bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful early use of anti‐SARS‐CoV‐2 monoclonal neutralizing antibodies in SARS‐CoV‐2 infected hematological patients – A Czech multicenter experience
Authors: Weinbergerová Barbora , Demel Ivo , Víšek Benjamin , Válka Jan , Čerňan Martin , Jindra Pavel , Novák Jan , Stejskal Lukáš , Kovácsová Flóra , Kabut Tomáš , Szotkowski Tomáš , Hájek Roman , Žák Pavel , Cetkovský Petr , Král Zdeněk , Mayer Jiří
Published: February 2022

COVID‐19 significantly impairs survival rates among hematological patients when compared to the general population. Our prospective multicentre project analyzed early administration of anti‐SARS‐CoV‐2 spike protein neutralizing monoclonal antibodies (NmAbs) – bamlanivimab (72%) and casirivimab/imdevimab (28%) – efficacy among hematological patients with early‐stage COVID‐19. Mortality rate was compared to a control cohort of 575 SARS‐CoV‐2 positive hematological patients untreated with any specific anti‐COVID‐19 therapy. 88 hematological patients with lymphomas, acute leukemias, and myeloma as their most frequent underlying diagnoses (72%) were evaluated with a 97 days median follow‐up after NmAb administration. One third of patients (32%) were treated with an anti‐CD20 monoclonal antibody before COVID‐19 diagnosis. Median time between first COVID‐19 symptom and NmAb administration was 2 days. When administering NmAb, 29%, 57%, 11%, 2%, and 1% of our patients had asymptomatic, mild, moderate, severe, and critical degrees of COVID‐19, respectively. 80% of baseline asymptomatic patients remained asymptomatic following NmAb administration. Median duration of COVID‐19 symptoms after NmAb administration was 2.5 days. Progression to severe/critical COVID‐19 occurred among a total of 17% (15/88) of our cases and numerically higher with bamlanivimab versus casirivimab/imdevimab (21% vs. 8%; p = 0.215), and myelomas (29%), lymphomas (17%) and acute leukemias (18%), respectively. During final follow‐up, nine deaths (10%) were recorded ‐ all after bamlanivimab (p = 0.056) with 8% attributed to COVID‐19. Regarding “remdesivir/convalescent plasma naïve” patients, COVID‐19 mortality rates were significantly lower in our NmAbs treated cohort compared to the control cohort of untreated SARS‐CoV‐2 positive hematological patients (6% vs. 16%, p = 0.020), respectively. Our study validated the safety and efficacy of NmAbs early use among hematological patients with newly diagnosed early‐stage COVID‐19 in terms of alleviating infection course and decreasing mortality. Results confirmed a more positive effect of a casirivimab/imdevimab combination versus bamlanivimab monotherapy.
Analysis of responses of the health care workers recovered from COVID‐19 on convalescent plasma donation by apheresis: A single‐center survey study
Authors: Sahu Ansuman , Prakash Satya , Singh Arvind Kumar , Mukherjee Somnath
Published: February 2022

Background

The COVID‐19 convalescent plasma (CCP) has been tried as a therapy in moderate COVID‐19 pneumonia. Donation of CCP requires motivation from recovered patients. This study evaluated the response of such recovered health care workers (HCWs) when they were motivated for CCP donation.

Methods

An interview‐based survey was carried out with recovered HCWs as study participants between August 2020 and November 2020. A qualified social worker explained the details of CCP donation over a mobile call; he clarified all their doubts and motivated them for the plasma donation. Their responses were recorded as “interested” or “not interested” followed by analysis.

Results

We tried to call 624 recovered HCWs, but could not reach 213, and the final group available for the study was 411 participants. Of these 411, 186 were deferred. Finally, we analyzed a total of 225 responses. Eventually, 105 out of 225 HCWs (47%) were interested; there were no significant differences in responses among males and females and between different age groups (<.001) and the “doctors” designation category (P = .01) had a maximum number of “interested” responses. In multivariate logistic regression, only the “interested” responses of the doctors were significantly higher after adjusting the confounding effect of the “graduate and above” educational qualification category.

