bluuebunny/crossref_metadata_2025 huggingface dataset:
A Diagnostic Nomogram for Predicting the Risk of Anastomotic Leakage in Elderly Patients With Rectal Cancer: A Single-center Retrospective Cohort Study
Authors: Liu Dongliang , Zhou Hong , Liu Liu , Zhu Zhiqiang , Liu Shaojun , Fang Yu
Published: July 2021

Background:

Laparoscopic resection for rectal cancer has been gaining popularity over the past 2 decades. Whether elderly patients had more benefits from laparoscopy-assisted anterior resection (LAR) need further investigation when comparing with open anterior resection (OAR).

Objectives:

This study aimed to evaluate the clinical outcomes and prognosis of LAR in elderly patients (65 y and above) with rectal cancer and investigate the factors associated with the anastomotic leakage (AL). Besides, the study sought to create a nomogram for precise prediction of AL after anterior resection for rectal cancer.

Materials and Methods:

A total of 343 rectal cancer patients over 65 years old who underwent LAR or OAR at a single center between January 2013 to January 2021 were retrospectively reviewed. Univariate analysis was conducted to explore potential risk factors for AL, and a nomogram for AL was created based on the multivariate logistic regression model.

Results:

A total of 343 patients were included in this study, 271 patients in LAR group and 72 patients in OAR group. Most of the variables were comparable between the 2 groups. The mean operative time was longer in the LAR group than that in the OAR group (191.66±58.33 vs. 156.85±53.88 min, P<0.0001). The LAR group exhibited a significantly lower intraoperative blood loss than the OAR group (85.17±50.03 vs. 131.67±79.10 mL; P<0.0001). Moreover, laparoscopic surgery resulted in shorter postoperative hospital stay, lower rates of diverting stoma and receiving sphincter sparing surgery in comparison with open surgery. The overall rates of complications were 25.1% and 40.3% in the LAR and OAR groups (P=0.011), respectively. And the reoperation rates in the OAR group (0%) was lower than in the LAR group (1.5%), but the difference did not reach statistical significance (P=0.300). Sex, location of tumor, diverting stoma and combined organ resection were identified as independent risk factors for AL based on multivariate analysis. Such factors were selected to develop a nomogram. After a median follow-up of 37.0 months, our study showed no significant difference in overall survival or disease free survival between the 2 groups for treatment of rectal cancer.

Conclusions:

This study suggests that LAR is an alternative minimally invasive surgical procedure in patients above 65 years with better short-term outcomes and acceptable long-term outcomes compared with OAR. In addition, our nomogram has satisfactory accuracy and clinical utility may benefit for clinical decision-making.
The Diagnostic Value of Coagulation Indicators and Inflammatory Markers in Distinguishing Between Strangulated and Simple Intestinal Obstruction
Authors: Li Haijun , Sun Dian , Sun Duocheng , Xiao Zhong , Zhuang Jiongyu , Yuan Chunlei
Published: July 2021

Background:

Intestinal obstruction with strangulation can be life-threating, and it is critical to make an accurate and timely diagnosis for emergency surgery.

Objective:

This was aimed to investigate the value of coagulation indicators and inflammatory markers in distinguishing between strangulated and simple intestinal obstruction.

Materials and Methods:

Fifty-four patients with intestinal obstruction were retrospectively studied. The correlation between coagulation indicators and inflammatory markers with intestinal obstruction was analyzed. Receiver operating characteristic curves were created to assess their ability in discriminative diagnosis.

Results:

Levels of fibrinogen (Fib), C-reactive protein (CRP), neutrophil ratio, and D-Dimer were significantly greater, while thrombin time was significantly shorter in strangulated intestinal obstruction compared with simple intestinal obstruction. Furthermore, Fib levels in the necrosis subgroup of strangulated intestinal obstruction were significantly higher than those in the ischemia subgroup and simple intestinal obstruction group. The areas under the receiver operating characteristic curve were 0.58 for white blood cells, 0.78 for CRP, and 0.80 for Fib. Using the optimal cutoff values of Fib (3.71 g/L) and CRP (14.54 mg/L), the sensitivity, specificity, positive predictive value, and negative predictive value in discriminating between strangulated intestinal obstruction and simple intestinal obstruction were 51.43%, 100%, 100%, and 52.78% for Fib, and 56.25%, 94.44%, 94.74%, and 54.84% for CRP, respectively.

Conclusions:

Fib and CRP demonstrate good performance in predicting strangulation and are indicative of intestinal necrosis and ischemia. The combination of this coagulation indicator and inflammatory marker holds potential for better discrimination between strangulated and simple intestinal obstruction.
Serious health-related suffering and palliative care in South Asian countries
Authors: Nambiar Ashwin R. , Rana Smriti , Rajagopal M.R.
Published: July 2021

Purpose of review

South Asia, with a population of 1.79 billion, has close to 9.9 million individuals experiencing serious health-related suffering (SHS). South Asia accounts for 10.23% of the world's cancer incidence. The prevalence of cancer mortality in the region is 68.44%, significantly higher than the world average of 59.74%. This poor outcome highlights the need to focus on SHS in the region. This review was undertaken to assess the current status of palliative care inequities in the region and to guide future action.

