to 4 weeks after COVID-19 (“early post-COVID-19”), 4 to 8 weeks after COVID-19 (“mid post-COVID-19”), >8 weeks after COVID-19 (“late post-COVID-19”), surgery at least 30 days before subsequent COVID-19 (“pre-COVID-19”), and surgery with no prior or subsequent test positivity for COVID-19.

Results:

Among patients who were not fully vaccinated at the time of COVID-19 infection, the adjusted rate of perioperative complications for the early post-COVID-19 group was significantly higher than for the pre-COVID-19 group (relative risk: 1.55; P=0.05). No significantly higher risk was identified between these groups for patients who were fully vaccinated (0.66; P=1.00), or for patients who were not fully vaccinated and underwent surgery without general anesthesia (0.52; P=0.83).

Conclusions:

Surgery shortly following COVID-19 infection was not associated with higher risks among fully vaccinated patients or among patients who underwent surgery without general anesthesia. Further research will be valuable to understand additional factors that modify perioperative risks associated with prior COVID-19 infection.
Association Between Size of Dominant Candidate Lesion on Four-Dimensional CT and Four-Gland Hyperplasia among Patients with Primary Hyperparathyroidism
Authors: Broekhuis Jordan M , Chaves Natalia , Chen Hao Wei , Cloonan Daniel J , Sacks Barry A , James Benjamin C
Published: July 2022

BACKGROUND:

Four-dimensional (4D) CT localization allows minimally invasive parathyroidectomy as treatment for primary hyperparathyroidism (PHPT), but false positive localization is frequent. We sought to characterize the ability of 4D CT to predict four-gland hyperplasia (HP) based on the size of candidate lesions.

STUDY DESIGN:

We retrospectively analyzed patients with PHPT who underwent 4D CT imaging and parathyroidectomy between 2014 and 2020 from a prospectively collected institutional database. The cohort was stratified into two groups, HP vs single adenoma (SA) and double adenoma (DA), based on operative findings and pathology. Logistic regression models assessed the association between the greatest diameter of the dominant candidate lesion on 4D CT and the outcomes of four-gland hyperplasia vs SA and DA.

RESULTS:

Among a cohort of 240 patients, 41 were found to have HP, and 199 had adenomas (SA = 155, DA = 44). Patients with HP were less likely to have a preoperative calcium level greater than 1 mg/dL above the upper limit of normal compared with patients with adenomas (63% vs 81%, p = 0.02) and more likely to report symptoms (61% vs 43%, p = 0.04). After adjusting for BMI, we found an estimated 13% reduction in odds of HP for every 1-mm increase in the greatest diameter of dominant candidate lesions identified on 4D CT scan (odds ratio 0.87, 95% CI 0.78 to 0.96, p = 0.009).

CONCLUSIONS:

A smaller size of the dominant lesion on 4D CT scan is associated with an increased risk of HP in PHPT. Use of 4D CT imaging localization may provide evidence for differentiating HP from adenomas.
Artificial Intelligence and Surgery: Ethical Dilemmas and Open Issues
Authors: Cobianchi Lorenzo , Verde Juan Manuel , Loftus Tyler J , Piccolo Daniele , Dal Mas Francesca , Mascagni Pietro , Garcia Vazquez Alain , Ansaloni Luca , Marseglia Giuseppe Roberto , Massaro Maurizio , Gallix Benoit , Padoy Nicolas , Peter Angelos , Kaafarani Haytham M
Published: July 2022

BACKGROUND:

Artificial intelligence (AI) applications aiming to support surgical decision-making processes are generating novel threats to ethical surgical care. To understand and address these threats, we summarize the main ethical issues that may arise from applying AI to surgery, starting from the Ethics Guidelines for Trustworthy Artificial Intelligence framework recently promoted by the European Commission.

STUDY DESIGN:

A modified Delphi process has been employed to achieve expert consensus.

RESULTS:

The main ethical issues that arise from applying AI to surgery, described in detail here, relate to human agency, accountability for errors, technical robustness, privacy and data governance, transparency, diversity, non-discrimination, and fairness. It may be possible to address many of these ethical issues by expanding the breadth of surgical AI research to focus on implementation science. The potential for AI to disrupt surgical practice suggests that formal digital health education is becoming increasingly important for surgeons and surgical trainees.