Conclusion

This study found that nearly half of the eligible HCWs were interested in CCP donation. The educational qualification and designation among the recovered HCWs had an impact on CCP donation interest. The doctors were more interested in CCP donation compared to others.
Reference intervals for coagulation tests in adults with different ABO blood types
Authors: Chen Zeliang , Dai Xiaoqing , Cao Jing , Tan Xuerui , Chen Shuying , Yu Min
Published: February 2022

Introduction

Coagulation tests are affected by many factors, such as age, race, and gestation. Although coagulation test results vary by ABO blood type, reference intervals of different ABO blood groups remain to be determined. This study aims to investigate the reference ranges of coagulation tests for different ABO blood groups in the Han population in South China.

Methods

A retrospective study was conducted in the First Affiliated Hospital of Shantou University Medical College. In all, 9600 individuals aged between 20 and 79 years were included. Coagulation tests, including prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), thrombin time, and fibrinogen, were performed.

Results

There was a significant difference in PT, INR, and aPTT among ABO blood groups. PT and INR varied slightly between ABO blood groups. There was a higher aPTT value in individuals in the O blood group than in those in non‐O blood groups, in both males and females across the included age range. No differences were found in thrombin time and fibrinogen between the ABO blood groups.

Conclusion

The study provides reference data on coagulation tests from ABO blood groups in South China. The established reference intervals specific to ABO blood type, sex, and age may improve clinical decisions based on coagulation tests.
The correlation of D‐dimer to stroke diagnosis within 24 hours: A meta‐analysis
Authors: Ahmad Adeel , Islam Zara , Manzoor Ahmad Saad , Sarfraz Zouina , Sarfraz Azza , Felix Miguel , Cherrez‐Ojeda Ivan
Published: February 2022

Background

Diagnosing D‐Dimer early is essential to optimize clinical treatment and quality of life and reduce mortality. This study aims to identify the difference of D‐Dimer levels (ng/ml) in patients with stroke within the 6‐ and 24‐h period compared to patients that mimic stroke.

Methods

An electronic database search across PubMed/MEDLINE, Cochrane, Web of Science, CINAHL, EMBASE, and Scopus was conducted until December 10, 2021. Studies were eligible if they included adult patients with stroke compared to stroke mimics or controls reporting D‐Dimer values. Quality assessment was conducted using GRADE. The standardized mean difference and 95% confidence intervals were calculated in addition to the difference of means in the crude form. Heterogeneity was assessed using Cochran's Q statistic and the I2 index. A random‐effects model was used. The statistical analysis was conducted using RevMan 5.4.

Results

Out of 2901, there were 318 (11%) participants from upper‐middle‐income countries, whereas the others were from high‐income countries. Large positive effect size was found for D‐Dimer in the stroke group (Cohen's d = 2.82 [1.73–3.9]; p < 0.00001), meaning that those with stroke had higher D‐Dimer values on presentation compared to the stroke mimics/controls. A large difference in means was found in the two groups (MD = 685.1 [324.2, 1045.99]; p < 0.00001), suggesting that there was a significantly higher laboratory value in the stroke group.

Conclusion

Our findings must be used in caution as the most reliable diagnostic tests for stroke are CT and MRI. Laboratory testing such as D‐Dimer values is a valuable clinical adjuvant in diagnosing total stroke.
Oxidative and glycolytic skeletal muscles deploy protective mechanisms to avoid atrophy under pathophysiological iron overload
Authors: Martin David , Nay Kévin , Robin François , Rebillard Amélie , Orfila Luz , Martin Brice , Leroyer Patricia , Guggenbuhl Pascal , Dufresne Suzanne , Noirez Philippe , Ropert Martine , Loréal Olivier , Derbré Frédéric
Published: February 2022

Background

Iron excess has been proposed as an essential factor in skeletal muscle wasting. Studies have reported correlations between muscle iron accumulation and atrophy, either through ageing or by using experimental models of secondary iron overload. However, iron treatments performed in most of these studies induced an extra‐pathophysiological iron overload, more representative of intoxication or poisoning. The main objective of this study was to determine the impact of iron excess closer to pathophysiological conditions on structural and metabolic adaptations (i) in differentiated myotubes and (ii) in skeletal muscle exhibiting oxidative (i.e. the soleus) or glycolytic (i.e. the gastrocnemius) metabolic phenotypes.