Recent findings

Using morphine-equivalent doses of opioid analgesics (excluding methadone) per cancer death as a proxy measure for access to palliative care, the International Narcotics Control Board data in 2020 show poor access to palliative care. Less than 4% of those in need are able to access palliative care in India, whereas in Afghanistan only 0.2% have access. Inappropriate end-of-life care (EOLC) and catastrophic out-of-pocket health expenditure compound the problem.

The solutions involve the introduction of national programs for palliative care, demonstration of culturally appropriate best practices as proof of concept, favourable legislation for medical opioid access, community participation, engagement of civil society to improve awareness, inclusion of palliative and adding EOLC to medical education and need-based research.

Video abstract

http://links.lww.com/COSPC/A30.
A fatal combination of disseminated strongyloidiasis with two bacterial infections in an immunocompromised host
Authors: Vini Vineeta , Antony Sherly , Jacob Teena , Sasimohan Archana , Jacob Aneeta Mary , Idikula Mercy John , Cherian Jacob
Published: July 2021

Introduction.
Strongyloides stercoralis is an intestinal nematode that is endemic in tropical countries. It can have a variable presentation ranging from asymptomatic eosinophilia in immunocompetent hosts to disseminated disease with sepsis in immunocompromised hosts.

Case report. We report a case of chronic diarrhoea and decreased appetite in a 53-year-old man. He was a chronic alcoholic with diabetes, hypertension and dyslipidaemia and had earlier been treated for pulmonary tuberculosis. He was treated symptomatically for loose stools at a primary health care facility without relief. Following referral to our tertiary care centre, microscopic examination of the stool showed numerous larvae and a few eggs of Strongyloides stercoralis. Additionally,

Aeromonas sobria

was isolated from stool culture. The patient was discharged following improvement with a combination therapy of ivermectin, albendazole and ciprofloxacin. However, within 3 days, he was readmitted and succumbed to

Escherichia coli

sepsis.

Conclusion. Strongyloidiasis can be diagnosed easily using a very simple but often neglected investigation, namely stool microscopy. This provides an early diagnosis, based on which prompt treatment with the appropriate antihelminthics can be started, thereby reducing the probability of disseminated infection. Disseminated strongyloidiasis is a medical emergency with a poor prognosis, especially in an immunocompromised state. Such patients should be treated aggressively with antihelminthics. They must be monitored for sufficient duration in the hospital for early signs of complication. Their discharge from hospital should be planned based on a negative stool microscopy report in addition to clinical improvement, so as to decrease the mortality reported for both untreated and treated individuals.
Algoriphagus pacificus sp. nov. and Algoriphagus oliviformis sp. nov., isolated from a mariculture fishpond
Authors: Lu Huibin , Cai Zhipeng , Deng Tongchu , Qian Youfeng , Xu Meiying
Published: July 2021

Two Gram-stain-negative, catalase-positive, oxidase-negative, rod-shaped, non-flagellated, non-spore-forming and non-motile strains (YJ13CT and H41T) were isolated from a mariculture fishpond in PR China. Comparisons based on 16S rRNA gene sequences indicated that YJ13CT and H41T shared 16S rRNA gene sequences similarities between 92.6 and 99.2 % with species of the genus

Algoriphagus

. YJ13CT only shared 93.8 % 16S rRNA gene sequence similarity with H41T. The reconstructed phylogenetic and phylogenomic trees indicated that YJ13CT and H41T clustered closely with species of the genus

Algoriphagus

. The calculated pairwise orthologous average nucleotide identity with usearch (OrthoANIu) values between strains YJ13CT and H41T and other related strains were all less than 79.5 %. The OrthoANIu value between YJ13CT and H41T was only 69.9 %. MK-7 was the predominant respiratory quinone of YJ13CT and H41T and their major cellular fatty acids contained iso-C15 : 0, C16 : 1 ω7c and C17 : 1 ω9c. The polar lipids profiles of YJ13CT and H41T consisted of phosphatidylethanolamine and several kinds of unidentified lipids. Combining the above descriptions, strains YJ13CT and H41T represent two distinct novel species of the genus

Algoriphagus

, for which the names Algoriphagus pacificus sp. nov. (type strain YJ13CT=GDMCC 1.2178T=KCTC 82450T) and Algoriphagus oliviformis sp. nov. (type strain H41T=GDMCC 1.2179T=KCTC 82451T) are proposed.
PacBio sequencing revealed variation in the microbiota diversity, species richness and composition between milk collected from healthy and mastitis cows
Authors: Ma Teng , Shen Lingling , Wen Qiannan , Lv Ruirui , Hou Qiangchuan , Kwok Lai Yu , Sun Zhihong , Zhang Heping
Published: July 2021

Mastitis is the economically most important disease of dairy cows. This study used PacBio single-molecule real-time sequencing technology to sequence the full-length 16S rRNAs from 27 milk samples (18 from mastitis and nine from healthy cows; the cows were at different stages of lactation). We observed that healthy or late stage milk microbiota had significantly higher microbial diversity and richness. The community composition of the microbiota of different groups also varied greatly. The healthy cow milk microbiota was predominantly comprised of

Lactococcus lactis

,

Acinetobacter johnsonii

, and

Bacteroides dorei

, while the milk from mastitis cows was predominantly comprised of

Bacillus cereus

. The prevalence of

L. lactis

and

B. cereus

in the milk samples was confirmed by digital droplets PCR. Differences in the milk microbiota diversity and composition could suggest an important role for some these microbes in protecting the host from mastitis while others associated with mastitis. The results of our research serve as useful references for designing strategies to prevent and treat mastitis.
Association of Sociodemographics with Out-of-Pocket Expenditure and Underinsurance in Skin Cancer Survivors
Authors: Karim Mohammad A. , Ohsfeldt Robert L. , Khodakarami Nima , Kum Hye-Chung
Published: July 2021

Background

The sociodemographic predictors of either out-of-pocket expenditure (OOP) or underinsurance among skin cancer survivors is not well reported in the literature. In this study we estimated all-cause healthcare related OOP expenditure and probability of underinsurance among insured skin cancer survivors and identified the sociodemographic predictors of these measures.

