bluuebunny/crossref_metadata_2025 huggingface dataset:
Linking Technology to Address the Social and Medical Determinants of Health for Safe Medicines Use
Authors: Woosley Raymond L. , Simmons June , Sefilyan Ester M. , Atkins Sandy , Black Kristin , Read William A.
Published: June 2021

Objectives

Both social and medical factors can negatively affect health outcomes, especially in vulnerable populations. To address these 2 types of factors in a postdischarge population, 2 nonprofit organizations collaborated to combine their novel decision support programs and address the question: Could combined programs have greater potential for improved health outcomes?

Methods

HomeMeds, a social health program in which trained social services staff make home visits to vulnerable clients, was combined with MedSafety Scan, a medical health, clinical decision support tool. Data captured in the home visits were entered into the HomeMeds and MedSafety Scan programs to detect those patients at the greatest risk of adverse health outcomes because of medications.

Results

Patients (n = 108; mean age, 77 years; multiple comorbidities and LACE+ (length of stay, acuity, comorbidities, emergency department visits [hospital index]; score >29) received a postdischarge home visit by trained social services staff. The number of drugs reported as being taken was 10.4 ± 5.1 (range, 1–26), which was less than prescribed at discharge in 62% of patients (range, 1–8). Both programs detected a serious risk of medication-induced harm, mostly from different causes such as drug-drug interactions or for use not recommended in the elderly.

Conclusions

Combined analysis of data from 2 novel decision support programs yielded complementary findings that together address both medical and social determinants of health. These have the potential to reduce medication-induced harm, costly rehospitalization, and/or emergency department visits and support the further evaluation of this combined approach in other vulnerable populations such as the seriously mentally ill, frail, those confined to home, opioid dependent, or otherwise impaired.
Which Health Impacts of Medical Device Adverse Event Should Be Reported Immediately in Korea?
Authors: Choi Sooin , Choi Soo Jeong , Kim Jin Kuk , Yoon Chiho , Nam Ki Chang , Kwon Bum Sun , Lee You Kyoung
Published: June 2021

Objective

Immediate medical device adverse event (MDAE) reporting indications of Korea include death, life-threatening, hospitalization (initial or prolonged), disability or permanent damage, and congenital malformation or abnormalities. With the advent of new codes from the International Medical Device Regulators Forum, a study was undertaken to explore the applicability of health impact codes as immediate MDAE reporting indications in the Republic of Korea.

Method

This domestic cross-sectional survey study was conducted for members from Medical Device Safety Information Monitoring Center in November 2019. For the annex F (health impact) codes defining health impact of an MDAE, we checked whether each code matched with the current indication and asked experts whether they agreed with each code as an indication of immediate reporting. Consensus was reached when ≥70% of experts agreed.

Results

A total of 28 experts from 19 centers responded to the survey. Of a total of 64 codes, 29 matched with the current indication. However, in an expert survey, 17 of 29 codes were not agreed for immediate reporting and 5 codes were found to be unmatched codes. For these 5 codes, experts agreed that they would need reporting immediately. Finally, only 17 codes achieved consensus for immediate reporting.

Conclusions

There is a discrepancy between the code matched to the current immediate MDAE reporting indication and experts’ consensus. Sufficient discussion and agreement would be needed to apply health impact codes for immediate reporting.
Safety and Gadolinium Distribution of the New High-Relaxivity Gadolinium Chelate Gadopiclenol in a Rat Model of Severe Renal Failure
Authors: Fretellier Nathalie , Rasschaert Marlène , Bocanegra Julien , Robert Philippe , Factor Cécile , Seron Aymeric , Idée Jean-Marc , Corot Claire
Published: June 2021

Objective

The aim of this study was to investigate the toxicological profile of gadopiclenol, a new high-relaxivity macrocyclic gadolinium-based contrast agent (GBCA), in renally impaired rats, in comparison with 2 other macrocyclic GBCAs, gadoterate meglumine and gadobutrol, and 1 linear and nonionic GBCA, gadodiamide.

Methods

Renal failure was induced by adding 0.75% wt/wt adenine to the diet for 3 weeks. During the second week of adenine-enriched diet, the animals (n = 8/group × 5 groups) received 5 consecutive intravenous injections of GBCA at 2.5 mmol/kg per injection, resulting in a cumulative dose of 12.5 mmol/kg or saline followed by a 3-week treatment-free period after the last injection. The total (elemental) gadolinium (Gd) concentration in different tissues (brain, cerebellum, femoral epiphysis, liver, skin, heart, kidney, spleen, plasma, urine, and feces) was measured by inductively coupled plasma mass spectrometry. Transmission electron microscopy (and electron energy loss spectroscopy analysis of metallic deposits) was used to investigate the presence and localization of Gd deposits in the skin. Relaxometry was used to evaluate the presence of dissociated Gd in the skin, liver, and bone. Skin histopathology was performed to investigate the presence of nephrogenic systemic fibrosis–like lesions.