CONCLUSIONS:

A multidisciplinary focus on implementation science and digital health education is desirable to balance opportunities offered by emerging AI technologies and respect for the ethical principles of a patient-centric philosophy.
Evaluating the Thematic Nature of Microaggression among Racial and Ethnic Minority Surgeons
Authors: Appah-Sampong Abena , Zakrison Tanya , Vela Monica , Saunders Milda , Zhang Lindsey , Dorsey Chelsea
Published: July 2022

BACKGROUND:

It is well documented that surgeons who identify as racial and ethnic minorities experience discrimination while navigating the surgical environment. There is evidence to suggest that the most prevalent form of discrimination experienced is microaggressions. This study sought to identify common microaggressions experienced in the surgical workplace by racial and ethnic minority surgeons with the use of a validated scale.

METHODS:

A one-time, deidentified survey was administered to surgeons who identified as a racial and ethnic minority via email. The survey included demographic questions and a shortened version of the Racial Microaggressions Scale, a validated 32-item scale developed to measure microaggressions in everyday life. Subscale means were calculated and compared using sample t-tests along with an analysis of variance.

RESULTS:

A total of 185 surgeons completed the survey with 166 included in the final analysis (97 male-identifying, 67 female-identifying). Significantly different microaggression experiences between race and ethnicity were found on the environmental (p < 0.001), foreigner/not belonging (p ≤ 0.001), low achieving/undesirable (p < 0.001), criminality (p < 0.001), and invisibility (p < 0.001) subscales with higher scores denoting more frequent experiences. Black and African American surgeons scored higher than Asian and Asian American and Hispanic and Latino surgeons on the low achieving/undesirable subscale (1.7 vs 0.9 and 1.2, respectively) and the invisibility subscale (1.5 vs 0.8 and 0.8, respectively). In addition, Asian and Asian American and Hispanic and Latino surgeons scored significantly higher on the foreigner/not belonging subscale compared with Black and African American surgeons (1.6 and 1.6 vs 0.9, respectively).

CONCLUSIONS:

The current study suggests that surgeons who identified as a racial and ethnic minority experience microaggressions in various ways. Understanding the specific experience of racial and ethnic minority surgeons is important as the surgical workplace strives to create more inclusive environments by acknowledging the lived experience of its diverse workforce.
Upregulation of Activation Induced Cell Markers (AIM) among Severe COVID-19 patients in Bangladesh
Authors: Bhuiyan Taufiqur Rahman , Banna Hasan Al , Kaisar M Hasanul , Karmakar Polash Chandra , Hakim Al , Akter Afroza , Ahmed Tasnuva , Tauheed Imam , Islam Shaumik , Hasnat Mohammad Abul , Sumon Mostafa Aziz , Rashed Asif , Ghosh Shuvro , Clemens John D , Banu Sayera , Shirin Tahmina , Weiskopf Daniela , Sette Alessandro , Chowdhury Fahima , Qadri Firdausi
Published: July 2022

COVID-19 caused by SARS-CoV-2 can develop the disease with different degree of clinical severity including fatality. In addition to antibody responses the antigen specific T cells may play a critical role in defining this protective immune response against this virus. As a part of a longitudinal cohort study in Bangladesh to investigate B and T cell specific immune responses, we sought to evaluate the activation induced cell marker (AIM) and the status of different immune cell subsets during infection. A total of 115 participants were analyzed in this study which included participants with asymptomatic, mild, moderate and severe clinical symptoms. In addition, healthy controls (19 in each group) were analysed. Specimens from participants collected during the pre-pandemic period were also analyzed (n=10). Follow-up visits were conducted on day 7, 14, and 28 for all the cases since the enrollment (day 1). In this study 10 participants among the moderate and severe cases expired during the course of follow up. We observed a decrease in mucosa associated invariant T (MAIT) cell frequency on the initial days (day 1 and day 7) in comparison to later days of the COVID-19 infection. However, natural killer (NK) cells were found to be elevated in symptomatic patients just after the onset of disease compared to both asymptomatic patients and healthy individuals. Moreover, we found AIM+ (both OX40+ CD137+ and OX40+ CD40L+) CD4+ T cells to show significant increase in moderate and severe COVID-19 patients in response to SARS-CoV-2 peptides (specially spike peptide) compared to prepandemic controls, who are unexposed to SARS-CoV-2. Notably, we did not observe any significant difference in the CD8+ AIM markers (CD137+ CD69+), which indicates the exhaustion of CD8+ T cells during COVID-19 infection. These findings suggest that the patients who recovered from moderate and severe COVID-19 were able to mount a strong CD4+ T cell response against shared viral determinants that ultimately induced the T cells to mount further immune responses to SARS-CoV-2.
Effect of Vitamin D3 supplementation vs. dietary-hygienic measures on SARS-COV-2 infection rates in hospital workers with 25-hydroxyvitamin D3 [25(OH)D3] levels ≥20 ng/mL
Authors: Romero-Ibarguengoitia Maria Elena , Gutiérrez-González Dalia , Cantú-López Carlos , Sanz-Sánchez Miguel Angel , González-Cantú Arnulfo
Published: July 2022