Data and Method

We pooled Medical Expenditure Panel Survey (MEPS) data from 2011 to 2015 and identified skin cancer using Clinical Classifications Software (CCS) code. Only adult (≥18 years) skin cancer survivors with full year insurance coverage were included in our study (n = 1825). We used a generalized linear model (GLM) with log link and gamma distribution to estimate OOP and a logit model to estimate the probability of underinsurance. We estimated the Average Marginal Effect (AME) to quantify the variations and their statistical significance between reference level and other levels of each predictor. Our analyses accounted for the complex survey design of MEPS.

Results

The average all-cause OOP was $1766 per person per year for a skin cancer survivor. Among all skin cancer survivors, females, those aged 60-64 years, with some college education or a degree, with income ≥400% of federal poverty level (FPL) and with non-managed-care private insurance incurred significantly higher OOP expenditure compared to their respective counterparts. In terms of underinsurance, females and those aged 60-64 years had higher probability, whereas, survivors with non-white race/ethnicity and income 200% of FPL or higher had lower probability of being underinsured compared to their respective counterparts.

Conclusion

Our study demonstrates that OOP expenditure and underinsurance varies significantly by sociodemographic factors among skin cancer survivors.
COVID-19 mortality across selected states in India: the role of age structure
Authors: Azarudeen Mohamed Jainul , Aroskar Khyati , Kurup Karishma Krishna , Dikid Tanzin , Chauhan Himanshu , Jain S.K. , Singh S.K.
Published: July 2021

Background

Mortality rates provide an opportunity to identify and act on the health system intervention for preventing deaths. Hence, it is essential to appreciate the influence of age structure while reporting mortality for a better summary of the magnitude of the epidemic.

Objectives

We described and compared the pattern of COVID-19 mortality standardized by age between selected states and India from January to November 2020.

Methods

We initially estimated the Indian population for 2020 using the decadal growth rate from the previous census (2011). This was followed by estimations of crude and age-adjusted mortality rate per million for India and the selected states. We used this information to perform indirect standardization and derive the age-standardized mortality rates for the states for comparison. In addition, we derived a ratio for age-standardized mortality to compare across age groups within the state. We extracted information regarding COVID-19 deaths from the Integrated Disease Surveillance Programme special surveillance portal up to November 16, 2020.

Results

The crude mortality rate of India stands at 88.9 per million population(118,883/1,337,328,910). Age-adjusted mortality rate (per million) was highest for Delhi (300.5) and lowest for Kerala (35.9).The age-standardized mortality rate (per million) for India is (<15 years=1.6, 15–29 years=6.3, 30–44 years=35.9, 45– 59 years=198.8, 60–74 years=571.2, ≥75 years=931.6). The ratios for age-standardized mortality increase proportionately from 45-59 years age group across all the states.

Conclusion

There is high COVID-19 mortality not only among the elderly ages, but we also identified heavy impact of COVID-19 on the working population. Therefore, we recommend further evaluation of age-adjusted mortality for all States and inclusion of variables like gender, socio-economic status for standardization while identifying at-risk populations and implementing priority public health actions.
Humoral and cellular responses after a third dose of BNT162b2 vaccine in patients treated for lymphoid malignancies
Authors: Re Daniel , Seitz-Polski Barbara , Carles Michel , Brglez Vesna , Graça Daisy , Benzaken Sylvia , Liguori Stéphane , Zahreddine Khaled , Delforge Margaux , Verrière Benjamin , Chamorey Emmanuel , Jérôme Barrière
Published: July 2021

BACKGROUND

Immunocompromised patients such as patients with hematological malignancies have impaired immune response to two doses of BNT162b2 (Pfizer / BioNtech) vaccine against SARS-CoV-2. Evaluation of a repeated immune stimulation with a third vaccine dose is needed.

METHODS

a vaccine monitoring observatory was conducted in outpatients who were treated for lymphoid malignancies (LM) to monitor both immune and cellular response measured the day of administration of the dose 3 of the mRNA vaccine BNT162b2 and again three to four weeks. Elecsys ® Anti-SARS-CoV-2 immunoassay was used to asses to the level of SARS-CoV-2 anti-Spike (S) antibodies (Abs) titer and SARS-CoV-2-specific T-cell responses were assessed by a whole blood Interferon-Gamma Release Immuno Assay (IGRA) (QuantiFERON Human IFN-gamma SARS-CoV-2, Qiagen®).