Results

Gadodiamide administrations were associated with high morbidity-mortality but also with macroscopic and microscopic skin lesions in renally impaired rats. No such effects were observed with gadopiclenol, gadoterate, or gadobutrol. Overall, elemental Gd concentrations were significantly higher in gadodiamide-treated rats than in rats treated with the other GBCAs for all tissues except the liver (where no significant difference was found with gadopiclenol) and the kidney and the heart (where statistically similar Gd concentrations were observed for all GBCAs). No plasma biochemical abnormalities were observed with gadopiclenol or the control GBCAs. Histopathology revealed a normal skin structure in the rats treated with gadopiclenol, gadoterate, and gadobutrol, contrary to those treated with gadodiamide. No evidence of Gd deposits on collagen fibers and inclusions in fibroblasts was found with gadopiclenol and its macrocyclic controls, unlike with gadodiamide. Animals of all test groups had Gd-positive lysosomal inclusions in the dermal macrophages. However, the textures differed for the different products (speckled texture for gadodiamide and rough-textured appearance for the 2 tested macrocyclic GBCAs).

Conclusions

No evidence of biochemical toxicity or pathological abnormalities of the skin was observed, and similar to other macrocyclic GBCAs, gadoterate and gadobutrol, tissue retention of Gd was found to be low (except in the liver) in renally impaired rats treated with the new high-relaxivity GBCA gadopiclenol.
Etomidate Attenuates the Ferroptosis in Myocardial Ischemia/Reperfusion Rat Model via Nrf2/HO-1 Pathway
Authors: Lv Zhenqian , Wang Feng’e , Zhang Xingfeng , Zhang Xiting , Zhang Jing , Liu Ran
Published: June 2021

Background:

Ferroptosis has been found to play an important role in myocardial ischemia reperfusion (MIR) injury (MIRI). This study aimed to explore whether the improvement effect of Etomidate (Eto) on MIRI was related to ferroptosis.

Methods:

The MIRI rats were constructed using left anterior descending artery occlusion for 30 min followed by reperfusion for 3 h. The Eto post-conditioning was performed by Eto administration at the beginning of the reperfusion. For rescue experiments, MIRI rats were pretreated with ferroptosis inducer erastin or Nrf2 inhibitor ML385 intraperitoneally 1 h prior to MIR surgery.

Results:

Eto mitigated cardiac dysfunction and myocardium damage, as well as the release of creatine kinase and lactate dehydrogenase caused by ischemia/reperfusion (IR). Additionally, Eto reduced the expression of myocardial fibrosis-related proteins (collagen II and α-smooth muscle actin) and the secretion of inflammatory factors (IL-6, IL-1β, and TNF-α) in MIRI rats. Also, Eto inhibited IR-induced ferroptosis in myocardium, including reducing superoxide dismutase content, glutathione activity, and glutathione peroxidase 4 expression, while increasing the levels of malondialdehyde and iron and Acyl-CoA synthetase long-chain family member 4. Moreover, the inhibition of Eto on IR-induced myocardial fibrosis and inflammation could be eliminated by erastin. The up-regulation of Nrf2 and HO-1 protein expression, and the nuclear translocation of Nrf2 induced by Eto in the myocardial tissues of MIRI rats, could be prevented by erastin. Besides, ML385 eliminated the inhibition of Eto on ferroptosis induced by MIR.

Conclusions:

Eto attenuated the myocardial injury by inhibiting IR-induced ferroptosis via Nrf2 pathway, which may provide a new idea for clinical reperfusion therapy.
Reviewing the Reviewers Potential Financial Conflicts of Interest in Editorial Boards of Surgery Journals
Authors: Elsolh Basheer , Brar Amanpreet , Gyawali Bishal , Patel Sunil V.
Published: June 2021

Objective:

To assess the prevalence, magnitude, and disclosure status of industry funding in editorial boards of surgery journals.

Summary of Background Data:

Financial COI can bias research. Although authors seeking to publish in peer-reviewed surgery journals are required to provide COI disclosures, editorial board members’ COI disclosures are generally not disclosed to readers.

Methods:

We present a cross-sectional analysis of industry funding to editorial board members of high-impact surgery journals. We reviewed top US-based surgery journals by impact factor to determine the presence of financial COI in members of each journal's editorial board. The prevalence and magnitude of COI was determined using 2018 industry reported payments found in the Centers for Medicare and Medicaid Services Open Payments database. Journal websites were also reviewed looking for the presence of editorial board disclosure statements.

Results:

A total of 1002 names of editorial board members from the top 10 high-impact American surgery journals were identified. Of 688 individual physicians based in the USA, 452 (65.7%) were found to have received industry payments in 2018, totaling $21,916,503 with a median funding amount per physician of $1253 (interquartile range $156-$10,769). Funding levels varied by surgical specialty and journal. Editorial board disclosure information was found in only 3.3% of physicians.

Conclusions:

Industry funding to editorial board members of high impact surgery journals is prevalent and underreported. Mechanisms of disclosure for COI are needed at the editorial board level to provide readers full transparency. This would acknowledge this COI of editorial board members, and thereby attempt to potentially further reduce the risk of bias in editorial decisions.
Are General Surgery Residencies Preparing Graduates for the Practice of Today’s General Surgeon? An Analysis of American Board of Surgery Data From Applicants and Re-certifying Surgeons
Authors: Cortez Alexander R. , Ibáñez Beatriz , Winer Leah K. , Jones Andrew T. , Quillin Ralph C. , Valentine R. James , Potts John R.
Published: June 2021

Objective:

To compare the operative experience of general surgery residents and practicing general surgeons.

Summary of Background Data:

The scope of general surgery has evolved, yet it remains unknown whether residents are being exposed to the right mix of operations during residency.