Background

There is scant information on the effect of supplementation with vitamin D3 in SARS-COV-2 infection cases when patient 25-hydroxyvitamin D3 [25(OH)D3] levels are between 20-100ng/mL. Our aim was to evaluate the effect of supplementation with vitamin D3 vs. dietary-hygienic measures on the SARS-COV-2 infection rate in participants with serum 25(OH)D3 levels ≥20ng/mL.

Methods

We invited hospital workers with 25(OH)D3 levels between 20-100 ng/mL and no previous SARS-COV-2 infection; they were randomized as follows: treatment options were a) vitamin D3 supplementation (52,000 IU monthly, G1) or b) dietary-hygienic measures (G2). We conducted a 3- to 6-month follow-up of SARS-COV-2 infections. Participants with 25(OH)D3 levels <20 ng/mL were also analyzed. We divided these latter participants depending on whether they were supplemented (G3) or not (G4).

Results

We analyzed 198 participants, with an average age of 44.4 (SD 9) years, and 130 (65.7%) were women. G1 had less cases of SARS-COV-2 infection than G2 after a follow-up of 3- to 6-months (p<0.05). There were no differences between G3 and G4 at the 3- and 6-month follow-up cutoff points (p>0.05). Using mixed effect Cox regression analysis in 164 participants that completed six months of follow-up, vitamin D3 supplementation appeared to act as a protective factor against SARS-COV-2 infection (HR 0.21, p=0.008) in G1 and G2. None of the participants treated with the supplementation doses had serum 25(OH)D3 levels > 100ng/mL.

Conclusion

Vitamin D3 supplementation in participants with 25(OH)D3 levels between 20-100 ng/mL have a lower rate of SARS-COV-2 infection in comparison with the use of dietary-hygienic measures at six months follow-up.
Health care utilization of fine-scale identity by descent clusters in a Los Angeles biobank
Authors: Caggiano Christa , Boudaie Arya , Shemirani Ruhollah , Petter Ella , Chiu Alec , Johnson Ruth , Ercelen Defne , Pasaniuc Bogdan , Kenny Eimear , Shortt Jonathan , Gignoux Chris , Balliu Brunilda , Arboleda Valerie , Belbin Gillian , Zaitlen Noah
Published: July 2022

1

An individual’s disease risk is affected by the populations that they belong to, due to shared genetics and shared environment. The study of fine-scale populations in clinical care will be important for reducing health disparities and for developing personalized treatments. In this work, we developed a novel health monitoring system, which leverages biobank data and electronic medical records from over 40,000 UCLA patients. Using identity by descent (IBD), we analyzed one type of fine-scale population, an IBD cluster. In total, we identified 376 IBD clusters, including clusters characterized by the presence of many significantly understudied communities, such as Lebanese Christians, Iranian Jews, Armenians, and Gujaratis. Our analyses identified thousands of novel associations between IBD clusters and clinical diagnoses, physician offices, utilization of specific medical specialties, pathogenic allele frequencies, and changes in diagnosis frequency over time. To enhance the impact of the research and engage the broader community, we provide a web portal to query our results:www.ibd.la
Platinum vs non-platinum chemotherapy for platinum-resistant ovarian cancer: a systematic review and meta-analysis
Authors: Rumyantsev Alexey , Tyulyandina Alexandra , Fedyanin Mikhail , Pokataev Ilya , Glazkova Elena , Tjulandin Sergey
Published: July 2022

Background

recurrent ovarian cancer (OC) patients with platinum-free interval (PFI) <6 mo. are usually considered platinum-resistant and treated with non-platinum based chemotherapy. However, this was never confirmed in proper-conducted randomized trials.