RESULTS

Among the 43 assessable patients (suffering from chronic lymphocytic leukemia (CLL) (n=15), indolent and aggressive B cell non-Hodgkin lymphoma (NHL) (n=14), and multiple myeloma (MM) (n=16)), 18 (41,8%) had no anti-S Abs before the dose 3 of BNT162b2 vaccine (n=9 CLL, n=8 NHL, n=1 MM), and they all 18 remained negative after the dose 3. Amongst the 25 patients with positive anti-S titers before dose 3, all patients remained positive and 23 patients increased their anti-S titer after dose 3. Patients with CLL and/or with previous anti-CD20 therapy treated within 12 months of administration of dose 3 had no significant increase of the humoral response. Among 22 available patients, dose 3 of BNT162b2 vaccine significantly increased the median IFN-gamma secretion. On eight (36.4%) patients who were double-negative for both immune and cellular response, five (22.7%) patients remained double-negative after dose 3.

CONCLUSIONS

Dose 3 of BNT162b2 vaccine stimulated humoral immune response among patients with LM, in particular patients with MM (who had higher anti-S baseline titer after dose 2) and those with no anti-CD20 treatment history within a year. T-cell response was increased among patients in particular with no active chemotherapy regimen. Our data support the use of an early third vaccine dose among immunocompromised patients followed for LM though some of them will still have vaccine failure.
Clinical and Virological Response to a Neutralizing Monoclonal Antibody for Hospitalized Patients with COVID-19
Authors:   ACTIV-3/TICO Bamlanivimab Study Group, Lundgren Jens D. , Grund Birgit , Barkauskas Christina E. , Holland Thomas L. , Gottlieb Robert L. , Sandkovsky Uriel , Brown Samuel M. , Knowlton Kirk U. , Self Wesley H. , Files D. Clark , Jain Mamta K. , Benfield Thomas , Bowdish Michael E. , Leshnower Bradley G. , Baker Jason V. , Jensen Jens-Ulrik , Gardner Edward M. , Ginde Adit A. , Harris Estelle S. , Johansen Isik S. , Markowitz Norman , Matthay Michael A. , Østergaard Lars , Chang Christina C. , Goodman Anna , Chang Weizhong , Dewar Robin L. , Gerry Norman P. , Higgs Elizabeth S. , Highbarger Helene , Murray Daniel D. , Murray Thomas A. , Natarajan Ven , Paredes Roger , Parmar Mahesh K.B. , Phillips Andrew N. , Reilly Cavan , Rupert Adam W. , Sharma Shweta , Shaw-Saliba Kathryn , Sherman Brad T. , Teitelbaum Marc , Wentworth Deborah , Cao Huyen , Klekotka Paul , Babiker Abdel G. , Davey Victoria J. , Gelijns Annetine C. , Kan Virginia L. , Polizzotto Mark N. , Thompson B. Taylor , Lane H. Clifford , Neaton James D.
Published: July 2021

BACKGROUND

Bamlanivimab, a neutralizing monoclonal antibody given in combination with remdesivir, did not improve outcomes among hospitalized COVID-19 patients based on an early futility assessment. In this final study report, we evaluate an a priori hypothesis that greater benefit of bamlanivimab would be identified in those without detectable endogenous neutralizing antibody levels at study entry, especially if viral levels were high.

METHODS

Hospitalized COVID-19 patients were randomized to receive bamlanivimab (7000mg) or placebo and followed for 90 days for sustained recovery (home for 14 consecutive days); recovery rate ratios (RRRs) are cited.

RESULTS

Among 314 participants (163 on bamlanivimab and 151 on placebo), the median time to sustained recovery was 19 days and RRR=0.99 (95% CI: 0.79-1.22; p=0.89). At entry, 50% evidenced production of anti-spike neutralizing antibodies; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels ≥ 1,000 ng/L. Among those without and with antibodies at study entry, the RRRs were 1.24 (95% CI: 0.90-1.70) and 0.74 (95% CI: 0.54-1.00) (p=0.02 for interaction). The RRRs were elevated for those with plasma antigen or nasal viral RNA levels above versus below median at entry, and was greatest for those without antibodies and with elevated antigen or viral RNA levels: 1.48 (95% CI: 0.99-2.23), 1.94 (1.25-3.00), respectively (p<0.05 for all interactions). Hazard ratios for safety outcomes also differed by serostatus at entry.

CONCLUSIONS

Sustained recovery after administration of bamlanivimab versus placebo differed by presence of neutralizing antibodies at study entry, especially if participants had markers of elevated viral replication.

ClinicalTrials.gov number, NCT04501978.
Antibody responses to BNT162b2 vaccination in Japan: Monitoring vaccine efficacy by measuring IgG antibodies against the receptor binding domain of SARS-CoV-2
Authors: Fujigaki Hidetsugu , Yamamoto Yasuko , Koseki Takenao , Banno Sumi , Ando Tatsuya , Ito Hiroyasu , Fujita Takashi , Naruse Hiroyuki , Hata Tadayoshi , Moriyama Saya , Takahashi Yoshimasa , Suzuki Tadaki , Murakami Takahiro , Yoshida Yukihiro , Yagura Yo , Oyamada Takayoshi , Takemura Masao , Kondo Masashi , Iwata Mitsunaga , Saito Kuniaki
Published: July 2021

BACKGROUND

To fight severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), mass vaccination has begun in many countries. To investigate the usefulness of a serological assay to predict vaccine efficacy, we analyzed the levels of IgG, IgM, and IgA against the receptor binding domain (RBD) of SARS-CoV-2 in the sera from BNT162b2 vaccinated individuals in Japan.