Methods:

A retrospective review of operative case logs submitted to the American Board of Surgery by US general surgery graduates and practicing general surgeons from 2013 to 2017 was performed. The operative experience of both cohorts was calculated as a proportion of total experience and ranked by frequency. The proportional experience between cohorts was analyzed using factorial analysis of variance.

Results:

During the 5-year period, 5482 graduates applied for initial American Board of Surgery certification, and 4152 diplomates applied for recertification. Among all operative domains, the graduate experience was similar to that of diplomates in 6 of 12 areas (abdomen, alimentary tract, endoscopy, endocrine, other, skin/soft tissue; all P > 0.05). Residents have a greater experience in subspecialty areas (pediatric, thoracic, trauma, vascular, and plastic) at the expense of fewer breast procedures (all P < 0.05). The 30 operations most commonly performed by graduates comprised 67% of their total operative experience. Among these, residents performed 25 cases ≥10 times, 14 cases ≥20 times, and 7 cases ≥40 times.

Conclusions:

The operative experience of graduating US general surgery residents is largely similar to that of practicing general surgeons, particularly for core general surgery domains. These data offer reassurance that surgical training in the modern era appropriately exposes residents to the operations they may perform in practice.
Is Adjuvant Therapy a Better Option for Esophageal Squamous Cell Carcinoma Patients Treated With Esophagectomy? A Prognosis Prediction Model Based on Multicenter Real-World Data
Authors: Yang Wenlei , Liu Fangfang , Xu Ruiping , Yang Wei , He Yu , Liu Zhen , Zhou Fuyou , Heng Fanxiu , Hou Bolin , Zhang Lixin , Chen Lei , Zhang Fan , Cai Fen , Xu Huawen , Lin Miaoping , Liu Mengfei , Pan Yaqi , Liu Ying , Hu Zhe , Chen Huanyu , He Zhonghu , Ke Yang
Published: June 2021

Objective:

To construct a prediction model for more precise evaluation of prognosis which will allow personalized treatment recommendations for adjuvant therapy in patients following resection of ESCC.

Background:

Marked heterogeneity of patient prognosis and limited evidence regarding survival benefit of various adjuvant therapy regimens pose challenges in the clinical treatment of ESCC.

Methods:

Based on comprehensive clinical data obtained from 4129 consecutive patients with resected ESCC in a high-risk region in China, we identified predictors for overall survival through a 2-phase selection based on Cox proportional hazard regression and minimization of Akaike information criterion. The model was internally validated using bootstrapping and externally validated in 1815 patients from a non-high-risk region in China.

Results:

The final model incorporates 9 variables: age, sex, primary site, T stage, N stage, number of lymph nodes harvested, tumor size, adjuvant treatment, and hemoglobin level. A significant interaction was also observed between N stage and adjuvant treatment. N1+ stage patients were likely to benefit from addition of adjuvant therapy as opposed to surgery alone, but adjuvant therapy did not improve overall survival for N0 stage patients. The C-index of the model was 0.729 in the training cohort, 0.723 after bootstrapping, and 0.695 in the external validation cohort. This model outperformed the seventh edition American Joint Committee on Cancer staging system in prognostic prediction and risk stratification.

Conclusions:

The prediction model constructed in this study may facilitate precise prediction of survival and inform decision-making about adjuvant therapy according to N stage.
Sex Representation Among Principal Investigators in Cardiac Surgery Clinical Trials in the United States
Authors: Nguyen Quynh , Luc Jessica G. Y. , Lawton Jennifer S. , Chikwe Joanna , Cornwell Lorraine D. , Simpson Katherine , Estrera Anthony L. , Moon Marc R. , Preventza Ourania
Published: June 2021

Objective:

The aim of this study was to determine the sex representation among principal investigators (PIs) in US cardiac surgery clinical trials.

Summary Background Data:

Being a principal investigator in a US clinical trial confers national recognition among peers. Sex representation among principal investigators (PIs) in US cardiac surgery clinical trials has not been evaluated.

Methods:

We evaluated 124 US cardiac surgery trials registered on Clin-icalTrials.gov from 2014 to 2019. Sixty trials included PIs (n = 266) from 128 institutions that had a combined total of 1040 adult cardiac surgeons. We examined sex representation among junior-level (instructor or assistant professor) and senior-level (associate, full, or Emeritus professor) PIs by calculating the participation-to-prevalence ratio (PPR), whereby a PPR range of 0.8 to 1.2 reflects equitable representation.

Results:

The pool representation percentage was 6.1% (63/1040) for women and 93.9% (977/1040) for men. A total of 266 PI positions were assigned to adult cardiac surgeons: 6 (9.5%; PPR = 0.37) from the female pool and 260 (26.6%; PPR = 1.04) from the male pool (P = 0.004). The percentage of PIs with studies funded by industry was 9.5% ofthe female pool (PPR = 0.39) and 25.0% of the male pool (PPR = 1.04) (P = 0.009). No National Institutes of Health-funded or other funded trials had female PIs. An overall trend was observed toward disproportionally more men than women among PIs, especially at the senior level (P = 0.027).

Conclusions:

Equitable opportunities for PI positions are available for junior-level but not senior-level cardiothoracic surgeons. These results suggest a need for active engagement and promotion of equal opportunities in cardiac surgery.
Enhanced Recovery 2.0 – Same Day Discharge With Mobile App Follow-up After Minimally Invasive Colorectal Surgery
Authors: Lee Lawrence , Eustache Jules , Baldini Gabriele , Liberman A. Sender , Charlebois Patrick , Stein Barry , Fiore Julio F. , Feldman Liane S.
Published: June 2021

Objective:

To investigate the feasibility of SDD protocol with postdischarge follow-up using a mobile phone app in patients undergoing elective minimally-invasive colectomy.