Methods

we queried the PubMed database for all full-text articles and abstracts on the treatment of patients with platinum-resistant ovarian cancer (PROC) in 01/01/2000-01/06/2019 timeframe. The PRISMA tool was used to ensure transparent reporting of the results. Inclusion criteria were: 1) morphologically confirmed epithelial ovarian cancer; 2) recurrent disease within 6 months after completion of platinum-based chemotherapy; 3) treatment with platinum- or non-platinum chemotherapy with agents that are routinely used for OC; 4) no concomitant therapy with targeted or investigational agents or non-platinum doublets; 5) defined response rate (RR) and assessment criteria. Proportion meta-analysis (random-effect model) and beta-regression were conducted to assess the impact of platinum agents on response rate as well as significance of other variables. In the beta-regression model response rate was a dependent variable, while platinum agents (yes or no), used non-platinum drugs and method of response assessment were independent variables. Statistical analysis was dose with meta, metafor and betareg packages of R software.

Results

we identified 7156 articles and screened them for title and abstract, 157 studies for further analysis. Overall, 6327 patients were included in the analysis, efficacy of non-platinum- and platinum-based therapy was assessed in 113 (n = 5272) and 44 (n = 1055) trials respectively. In meta-proportion random-effect model RR among patients treated with platinum-based and non-platinum chemotherapy RR was 36% (95% CI 30-41; I2 = 62%) and 16% (95% CI 14-19; I2=70%) respectively. For sensitivity analysis various regression models were made with different subsets of the trials and additional variables (including year of the trial, percentage of serous subtype of OC and median of prior therapy lines). Platinum was the strongest predictor of response in every developed model.

Conclusion

this meta-analysis shows that patients with ‘platinum-resistant’ ovarian carcinoma may derive significant benefit from reintroduction of platinum agents. These results support recent ESMO-ESGO consensus on treatment of recurrent ovarian cancer.
Evolutionary innovation through transcription factor promiscuity in microbes is constrained by pre-existing gene regulatory network architecture
Authors: Shepherd Matthew J. , Pierce Aidan P. , Taylor Tiffany B.
Published: July 2022

The survival of a population during environmental shifts depends on whether the rate of phenotypic adaptation keeps up with the rate of changing conditions. A common way to achieve this is via change to gene regulatory network (GRN) connections – known as rewiring – that facilitate novel interactions and innovation of transcription factors. To understand the success of rapidly adapting organisms, we therefore need to determine the rules that create and constrain opportunities for GRN rewiring.

Here, using an experimental microbial model system we reveal a hierarchy among transcription factors that are rewired to rescue lost function, with alternative rewiring pathways only unmasked after the preferred pathway is eliminated. We identify three key properties - high activation, high expression, and pre-existing low-level affinity for novel target genes – that facilitate transcription factor innovation via gain of functional promiscuity. Ease of acquiring these properties is constrained by pre- existing GRN architecture, which was overcome in our experimental system by both targeted and global network alterations. This work reveals the key properties that determine transcription factor evolvability, and as such, the evolution of GRNs.
GEARS: Predicting transcriptional outcomes of novel multi-gene perturbations
Authors: Roohani Yusuf , Huang Kexin , Leskovec Jure
Published: July 2022