METHODS

This study included 219 individuals who received two doses of BNT162b2. The levels of IgG, IgM, and IgA against RBD were measured by enzyme-linked immunosorbent assay before and after the first and second vaccination, respectively. The relationship between antibody levels and several factors including age, gender, and hypertension were analyzed. Virus-neutralizing activity in sera was measured to determine the correlation with the levels of antibodies. A chemiluminescent enzyme immunoassay (CLEIA) method to measure IgG against RBD was developed and validated for the clinical setting.

RESULTS

The levels of all antibody isotypes were increased after vaccination. Among them, RBD-IgG was dramatically increased after the second vaccination. The IgG levels in females were significantly higher than in males. There was a negative correlation between age and IgG levels in males. The IgG levels significantly correlated with the neutralizing activity. The CLEIA assay measuring IgG against RBD showed a reliable performance and a high correlation with neutralizing activity.

CONCLUSIONS

Monitoring of IgG against RBD is a powerful tool to predict the efficacy of SARS-CoV-2 vaccination and provides useful information in considering a personalized vaccination strategy for COVID-19.
Fairness in Cardiac Magnetic Resonance Imaging: Assessing Sex and Racial Bias in Deep Learning-based Segmentation
Authors: Puyol-Antón Esther , Ruijsink Bram , Harana Jorge Mariscal , Piechnik Stefan K. , Neubauer Stefan , Petersen Steffen E. , Razavi Reza , Chowienczyk Phil , King Andrew P
Published: July 2021

Background

Artificial intelligence (AI) techniques have been proposed for automation of cine CMR segmentation for functional quantification. However, in other applications AI models have been shown to have potential for sex and/or racial bias.

Objectives

To perform the first analysis of sex/racial bias in AI-based cine CMR segmentation using a large-scale database.

Methods

A state-of-the-art deep learning (DL) model was used for automatic segmentation of both ventricles and the myocardium from cine short-axis CMR. The dataset consisted of end-diastole and end-systole short-axis cine CMR images of 5,903 subjects from the UK Biobank database (61.5±7.1 years, 52% male, 81% white). To assess sex and racial bias, we compared Dice scores and errors in measurements of biventricular volumes and function between patients grouped by race and sex. To investigate whether segmentation bias could be explained by potential confounders, a multivariate linear regression and ANCOVA were performed.

Results

We found statistically significant differences in Dice scores (white ∼94% vs minority ethnic groups 86-89%) as well as in absolute/relative errors in volumetric and functional measures, showing that the AI model was biased against minority racial groups, even after correction for possible confounders.

Conclusions

We have shown that racial bias can exist in DL-based cine CMR segmentation models. We believe that this bias is due to the imbalanced nature of the training data (combined with physiological differences). This is supported by the results which show racial bias but not sex bias when trained using the UK Biobank database, which is sex-balanced but not race-balanced.

Condensed Abstract

AI algorithms have the potential to reflect or exacerbate racial/sex disparities in healthcare. We aimed to determine the impact of sex and race on the performance of an AI segmentation model for automatic CMR quantification in a cohort of 5,903 subjects from the UK Biobank database, which is sex-balanced but not race-balanced. We tested the model’s bias in performance using Dice scores and absolute/relative errors in measurements of biventricular volumes and function. Our study demonstrates that the model had a racial bias but no sex bias, and that subject characteristics and co-morbidities could not explain this bias.
Transcriptional and Post-transcriptional Regulation of Ethylene Biosynthesis by Salicyclic Acid in Kiwifruit
Authors: Wang Jian , Liu Xiao-fen , Wang Wen-qiu , Zhang Hui-qin , Yin Xue-ren
Published: July 2021

Levels of ethylene, implicated in a diverse array of plants for inducing fruit ripening, is influenced by genetic and environmental factors, such as the other plant hormones. Among these, salicylic acid (SA) has been demonstrated to inhibit ethylene biosynthesis in fruit, yet the underlying regulatory mechanisms remains elusive. Here, we showed that treatment with exogenous ASA (acetylsalicylic acid) dramatically reduced ethylene production, as well as activities of ACC synthase (ACS) and ACC oxidase (ACO), in kiwifruit tissues. Comparative transcriptome analysis indicated the differential expression of ethylene biosynthetic genes (AdACS1/2 and AdACO5). A screen of transcription factors indicated that AdERF105L and AdWRKY29 were ASA-responsive regulators of AdACS1/2 and AdACO5, respectively. In addition to these genes, AdACS3 and AdACO3 were abundantly expressed in both ASA-treated and control tissues. AdACS3 protein was phosphorylated and stabilized by AdMPK16, a mitogen-activated protein kinase; while AdACO3 activity was enhanced by AdAP, an aspartic peptidase. Exogenous ASA down-regulated AdMPK16 and AdAP, thereby influencing ethylene biosynthesis at a post-transcriptional level. These findings propose a multidimensional system for SA-inhibition on ethylene biosynthesis, inducing differential expression of some ethylene biosynthesis genes, as well as differential effects on protein activity on other targets.