Summary of Background Data:

Discharge before gastrointestinal recovery and use of mobile health technology for remote follow-up may allow for SDD after minimally-invasive colectomy within an ERP.

Methods:

Adult patients undergoing elective laparoscopic colectomy or loop ileostomy reversal from February 2020 to November 2020 were screened for eligibility. Patients were eligible if they lived within a 30-minute drive from the hospital, had an adequate support system at home, and owned a smart phone. Patients were discharged from the recovery room on the day of surgery based on set criteria with postdischarge remote follow-up using a mobile application. Feasibility was defined as discharge on the day of surgery without emergency department (ED) visit or readmission within the first 3 days. 30-day complications, ED visits, and readmissions were compared to a non-SDD historical cohort (May 2019–March 2020) also remotely followed-up using the same mobile phone app (standard ERP group).

Results:

A total of 48 patients were recruited to SDD, of which 77% were discharged on the day of surgery without subsequent ED visit in the first 72 hours. There were 11 patients that could not be discharged, including 7 for failure of discharge criteria and 4 for intraoperative complications/concerns. Overall 30-day complications in the SDD group (17%) was similar to the standard ERP group (15%, P = 0.813). ED visits (SDD10% vs standard ERP8%, P = 0.664) and readmissions (6% vs 4%, P = 0.681) were also similar.

Conclusions and Relevance:

Findings from this study support the feasibility of a SDD protocol in select patients undergoing minimally-invasive colorectal resection. SDD colectomy protocols may represent the next evolution of ERP and postoperative recovery.
Totally Laparoscopic Transhiatal Middle and Lower Mediastinal Lymphadenectomy for Esophageal Cancer
Authors: Hoshino Akihiro , Tokunaga Masanori , Kinugasa Yusuke
Published: June 2021

Laparoscopic transhiatal approach to esophagectomy with mediastinal lymphadenectomy usually involves hand-assisted laparoscopic surgery. However, a totally laparoscopic approach can decrease the size of the abdominal wound and curtail the impact on respiration. We present a novel, totally laparoscopic transhiatal technique that may reduce respiratory complications following thoracoscopic esophagectomy. We performed a series of combined, thoracoscopic and laparoscopic, McKeown esophagectomies via a neck-abdominal first approach. Middle and lower mediastinal lymphadenectomy, subtracheal lymph node removal, and esophageal mobilization were performed via a totally laparoscopic transhiatal approach. Subsequently, upper mediastinal lymph nodes were dissected using a thoracoscopic approach. Finally, an esophagogastric anastomosis was constructed in the neck. For the 36 patients in this series, the median values of the total operative duration and the thoracoscopic portion were 499 minutes (range, 315 to 678 min) and 106 minutes (range, 67 to 243 min), respectively. Postoperative pneumonia occurred in 3 (8.3%) patients. Totally laparoscopic transhiatal approach is feasible for esophageal surgery with acceptable short-term outcomes.
Site level factors that affect the rate of adaptive evolution in humans and chimpanzees; the effect of contracting population size
Authors: Soni Vivak , Moutinho Ana Filipa , Eyre-Walker Adam
Published: June 2021

It has previously been shown in other species that the rate of adaptive evolution is higher at sites that are more exposed in a protein structure and lower between amino acid pairs that are more dissimilar. We have investigated whether these patterns are found in the divergence between humans and chimpanzees using an extension of the MacDonald-Kreitman test. We confirm previous findings and find that the rate of adaptive evolution, relative to the rate of mutation, is higher for more exposed amino acids, lower for amino acid pairs that are more dissimilar in terms of their polarity, volume and lower for amino acid pairs that are subject to stronger purifying selection, as measured by the ratio of the numbers of non-synonymous to synonymous polymorphisms (pN /pS). However, the slope of this latter relationship is significantly shallower than in Drosophila species. We suggest that this is due to the population contraction that has occurred since humans and chimpanzees diverged. We demonstrate theoretically that population size reduction can generate an artefactual positive correlation between the rate of adaptive evolution and any factor that is correlated to the mean strength of selection acting against deleterious mutations, even if there has been no adaptive evolution (the converse is also expected). Our measure of selective constraint, pN /pS, is negatively correlated to the mean strength of selection, and hence we would expect the correlation between the rate of adaptive evolution to also be negatively correlated to pN /pS, if there is no adaptive evolution. The fact that our rate of adaptive evolution is positively correlated to pN /pS suggests that the correlation does genuinely exist, but that is has been attenuated by population size contraction.
Classification of Fetal State through the application of Machine Learning techniques on Cardiotocography records: Towards Real World Application
Authors: Ventura Dadario Andrew Maranhão , Espinoza Christian , Araújo Nogueira Wellington
Published: June 2021

Objective

Anticipating fetal risk is a major factor in reducing child and maternal mortality and suffering. In this context cardiotocography (CTG) is a low cost, well established procedure that has been around for decades, despite lacking consensus regarding its impact on outcomes.

Machine learning emerged as an option for automatic classification of CTG records, as previous studies showed expert level results, but often came at the price of reduced generalization potential.

With that in mind, the present study sought to improve statistical rigor of evaluation towards real world application.