Cellular response to genetic perturbation is central to numerous biomedical applications from identifying genetic interactions involved in cancer to methods for regenerative medicine. However, the combinatorial explosion in the number of possible multi-gene perturbations severely limits experimental interrogation. Here, we present GEARS, a method that can predict transcriptional response to both single and multi-gene perturbations using single-cell RNA-sequencing data from perturbational screens. GEARS is uniquely able to predict outcomes of perturbing combinations consisting of novel genes that were never experimentally perturbed by leveraging geometric deep learning and a knowledge graph of gene-gene relationships. GEARS has higher precision than existing approaches in predicting five distinct genetic interaction subtypes and can identify the strongest interactions more than twice as well as prior approaches. Overall, GEARS can discover novel phenotypic outcomes to multi-gene perturbations and can thus guide the design of perturbational experiments.
Microstructural and crystallographic evolution of palaeognath (Aves) eggshells
Authors: Choi Seung , Hauber Mark E , Legendre Lucas J , Kim Noe-Heon , Lee Yuong-Nam , Varricchio David J
Published: July 2022

The avian palaeognath phylogeny has been recently revised significantly due to the advancement of genome-wide comparative analyses and provides the opportunity to trace the evolution of the microstructure and crystallography of modern dinosaur eggshells. Here, eggshells of all major clades of Palaeognathae (including extinct taxa) and selected eggshells of Neognathae and non-avian dinosaurs are analysed with electron backscatter diffraction. Our results show the detailed microstructures and crystallographies of (previously) loosely categorized ostrich-, rhea-, and tinamou-style morphotypes of palaeognath eggshells. All rhea-style eggshell appears homologous, while respective ostrich-style and tinamou-style morphotypes are best interpreted as homoplastic morphologies (independently acquired). Ancestral state reconstruction and parsimony analysis additionally show that rhea-style eggshell represents the ancestral state of palaeognath eggshells both in microstructure and crystallography. The ornithological and palaeontological implications of the current study are not only helpful for the understanding of evolution of modern and extinct dinosaur eggshells, but also aid other disciplines where palaeognath eggshells provide useful archive for comparative contrasts (e.g. palaeoenvironmental reconstructions, geochronology, and zooarchaeology).
Improved detection of genetic effects on promoter usage with augmented transcript annotations
Authors: Vija Andreas , Alasoo Kaur
Published: July 2022

Disease-associated non-coding variants can modulate their target genes by disrupting multiple mechanisms, including regulating total gene expression level, splicing, alternative polyadenylation or promoter usage. Quantifying promoter usage from standard RNA sequencing data is challenging due to incomplete reference transcriptome annotations and low read coverage observed at the ends of transcripts. We previously developed the txrevise tool (https://github.com/kauralasoo/txrevise) to quantify promoter usage events from RNA-seq data using reference transcriptome annotations. Here, we augment the txrevise promoter event annotations with experimentally identified Cap Analysis of Gene Expression (CAGE) promoters from the FANTOM5 project. Applying the new annotations to RNA-seq data from 358 individuals, we found that augmented promoter event annotations increased the power to detect promoter usage quantitative trait loci (puQTLs) by ~30%. However, concordance between puQTLs inferred from RNA-seq data and those directly measured using CAGE remained low, suggesting that additional experimental and computational improvements are needed to capture the full range of regulatory effects of non-coding variants.
Neonatal hyperoxia induces sex-dependent pulmonary cellular and transcriptomic changes in an experimental mouse model of bronchopulmonary dysplasia
Authors: Xia Sheng , Vila Ellis Lisandra , Winkley Konner , Menden Heather , Mabry Sherry M. , Louiselle Daniel , Gibson Margaret , Grundberg Elin , Chen Jichao , Sampath Venkatesh
Published: July 2022

Hyperoxia (HOX) disrupts lung development in mice and causes bronchopulmonary dysplasia (BPD) in neonates. To investigate sex-dependent molecular and cellular programming involved in HOX, we surveyed the mouse lung using single cell RNA sequencing (scRNA-seq), and validated our findings in human neonatal lung cells in vitro. HOX-induced inflammation in alveolar type (AT) 2 cells gave rise to damage associated transient progenitors (DATP). It also induced a new subpopulation of AT1 cells with reduced expression of growth factors normally secreted by AT1 cells, but increased mitochondrial gene expression. Female alveolar epithelial cells had less EMT and pulmonary fibrosis signaling in HOX. In the endothelium, expansion of Car4+ EC (Cap2) was seen in HOX along with an emergent subpopulation of Cap2 with repressed VEGF signaling. This regenerative response was increased in females exposed to HOX. Mesenchymal cells had inflammatory signatures in HOX, with a new distal interstitial fibroblast subcluster characterized by repressed lipid biosynthesis and a transcriptomic signature resembling myofibroblasts. HOX-induced gene expression signatures in human neonatal fibroblasts and alveolar epithelial cells in vitro resembled mouse scRNA-seq data. These findings suggest that neonatal exposure to HOX programs distinct sex-specific stem cell progenitor and cellular reparative responses that underpin lung remodeling in BPD.
Genomic selection performs as effectively as phenotypic selection for increasing seed yield in soybean
Authors: Bandillo Nonoy B. , Jarquin Diego , Posadas Luis G. , Lorenz Aaron J. , Graef George L.
Published: July 2022