Involvement of transcription factors, protein kinase and aspartic peptidase in synergistically regulating salicylic acid-induced ethylene decrease in kiwifruit flesh
IT ambidexterity driven patient agility and hospital patient service performance: a variance approach
Authors: van de Wetering Rogier
Published: July 2021

Hospitals are currently exploring digital options to transform their clinical procedures and their overall engagement with patients. This paper investigates how hospital departments can leverage the ability of firms to simultaneously explore new IT resources and practices (IT exploration) as well as exploit their current IT resources and practices (IT exploitation), i.e., IT ambidexterity, to adequately sense and respond to patients’ needs and demands, i.e., patient agility. This study embraces the dynamic capability view and develops a research model, and tests it accordingly using cross-sectional data from 90 clinical hospital departments from the Netherlands through an online survey. The model’s hypothesized relationships are tested using Partial Least Squares (PLS) structural equation modeling (SEM). The outcomes demonstrate the significance of IT ambidexterity in developing patient agility, positively influencing patient service performance. The study outcomes support the theorized model can the outcomes shed light on how to transform clinical practice and drive patient agility.
Performance of a machine learning model in recognition of normal tissue from histological sections
Authors: Sanyal Parikshit , Paul Sayak , Das Avinash
Published: July 2021

Introduction

Machine learning and artificial intelligence (AI) models have been applied in histopathology to solve specific problems like detection of metastasis in lymph nodes and immunohistochemical scoring. We have aimed to develop a machine learning model which can be trained in histopathology from the basics, i.e. identification of normal tissue. We have tried to replicate the process through which a human pathologist learns recognition of normal tissue from histological sections, and evaluate the performance of a machine learning model at this task.

Materials and methods

A total of 658 histologic images were anonymised, microphotographed at 10x magnification, under the same condition of illumination, with a Magnus DC5 integrated microphotography system. The images were split into two subsets, training (386) and validation (272 images). The images belonged to seven classes of tissue: brain, intestine, kidney, liver, lungs, muscle and skin. Archived material of the hospital were used for the study. A machine learning model using convolutional neural network (CNN) was developed on the Keras platform, using the convolution layers of a pretrained VGG16 model. The model was trained with the training set of images over 10 epochs. After training, performance of the model was assessed on the validation set.

Results

The model achieved 88.24% accuracy in classifying the images of the validation set. The most frequent errors were met in recognising images of kidney (14 errors, 33.33%). The commonest error was wrongly classifying kidney tissue as liver (07 errors). Analysis of the deeper layers of the neural network revealed specific patterns in images which were wrongly classified.

Conclusion

The results of the present study indicates that a convolutional neural network might be trained in histology similar to a trainee pathologist. The study represents the first step towards developing a machine learning model as a generalised histopathological image classifier.
Degradation of Red Blood Cell Deformability during Cold Storage in Blood Bags
Authors: Islamzada Emel , Matthews Kerryn , Lamoureux Erik , Duffy Simon P. , Scott Mark D. , Ma Hongshen
Published: July 2021

Red blood cells (RBCs) stored in blood bags develop a storage lesion that include structural, metabolic, and morphologic transformations resulting in a progressive loss of RBC deformability. The speed of RBC deformability loss is donor-dependent, which if properly characterized, could be used as a biomarker to select high-quality RBC units for sensitive recipients or to provide customized storage timelines depending on the donor. We used the microfluidic ratchet device to measure the deformability of red blood cells stored in blood bags every 14 days over a span of 56 days. We observed that storage in blood bags generally prevented RBC deformability loss over the current standard 42-day storage window. However, between 42 and 56 days, the deformability loss profile varied dramatically between donors. In particular, we observed accelerated RBC deformability loss for a majority of male donors, but for none of the female donors. Together, our results suggest that RBC deformability loss could be used to screen for donors who can provide stable RBCs for sensitive transfusion recipients or to identify donors capable of providing RBCs that could be stored for longer than the current 42-day expiration window.
Displacement statistics of unhindered single molecules show no enhanced diffusion in enzymatic reactions
Authors: Choi Alexander A. , Park Ha H. , Chen Kun , Yan Rui , Li Wan , Xu Ke
Published: July 2021

Recent studies have sparked heated debate over whether catalytical reactions would enhance the diffusion coefficients D of enzymes. Through high statistics of the transient (600 μs) displacements of unhindered single molecules freely diffusing in common buffers, we here quantify D for four highly contested enzymes under catalytic turnovers. We thus formulate how precisions of better than ±1% may be achieved for D at the 95% confidence level, and show no changes in diffusivity for catalase, urease, aldolase, and alkaline phosphatase under the application of wide concentration ranges of substrates. Our single-molecule approach thus overcomes potential limitations and artifacts underscored by recent studies to show no enhanced diffusion in enzymatic reactions.