Materials and Methods

In this study, a dataset of 2126 CTG recordings labeled as normal, suspect or pathological by the consensus of three expert obstetricians was used to create a baseline random forest model.

This was followed by creating a lightgbm model tuned using gaussian process regression and post processed using cross validation ensembling.

Performance was assessed using the area under the precision-recall curve (AUPRC) metric over 100 experiment executions, each using a testing set comprised of 30% of data stratified by the class label.

Results

The best model was a cross validation ensemble of lightgbm models that yielded 95.82% AUPRC.

Conclusions

The model is shown to produce consistent expert level performance at a less than negligible cost. At an estimated 0.78 USD per million predictions the model can generate value in settings with CTG qualified personnel and all the more in their absence.
Inferring SARS-CoV-2 RNA shedding into wastewater relative to time of infection
Authors: Cavany Sean , Bivins Aaron , Wu Zhenyu , North Devin , Bibby Kyle , Perkins T. Alex
Published: June 2021

Since the start of the COVID-19 pandemic, there has been interest in using wastewater monitoring as an approach for disease surveillance. A significant uncertainty that would improve interpretation of wastewater monitoring data is the intensity and timing with which individuals shed RNA from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into wastewater. By combining wastewater and case surveillance data sets from a university campus during a period of heightened surveillance, we inferred that individual shedding of RNA into wastewater peaks on average six days (50% uncertainty interval (UI): 6 – 7; 95% UI: 4 – 8) following infection, and that wastewater measurements are highly overdispersed (negative binomial dispersion parameter,k= 0.39 (95% credible interval: 0.32 – 0.48)). This limits the utility of wastewater surveillance as a leading indicator of secular trends in SARS-CoV-2 transmission during an epidemic, and implies that it could be most useful as an early warning of rising transmission in areas where transmission is low or clinical testing is delayed or of limited capacity.
Transmission of SARS-CoV-2 associated with aircraft travel: a systematic review (Version 1)
Authors: Rosca EC , Heneghan C , Spencer EA , Brassey J , Plüddemann A , Onakpoya IJ , Evans D , Conly JM , Jefferson T
Published: June 2021

Background

Air travel may be associated with the spread of viruses via infected passengers and potentially through in-flight transmission. Given the novelty of the SARS-CoV-2 virus, transmission associated with air travel is based on what is known about the dynamics of transmission of other respiratory virus infections, especially those due to other coronaviruses and influenza. Our objective was to provide a rapid summary and evaluation of relevant data on the transmission of SARS-CoV-2 aboard aircraft, report important policy implications, and highlight research gaps requiring urgent attention.

Methods

This review is part of an Open Evidence Review on Transmission Dynamics of SARS-CoV-2. We searched LitCovid, medRxiv, Google Scholar, and the WHO Covid-19 database from 1 February 2020 to 27 January 2021 and included studies on the transmission of SARS-CoV-2 aboard aircraft. We assessed study quality based on five criteria and reported important findings.

Results

We included 18 studies on in-flight transmission of SARS-CoV-2, representing 130 unique flights and two studies on wastewater from aircraft. The overall quality of reporting was low. Two wastewater studies reported PCR-positive SARS-CoV-2 samples, but with relatively high Cycle threshold values ranging from 36 to 40. The definition of an index case was very heterogeneous across the studies. The proportion of contacts traced ranged from 0.68% to 100%. In total, the authors successfully traced 2800/19729 passengers, 140/180 crew members, and 8/8 medical staff. Altogether, 273 index cases were reported, with 64 secondary cases. No secondary cases were reported in three studies, each investigating one flight. The secondary attack rate among the studies that followed up >80% of the passengers and crew (including data on 10 flights) varied between 0% and 8.2%. The included studies reported on the possibility of SARS-CoV-2 transmission from asymptomatic, pre-symptomatic, and symptomatic individuals. Viral cultures were performed in two studies, with 10 positive results reported. Genomic sequencing and phylogenetic analysis were performed in individuals from four flights, with the completeness of genomic similarity ranging from 81-100%.

Conclusion

Current evidence suggests that SARS-CoV-2 can be transmitted during aircraft travel, but the published data do not permit any conclusive assessment of the likelihood and extent. Furthermore, the quality of evidence from most published studies is low. The variation in study design and methodology restricts the comparison of findings across studies. Standardized guidelines for conducting and reporting future studies of transmission on aircrafts should be developed.
Virtual care and the impact of COVID-19 on nursing: A single centre evaluation
Authors: Hughes Luke , Petrella Anika , Phillips Natasha , Taylor Rachel M
Published: June 2021

Aims

The overall aim of this evaluation was to look at the impact of the changes in working practices during the pandemic on nurses. This secondary analysis provided an evaluation of virtual care and being able/required to work from home.

Design

This was secondary analysis of an evaluation using semi-structured interviews.

Methods

Conducted at a single National Health Service (NHS) university hospital in the United Kingdom between May-July 2020. Forty-eight operational leads and nurses participated in semi-structured interviews which were digitally recorded, transcribed verbatim and analysed using a framework analysis.

Results

Two overarching themes emerged relating to the patient experience and nursing experience. There were both positive and negative elements associated with virtual care and remote working related to these themes. However, the majority of nurses found virtual clinics were useful when proper resources were provided, and managerial strategies were put in place to support them. Participants felt virtual care could benefit many but not all patient groups moving forward, and that flexibility around working from home would be desirable in the future.