Increasing the rate of genetic gain for seed yield remains the primary breeding objective in both public and private soybean breeding programs. Genomic selection (GS) has the potential to accelerate the rate of genetic gain for soybean seed yield. To date, limited studies have empirically validated accuracy of GS and compared to phenotypic selection (PS), and none has been done for soybean breeding. This study conducted the first empirical validation of GS for increasing seed yield using over 1,500 lines and over 7 years (2010-2016) of replicated experiments in the University of Nebraska soybean breeding program. The study was designed to capture the varying genetic relatedness of the training population to three validation sets: two large bi-parental populations (TBP-1 and TBP-2), and a large validation set comprised of 457 pre-selected advanced lines derived from 45 bi-parental populations in the variety development program (TMP). We found that prediction accuracy (0.54) from our validation experiments was competitive with what we obtained from a series of cross-validation experiments (0.64). Both GS and PS were more effective for increasing population mean performance with similar realized gain but significantly greater than random selection (RS). We found a selection advantage of GS over PS where higher genetic gain and identification of top-performing lines was maximized at higher selection stringency from 10 to 20% selected proportion. GS led to at least 2% increase in the mean genetic similarity vs. PS and RS, potentially causing a minimal loss of genetic diversity. We showed that loss of genetic variance in the GS set was presumably due to a significant shift on allelic frequencies towards the extremes. Across all loci, an average increase of 0.04 in allelic frequency in the GS set was observed after selection, which is about 5% higher than the base population when no selection was made. Overall, we demonstrate that GS performed as effectively as PS, and the implementation of GS in a public soybean breeding program should be warranted mainly for reducing breeding cycle time and lowering cost per unit gain.
Jump-Drop Adjusted Prediction of Cumulative Infected Cases using the Modified SIS Model
Authors: Mohta Rashi , Prathapani Sravya , Ghosh Palash
Published: July 2022

Accurate prediction of cumulative COVID-19 infected cases is essential for effectively managing the limited healthcare resources, specifically in India. Historically, epidemiological models have helped control such epidemics. Those models need accurate past data to predict for future. However, for various reasons, we observe sudden drops and jumps in the number of daily reported COVID-19 infected cases on some days, not aligned with the overall trend. If we incorporate those observations in the training data, the model's prediction accuracy may worsen, as they do not capture the correct trend in the training data. But it is not straightforward for the existing epidemiological models to decide a specific day as a sudden drop or jump. We propose an algorithm that automatically determines any drop or jump days in this work. Then, based on the overall trend in the data, we adjust the number of daily infected cases on those days and decide on the training data based on the adjusted observations. We have applied the proposed algorithm in a recently proposed modified Susceptible-Infected-Susceptible (SIS) to show that adjusted training data gives better prediction accuracy when jump and drop exist in the training data.
Comparison of Very Short Answer Questions and Multiple Choice Questions in Medical Students: Reliability, Discrimination, Acceptability and Effect on Knowledge Retention
Authors: Janse Roemer J. , van Wijk Elise V. , Ruijter Bastian N. , Rohling Jos H.T. , van der Kraan Jolein , Crobach Stijn , de Jonge Mario , de Beaufort Arnout Jan , Dekker Friedo W. , Langers Alexandra M.J.
Published: July 2022

Introduction

Multiple choice questions (MCQs) offer high reliability and easy machine-marking, but allow for cueing and stimulate recognition-based learning. Very short answer questions (VSAQs) may circumvent these limitations. We investigated VSAQ reliability, discriminative capability, acceptability, and knowledge retention compared to MCQs.