Table of Contents artwork
A neural signature of automatic lexical access in bilinguals
Authors: Aristei Sabrina , Lochy Aliette , Rossion Bruno , Schiltz Christine
Published: July 2021

Bilingualism is often associated with beneficial effects on cognitive control and top-down processes. The present study aimed at bypassing these processes to assess automatic visual word recognition in bilinguals. Using fast periodic visual stimulation, we recorded frequency-tagged word-selective EEG responses in French monolinguals and late bilinguals (German native, French as second language). Words were presented centrally within rapid (10 Hz) sequences of letter strings varying in word-likeness, i.e., consonant strings, non-words, pseudo-words, while participants performed an orthogonal task. Automatic word-selective brain responses in the occipito-temporal cortex arose almost exclusively for the languages mastered by participants: two in bilinguals vs. one in monolinguals. Importantly, the amplitude of bilinguals’ responses to words within consonant strings were unaffected by the native vs. late-learnt status of the language. Furthermore, for all and only known languages, word-selective responses were reduced by embedding them in pseudo-words relative to non-words, both derived from the same language as the words. This word-likeness effect highlights the lexical nature of the recorded brain visual responses. A cross-language word-likeness effect was observed only in bilinguals and only with pseudo-words derived from the native language, indicating an experience-based tuning to language. Taken together these findings indicate that the amount of exposure to a language determines the engagement of neural resources devoted to word processing in the occipito-temporal visual cortex. We conclude that automatic lexical coding occurs at early visual processing in bilinguals and monolinguals alike, and that language exposure determines the competition strength of a language.

Significance Statement

Bilingualism and its possible impact on automatic processes have rarely attracted interest, contrary to bilingualism and its mutual relation with the executive functions. We assessed automatic visual word recognition in bi- and monolingual individuals while purposively bypassing executive functions. Visual brain potentials frequency tagged to words, that were flashed in rapid trains of strings with varying word-likeness degrees, exposed the automatic encoding of word-form as well as language identity at early stages of visual word processing within the occipito-temporal visual cortex. The mechanisms involved in both encoding processes reflect experience-based activity as the one characterizing tight-tuned neurons in the VWFA. Our findings provide a novel framework to understand the mechanisms behind the incredible efficiency of bilinguals in handling multiple languages.
Escaping the Fate of Sisyphus: Assessing Resistome Hybridization Baits for Antimicrobial Resistance Gene Capture
Authors: Beaudry Megan S. , Thomas Jesse C. , Baptista Rodrigo , Sullivan Amanda , Norfolk William , Devault Alison , Enk Jacob , Kieran Troy J. , Rhodes Olin , Perry Allison , Rose Laura , Bayona-Vásquez Natalia J. , Oladeinde Ade , Lipp Erin , Sanchez Susan , Glenn Travis C.
Published: July 2021

Finding, characterizing, and monitoring reservoirs for antimicrobial resistance (AMR) is vital to protecting public health. Hybridization capture baits are an accurate, sensitive, and cost-effective technique used to enrich and characterize DNA sequences of interest, including antimicrobial resistance genes (ARGs), in complex environmental samples. We demonstrate the continued utility of a set of 19,933 hybridization capture baits designed from the Comprehensive Antibiotic Resistance Database (CARD)v1.1.2 and Pathogenicity Island Database (PAIDB)v2.0, targeting 3,565 unique nucleotide sequences that confer resistance. We demonstrate the efficiency of our bait set on a custom-made resistance mock community and complex environmental samples to increase the proportion of on-target reads as much as >200-fold. However, keeping pace with newly discovered ARGs poses a challenge when studying AMR, because novel ARGs are continually being identified and would not be included in bait sets designed prior to discovery. We provide imperative information on how our bait set performs against CARDv3.3.1, as well as a generalizable approach for deciding when and how to update hybridization capture bait sets. This research encapsulates the full life cycle of baits for hybridization capture of the resistome from design and validation (both in silico and in vitro) to utilization and forecasting updates and retirement.

Originality-Significance Statement

This work is applicable to a wide range of research. It helps to define conditions under which hybridization capture is useful regarding not only antimicrobial resistance specifically, but also more generally how to assess the ongoing utility of existing bait sets - giving objective criteria for when and by what strategies baits should be updated. We also provide a method for quantifying and comparing antimicrobial resistance genes (ARGs) similar to what is used for RNAseq experiments. This approach improves comparison of ARGs across environments. Thus, the work provides an improved foundation for ARG future studies, while cutting across traditional areas of microbiology and extending beyond.
cLoops2: a full-stack comprehensive analytical tool for chromatin interactions
Authors: Cao Yaqiang , Liu Shuai , Ren Gang , Tang Qingsong , Zhao Keji
Published: July 2021

Investigating chromatin interactions between regulatory regions such as enhancer and promoter elements is vital for a deeper understanding of gene expression regulation. The emerging 3D mapping technologies focusing on enriched signals such as Hi-TrAC/TrAC-looping, compared to Hi-C and variants, reduce the sequencing cost and provide higher interaction resolution forcis-regulatory elements. A robust pipeline is needed for the comprehensive interpretation of these data, especially for loop-centric analysis. Therefore, we have developed a new versatile tool named cLoops2 for the full-stack analysis of the 3D chromatin interaction data. cLoops2 consists of core modules for peak-calling, loop-calling, differentially enriched loops calling and loops annotation. Additionally, it also contains multiple modules to carry out interaction resolution estimation, data similarity estimation, features quantification and aggregation analysis, and visualization. cLoops2 with documentation and example data are open source and freely available at GitHub:https://github.com/YaqiangCao/cLoops2.
Priority effects among amphibian microbes lead to varying levels of Bd infection
Authors: Barnes Elle M. , Lewis J.D.
Published: July 2021