Conclusion

Virtual care and remote working were implemented to accommodate the restrictions imposed because of the pandemic. The benefits of these changes to nurses and patients support these being business as usual. However, clear policies are needed to ensure nurses feel supported when working remotely and there are robust assessments in place to ensure virtual care is provided to patients who have access to the necessary technology.

Impact

This was a study of the move to virtual care and remote working during the COVID-19 pandemic. Telemedicine and flexible working were not common in the NHS prior to the pandemic but the current evaluation supports the role out of these as standard care with policies in place to ensure nurses and patients are appropriately supported.
Normal mean oral temperature is 98°F, not 98.2°F or 98.6°F
Authors: Kumar Nitin , Ronanki Kavya , Panda Prasan Kumar , Kapoor Mayank , Singh Yogesh , Bhadoriya Ajeet Singh
Published: June 2021

Background

98.6°F is generally accepted as normal body temperature as defined by Wunderlich (1868) and later challenged by Mackowiak (1992) and Protsiv (2020) who concluded as 98.2°F based on cross-sectional studies. Hence, the normal body temperature at present needs quantification?

Methods

A longitudinal study on the healthy population of Northen-India were followed-up over 1-year. Participants were advised for self-monitoring of oral temperature with a standard digital thermometer in either left or right sublingual pocket and record it in the thermometry diary. The study was considered complete if the participant had all the three phases of the study (i.e. non-febrile, febrile, and post-febrile phases) or completed the duration of the study.

Results

The mean oral temperature of the participants (n=144) during the non-febrile and post-febrile phases (temperature readings=6543) were 98°F (SD, 0.61) and 98.01°F (SD, 0.60) respectively (P<0.001). The mean oral temperature during post-febrile phase was found to be 0.01°F higher than non-febrile phase. With the diurnal variability, the morning (AM), noon (AN), and afternoon (PM) mean temperatures were 97.91, 98.08, and 98.27°F (P<0.001) respectively during the non-febrile phase. Similar trends were observed in variability among men and women, and seasons.

Conclusions

The mean oral temperature is 98°F (SD, 0.61). The temperature is as low as 96.90F and as high as 99.10F. The temperature during post-febrile phase was found to be higher than the non-febrile phase temperature like PM over AN & AM, women over men, summer over other seasons in the non-febrile phase, spring over others in the post-febrile phase.
A landscape of synergistic drug combinations in non-small-cell lung cancer
Authors: Nair Nishanth Ulhas , Greninger Patricia , Friedman Adam , Amzallag Arnaud , Cortez Eliane , Sahu Avinash Das , Lee Joo Sang , Dastur Anahita , Egan Regina K. , Murchie Ellen , Crowther Giovanna Stein , McClanaghan Joseph , Boisvert Jessica , Damon Leah , Ho Jeffrey , Tam Angela , Garnett Mathew J , Engelman Jeffrey A. , Haber Daniel A. , Ruppin Eytan , Benes Cyril H.
Published: June 2021

Targeted therapeutics have advanced cancer treatment, but single agent activity remains limited by de novo and acquired resistance. Combining targeted drugs is broadly seen as a way to improve treatment outcome, motivating the ongoing search for efficacious combinations. To identify synergistic targeted therapy combinations and study the impact of tumor heterogeneity on combination outcome, we systematically tested over 5,000 two drug combinations at multiple doses across a collection of 81 non-small cancer cell lines. Both known and novel synergistic combinations were identified. Strikingly, very few combinations yield synergy across the majority of cell line models. Importantly, synergism mainly arises due to sensitization of single agent resistant models, rather than further sensitize already sensitive cell lines, frequently via dual targeting of a single or two highly interconnected pathways. This drug combinations resource, the largest of its kind should help delineate new synergistic regimens by facilitating the understanding of drug synergism in cancer.
HLA Allele Imputation with Multitask Deep Convolutional Neural Network
Authors: Chi Calvin
Published: June 2021

Motivation

The Human leukgocyte antigen (HLA) system is a highly polymorphic gene complex encoding the major histocompatibility complex proteins in humans. HLA alleles are of strong epidemiological interest for their large effect sizes in associations with autoimmune diseases, infectious diseases, severe drug reactions, and transplant medicine. Since HLA genotyping can be time-consuming and cost-prohibitive, methods to impute HLA alleles from SNP genotype data have been developed, including HLA Genotype Imputation with Attribute Bagging (HIBAG), HLA*IMP:02, and SNP2HLA. However, limitations of these imputation programs include imputation accuracy, computational runtime, and ability to impute HLA allele haplotypes.

Results

We present a deep learning framework for HLA allele imputation using a multitask convolutional neural network (CNN) architecture. In this approach, we use phased SNP genotype data flanking ±250 kb from each HLA locus to simultaneously impute HLA allele haplotyes across loci HLA-A, -B, -C, -DQA1, -DQB1, -DPA1, -DPB1, and -DRB1. We start by tokenizing phased genotype sequences into k-mers that serve as input to the model. The CNN architecture starts with a shared embedding layer for learning low-dimensional representations of k-mers, shared convolutional layers for detecting genotype motifs, and branches off into separate densely-connected layers for imputing each HLA loci. We present evidence that the CNN used information from known tag SNPs to impute HLA alleles, and demonstrate the architecture is robust against a selection of hyperparameters. On the T1DGC dataset, our model achieved 97.6% imputation accuracy, which was superior to SNP2HLA’s performance and comparable to HIBAG’s performance. However, unlike HIBAG, our method can impute an entire HLA haplotype sequence instead of imputing one locus at a time. Additionally, by separating the training and inference steps, our imputation program provides user flexibility to reduce usage time.