Methods

Dutch undergraduate medical students (n=375) were randomised to a formative exam with VSAQs first and MCQs second or vice versa in two courses, to determine reliability and discrimination. Next, acceptability (i.e., VSAQ review time) was determined in the summative exam. Knowledge retention at 2 and 5 months was determined by comparing score increase on the three-monthly progress test (PT) between students tested with VSAQs and students from previous years tested without VSAQs.

Results

Reliability (Cronbach’s α) was 0.74 for VSAQs and 0.57 for MCQs in one course. In the other course, Cronbach’s α was 0.87 for VSAQs and 0.83 for MCQs. Discrimination (Rir) was 0.27 vs. 0.17 and 0.43 vs. 0.39 for VSAQs vs. MCQs, respectively. Reviewing time of one VSAQ for the entire student cohort was ±2 minutes on average. No clear effect on knowledge retention after 2 and 5 months was observed.

Discussion

We found increased reliability and discrimination of VSAQs compared to MCQs. Reviewing time of VSAQs was acceptable. The association with knowledge retention was unclear in our study. This study supports and extends positive results of previous studies on VSAQs regarding reliability, discriminative capability, and acceptability in Dutch undergraduate medical students.
RAFTS: A graphical tool to guide Flux Simulator transcriptome simulation for method development in de novo transcriptome assembly from short reads
Authors: Doering Matthew , Stout Jake M.
Published: July 2022

Due to complexity of RNA transcripts expressed in any given cell or tissue, the assembly of de novo transcriptomes still represents a computational challenge when compared to genome assemblies. A number of modern transcriptome assembly algorithms have been developed to meet this challenge, and each of them have their own strengths and weaknesses dependent on the transcript abundance and complexity of the biological sample that is sequenced. As such, we are seeking to develop a transcriptome assembly pipeline in which multiple transcriptomes are generated, merged, and then redundancies are filtered out to produce a final transcriptome that should contain full length sequences of all transcripts. However, it is almost impossible to evaluate the efficacies of such novel assembly pipelines using short read sequencing data derived from biological samples due to not knowing a priori the transcript abundance and complexity. Thus, to test our pipelines we developed RAFTS. This tool is used to generate simulated short read sequencing datasets using annotated genomic data from model species.
Epigenetic markers of adverse lifestyle identified among night shift workers
Authors: Hulls Paige M. , McCartney Daniel L. , Bao Yanchun , Walker Rosie M. , de Vocht Frank , Martin Richard M. , Relton Caroline L. , Evans Kathryn L. , Kumari Meena , Marioni Riccardo E. , Richmond Rebecca C.
Published: July 2022

Background

Epigenetic changes in the form of DNA methylation (DNAm) may act as biological markers of risk factors or adverse health states. We investigated associations between night shift work and established DNAm predictors of lifestyle, and compared them with those observed between night shift work and self-reported or conventionally-measured phenotypes.

Methods

In two cohort studies, Generation Scotland (GS) (n=7,028) and Understanding Society (UKHLS) (n=1,175), we evaluated associations between night shift work and four lifestyle factors (body mass index, smoking, alcohol, education) using both conventionally-measured phenotypes and DNA methylation-based scores proxying the phenotypes. DNA methylation-based measures of biological ageing were also generated using six established “epigenetic clocks”. Meta-analysis of GS and UKHLS results was conducted using inverse-variance weighted fixed effects.

Results

Night shift work was associated with higher BMI (0.79; 95%CI 0.02, 1.56; p=0.04) and lower education (-0.18; -0.30, -0.07; p=0.002). There was weak evidence of association between night shift work and DNAm scores for smoking (0.06, -0.03, 0.15; p=0.18) and education (-0.24; -0.49, 0.01; p=0.06) in fully adjusted models. Two of the epigenetic age measures demonstrated higher age acceleration among night shift workers (0.80; 0.42, 1.18; p<0.001 for GrimAge and 0.46; 0.00, 0.92; p=0.05 for PhenoAge).

Conclusions

Night shift work is associated with phenotypic and DNAm-based measures of lower education. Night shift work was also related to DNAm predictors of smoking and ageing.