Priority effects in host-associated microbiomes can influence not only community composition and structure, but also community functions, such as disease resistance. However, evidence for these priority effects remains scarce. Past studies suggest that amphibian protection from chytridiomycosis, caused by the pathogenic fungus Batrachochytrium dendrobatidis (Bd), is related to antifungal bacterial composition on host skin. Priority effects in these bacterial communities may influence susceptibility to Bd, but this possibility has not been tested. Using in vitro microcosms, we demonstrated that priority effects can influence interactions among amphibian-associated microbes. We observed strong priority effects irrespective of high antifungal ability such that the Bd-inhibitory potential of two strongly inhibitory bacterial species did not always produce higher levels of Bd-inhibition. This result suggests that interactions may be more complex than previously thought. Additionally, our results suggest that priority effects between commensal and pathogenic taxa can be either facilitatory or inhibitory, with the strength and direction of this effect dependent on the composition of the community. Thus, changes in assembly may lead to varying levels of Bd infection, influencing how we might augment amphibian-associated microbiomes to conserve taxa currently at risk of extinction.
Uncertainty modulates visual maps during non-instrumental information demand
Authors: Li Yvonne , Daddaoua Nabil , Horan Mattias , Gottlieb Jacqueline
Published: July 2021

Animals are intrinsically motivated to resolve uncertainty and predict future events. This motivation is encoded in cortical and subcortical structures, but a key open question is how it generates concrete policies for attending to informative stimuli. We examined this question using neural recordings in the monkey lateral intraparietal area (LIP), a visual area implicated in attention and gaze, during non-instrumental information demand. We show that the uncertainty that was resolved by a visual cue enhanced visuo-spatial responses of LIP cells independently of reward probability. This enhancement was independent of immediate saccade plans but correlated with the sensitivity to uncertainty in eye movement behavior on longer time scales (across sessions/days). The findings suggest that topographic visual maps receive motivational signals of uncertainty, which enhance the priority of informative stimuli and the likelihood that animals will orient to the stimuli to reduce uncertainty.
The gut microbiome is associated with cocaine behavior and predicts addiction vulnerability in adult male rats
Authors: Suess Gregory J , Kasiah Jennysue , Simpson Sierra , Brennan Molly , Conlisk Dana , Maturin Lisa , George Olivier L , Chassaing Benoit , Frantz Kyle J
Published: July 2021

The gut-brain axis is a bi-directional communication system through which microbial communities in the gut interact with the nervous system, perhaps influencing neuropsychiatric disorders such as drug abuse. This study used behavioral data and biological samples from the Cocaine Biobank to test the hypothesis that the gut microbiota can predict and reflect susceptibility to cocaine reinforcement. Adult male heterogenous rats were catheterized and allowed to self-administer cocaine in short-access sessions (2 hr/day, 10 days, 0.5 mg/kg per intravenous infusion), followed by progressive ratio (PR) tests, long-access sessions (6 hr/day, 14 days), and alternating blocks of PR, long-access, and footshock testing. Fecal samples were collected at three time points and bacterial 16s rRNA genes were sequenced to profile the microbiota. As expected, cocaine-related behavior varied among subjects, such that a quartile split identified low and high responders on each measure, as well as an overall addiction index. Although beta diversity in the microbiota at baseline and after short access did not predict membership in high or low addiction quartiles, linear discriminant analysis (LDA) identified taxa that were more robustly represented in low or high responders. Beta diversity after long access was different among quartiles, as were several specific taxa. Investigation of baseline differences revealed that high relative abundance of Akkermansia muciniphila predicted future low response rates, whereas Ruminococcaceae predicted high response. This study is the first to report that microbiota variability reflects levels of cocaine intake and that microbial profiles might facilitate diagnosis and identify risk factors predictive of drug vulnerability.

Significance Statement

Microbial organisms inhabiting the gut of animals appear to influence organismal function through various signaling pathways, ultimately affecting behavior and disease vulnerability. This experiment investigates links between gut bacteria and vulnerability to addiction-related behaviors in adult male rats. Not only did gut bacterial profiles change as a result of cocaine intake but also gut bacterial profiles before any exposure to cocaine predicted which animals would be high or low addiction-prone individuals. These results suggest that microbial profiles might facilitate diagnosis and identify risk factors predictive of drug addiction.
Abundance of Nef and p-Tau217 in brains of individuals diagnosed with HIV-associated neurocognitive disorders correlate with disease severance
Authors: Pushkarsky Tatiana , Ward Adam , Sviridov Dmitri , Bukrinsky Michael I
Published: July 2021

HIV-associated neurological disorders (HAND) is a term used to describe a variety of neurological impairments observed in HIV-infected individuals. The pathogenic mechanisms of HAND and its connection to HIV infection remain unknown. The brain samples from HIV-infected individuals, both with and without HAND, were characterized by increased abundance of p-Tau217 peptide, which correlated with the abundance of flotillin 1, a marker of lipid rafts. HIV-1 Nef was detected in some, but not all, samples from HAND-affected individuals. Samples positive for Nef had lower abundance of cholesterol transporter ABCA1, higher abundance of flotillin 1 and p-Tau217, and were obtained from individuals with higher severity of HAND relative to Nef-negative samples. These results highlight the contribution of Nef and Nef-dependent effects on cholesterol metabolism and lipid rafts to the pathogenesis of HAND and support a connection between pathogenesis of HAND and Alzheimer’s disease.