Availability

The source code is available at https://github.com/CalvinTChi/HLA_imputation

Contact

calvin.chi@berkeley.edu
Development of a multiplex real-time PCR assay for BCG and validation in a clinical laboratory
Authors: Duffy Shannon C , Venkatesan Manigandan , Chothe Shubhada , Poojary Indira , Verghese Valsan Philip , Kapur Vivek , Behr Marcel A , Michael Joy S
Published: June 2021

Mycobacterium bovisbacille Calmette-Guérin (BCG) is a live attenuated vaccine which can result in local or disseminated infection, most commonly in immunocompromised individuals. Differentiation of BCG from other members of theMycobacterium tuberculosiscomplex (MTBC) is required to diagnose BCG disease, which requires specific management. Current methods for BCG diagnosis are based on mycobacterial culture and conventional PCR; the former is time-consuming and the latter often unavailable. Further, there are reports that certain BCG strains may be associated with a higher rate of adverse events. This study describes the development of a two-step multiplex real-time PCR assay which uses single nucleotide polymorphisms to detect BCG and identify early or late BCG strains. The assay has a limit of detection of 1 pg BCG boiled lysate DNA and was shown to detect BCG in both pure cultures and experimentally infected tissue. Performance was assessed on 19 suspected BCG clinical isolates at Christian Medical College in Vellore, India taken from January 2018 to August 2020. Of these 19 isolates, 10 were identified as BCG (6 early and 4 late strains) and 9 were identified as other MTBC members. Taken together, the results demonstrate the ability of this assay to identify and characterize BCG disease from cultures and infected tissue. The capacity to identify BCG may improve patient management and the ability to discriminate between BCG strains may enable BCG vaccine pharmacovigilance.
Direct comparison of venipuncture serum draws versus whole blood finger-stick specimens by anti-COVID-19 IgG/IgM rapid lateral flow immunoassay and ELISA
Authors: Baig Irfan , Tagwerker Christian , Brunson Eric J. , Mundo Kristine , Dutra-Smith Davan , Carias-Marines Mary Jane , de Zoysa Ranulu Samanthi , Smith David J.
Published: June 2021

During the COVID-19 pandemic, manufacturers have developed several diagnostic test kits that include lateral flow immunoassays (LFIA) also known as rapid cassette testing. Rapid cassette testing provides qualitative test results indicating the presence or absence of IgG and IgM antibodies to determine COVID-19 (SARS-CoV-2) infection among individuals. Venipuncture blood draws have been the traditional and widely proposed sample collection method but is costly and not applicable to point-of-care testing (POC) and in remote settings. Whole blood finger-stick blood collections traditionally used by diabetics for glucose level testing is an ideal scenario, but raises concerns regarding the outcome of test results in regards to specificity and sensitivity. In this study we directly compare simultaneous collections of venipuncture serum (SST) blood draws and whole blood finger-sticks (n = 75) to detect human Anti-COVID-19 IgG and IgM antibodies using an EUA-approved lateral flow immunoassay, showing equal to enhanced performance characteristics for this specimen type.
The Prevention and Control of Cancer by Metformin in Patients with Type 2 Diabetes: A Systematic Mapping Review
Authors: Mitchell Albania , Price Michelle , Cipriano Gabriela
Published: June 2021

Objective

Metformin is commonly used as a first line therapy for type 2 diabetes; however, existing evidence suggests an influence in oncology. The objective of this systematic mapping review was to describe current literature regarding metformin and its role in preventing and /or controlling cancer in patients with type 2 diabetes.

Method

We searched PubMed, Cochrane Library, and ClinicalTrials.gov in February 2018 and April 2019 to identify research studies, systematic reviews and meta-analyses. Of the 318 citations identified, 156 publications were included in this analysis.

Results

The most common cancer types researched were colorectal, liver, prostate, lung and breast with the United States contributing the most to this data. Author teams averaged six members and most studies were funded. Only 68% of the articles were available open access. Ovarian and esophageal cancers were amongst the least studied, but the most costly for care.
P2X4 Purinergic Receptors as a Therapeutic Target in Aggressive Prostate Cancer
Authors: Maynard Janielle P. , Lu Jiayun , Vidal Igor , Hicks Jessica , Mummert Luke , Ali Tamirat , Kempski Ryan , Carter Ayanna M. , Sosa Rebecca , Peiffer Lauren B. , Joshu Corinne E. , Lotan Tamara L. , De Marzo Angelo M. , Sfanos Karen S.
Published: June 2021

Prostate cancer (PCa) remains a leading cause of cancer-related deaths in American men and treatment options for metastatic PCa are limited. There is a critical need to identify new mechanisms that contribute to PCa progression, that distinguish benign from lethal disease, and that have potential for therapeutic targeting. P2X4 belongs to the P2 purinergic receptor family that is commonly upregulated in cancer and is associated with poorer outcomes. Herein, we report that the P2X4 purinergic receptor is overexpressed in PCa, associated with PCa metastasis, and a driver of tumor development in vivo. We observed P2X4 protein expression primarily in epithelial cells of the prostate, a subset of CD66+ neutrophils, and most CD68+ macrophages. Our analysis of tissue microarrays representing 491 PCa cases demonstrated significantly elevated P2X4 expression in cancer compared to benign tissue spots, in prostatic intraepithelial neoplasia, in cancer from White compared to Black men, and in PCa with ERG positivity or with PTEN loss. High P2X4 expression in benign tissues was likewise associated with the development of metastasis after radical prostatectomy. Treatment with P2X4-specific agonist CTP increased transwell migration and invasion of PC3, DU145, and CWR22Rv1 PCa cells. P2X4 antagonist 5-BDBD treatment resulted in a dose-dependent decrease in viability of PC3, DU145, LNCaP, CWR22Rv1, TRAMP-C2, Myc-CaP, BMPC1, and BMPC2 cells and decreased DU145 cell migration and invasion. Knockdown of P2X4 attenuated growth, migration, and invasion of PCa cells. Finally, knockdown of P2X4 in Myc-CaP cells resulted in significantly attenuated subcutaneous allograft growth in FVB/NJ mice. Collectively, these data strongly support a role for the P2X4 purinergic receptor in PCa aggressiveness and identifies P2X4 as a candidate for therapeutic targeting.
Computer-Assisted Mitotic Count Using a Deep Learning-based Algorithm Improves Inter-Observer Reproducibility and Accuracy in canine cutaneous mast cell tumors
Authors: Bertram Christof A. , Aubreville Marc , Donovan Taryn A. , Bartel Alexander , Wilm Frauke , Marzahl Christian , Assenmacher Charles-Antoine , Becker Kathrin , Bennett Mark , Corner Sarah , Cossic Brieuc , Denk Daniela , Dettwiler Martina , Gonzalez Beatriz Garcia , Gurtner Corinne , Haverkamp Ann-Kathrin , Heier Annabelle , Lehmbecker Annika , Merz Sophie , Noland Erica L. , Plog Stephanie , Schmidt Anja , Sebastian Franziska , Sledge Dodd G. , Smedley Rebecca C. , Tecilla Marco , Thaiwong Tuddow , Fuchs-Baumgartinger Andrea , Meuten Don J. , Breininger Katharina , Kiupel Matti , Maier Andreas , Klopfleisch Robert
Published: June 2021

The mitotic count (MC) is an important histological parameter for prognostication of malignant neoplasms. However, it has inter- and intra-observer discrepancies due to difficulties in selecting the region of interest (MC-ROI) and in identifying/classifying mitotic figures (MFs). Recent progress in the field of artificial intelligence has allowed the development of high-performance algorithms that may improve standardization of the MC. As algorithmic predictions are not flawless, the computer-assisted review by pathologists may ensure reliability. In the present study we have compared partial (MC-ROI preselection) and full (additional visualization of MF candidate proposal and display of algorithmic confidence values) computer-assisted MC analysis to the routine (unaided) MC analysis by 23 pathologists for whole slide images of 50 canine cutaneous mast cell tumors (ccMCTs). Algorithmic predictions aimed to assist pathologists in detecting mitotic hotspot locations, reducing omission of MF and improving classification against imposters. The inter-observer consistency for the MC significantly increased with computer assistance (interobserver correlation coefficient, ICC = 0.92) compared to the unaided approach (ICC = 0.70). Classification into prognostic stratifications had a higher accuracy with computer assistance. The algorithmically preselected MC-ROIs had a consistently higher MCs than the manually selected MC-ROIs. Compared to a ground truth (developed with immunohistochemistry for phosphohistone H3), pathologist performance in detecting individual MF was augmented when using computer assistance (F1-score of 0.68 increased to 0.79) with a reduction in false negatives by 38%. The results of this study prove that computer assistance may lead to a more reproducible and accurate MCs in ccMCTs.
Assessing genome-wide dynamic changes in enhancer activity during early mESC differentiation by FAIRE-STARR-seq
Authors: Glaser Laura V. , Steiger Mara , Fuchs Alisa , van Bömmel Alena , Einfeldt Edda , Chung Ho-Ryun , Vingron Martin , Meijsing Sebastiaan H.
Published: June 2021

Embryonic stem cells (ESCs) can differentiate into any given cell type and therefore represent a versatile model to study the link between gene regulation and differentiation. To quantitatively assess the dynamics of enhancer activity during the early stages of murine ESC differentiation, we analyzed accessible genomic regions using STARR-seq, a massively parallel reporter assay. This resulted in a genome-wide quantitative map of active mESC enhancers, in pluripotency and during the early stages of differentiation. We find that only a minority of accessible regions is active and that such regions are enriched near promoters, characterized by specific chromatin marks, enriched for distinct sequence motifs, and modeling shows that active regions can be predicted from sequence alone. Regions that change their activity upon retinoic acid-induced differentiation are more prevalent at distal intergenic regions when compared to constitutively active enhancers. Further, analysis of differentially active enhancers verified the contribution of individual TF motifs toward activity and inducibility as well as their role in regulating endogenous genes. Notably, the activity of retinoic acid receptor alpha (RARα) occupied regions can either increase or decrease upon the addition of its ligand, retinoic acid, with the direction of the change correlating with spacing and orientation of the RARα consensus motif and the co-occurrence of additional sequence motifs. Together, our genome-wide enhancer activity map elucidates features associated with enhancer activity levels, identifies regulatory regions disregarded by computational prediction tools, and provides a resource for future studies into regulatory elements in mESCs.