Methods

The impact of iron excess was assessed in both in vitro and in vivo models. Murine differentiated myotubes were exposed to ferric ammonium citrate (FAC) (i.e. 10 and 50 μM) for the in vitro component. The in vivo model was achieved by a single iron dextran subcutaneous injection (1 g/kg) in mice. Four months after the injection, soleus and gastrocnemius muscles were harvested for analysis.

Results

In vitro, iron exposure caused dose‐dependent increases of iron storage protein ferritin (P < 0.01) and dose‐dependent decreases of mRNA TfR1 levels (P < 0.001), which support cellular adaptations to iron excess. Extra‐physiological iron treatment (50 μM FAC) promoted myotube atrophy (P = 0.018), whereas myotube size remained unchanged under pathophysiological treatment (10 μM FAC). FAC treatments, whatever the doses tested, did not affect the expression of proteolytic markers (i.e. NF‐κB, MurF1, and ubiquitinated proteins). In vivo, basal iron content and mRNA TfR1 levels were significantly higher in the soleus compared with the gastrocnemius (+130% and +127%; P < 0.001, respectively), supporting higher iron needs in oxidative skeletal muscle. Iron supplementation induced muscle iron accumulation in the soleus and gastrocnemius muscles (+79%, P < 0.001 and +34%, P = 0.002, respectively), but ferritin protein expression only increased in the gastrocnemius (+36%, P = 0.06). Despite iron accumulation, muscle weight, fibre diameter, and myosin heavy chain distribution remained unchanged in either skeletal muscle.

Conclusions

Together, these data support that under pathophysiological conditions, skeletal muscle can protect itself from the related deleterious effects of excess iron.
Is a decrease in activities of daily living in the elderly irreversible? A case report of Wernicke encephalopathy in home medical care
Authors: Onizawa Nobuyuki , Ishida Mayumi , Uchida Nozomu , Sato Izumi , Yoshioka Akira , Ito Hiroshi , Onishi Hideki
Published: February 2022

The patient was an 83‐year‐old male who, after being hospitalized for 70 days for suffocation due to aspiration, was provided with home medical care (HMC) as his physical condition did not allow him to climb stairs. Wernicke encephalopathy (WE) was suspected based on his disorientation and a continued loss of appetite. This diagnosis was supported by abnormal serum thiamine and the disappearance of delirium after thiamine administration. In addition, he became able to use stairs. Patients who receive HMC should undergo active screening and receive treatment with WE in mind.
Preliminary Experience of 5.0 T Higher Field Abdominal Diffusion‐Weighted MRI: Agreement of Apparent Diffusion Coefficient With 3.0 T Imaging
Authors: Zhang Yunfei , Yang Chun , Liang Liang , Shi Zhang , Zhu Shuo , Chen Caizhong , Dai Yongming , Zeng Mengsu
Published: February 2022

Background

Recently, a prototype 5.0 T whole‐body MRI scanner was developed. A 5.0 T diffusion‐weighted imaging (DWI) may help overcome the issues that limit 3.0 T DWI.

Purpose

To evaluate the feasibility of 5.0 T high‐field DWI in the upper abdomen and assess the agreement of the apparent diffusion coefficient (ADC) with that from 3.0 T abdominal DWI.

Study type

Prospective proof of concept.

Population

Nine volunteers (mean ± SD age: 37.3 ± 7.0 years, 8 M), eight healthy and one with liver and kidney cysts.

Field strength/Sequence

3.0 T and 5.0 T; respiratory‐triggered spin‐echo echo‐planar‐imaging (SE‐EPI)‐based DWI sequence.

Assessment

Subjective image quality scores. The ADC values in abdominal organs (liver, pancreas, spleen, and kidney) were measured by two observers for evaluating the interobserver and interfield agreement.

Statistical Tests

Wilcoxon‐rank sum test, Bland–Altman analysis, intraclass correlation coefficients (ICCs), and coefficients of variation (CVs).

Results

The 5.0 T DWI displayed an increase in subjective image quality score compared to 3.0 T DWI without the significant difference (3.0 T DWI: 3.50 ± 0.47, 5.0 T DWI: 3.72 ± 0.42, P = 0.157). Both the interfield and interobserver agreements of ADC values were substantial to excellent (ICCs = 0.640–0.902). For all four upper abdominal organs, there were no significant differences between the ADC values measured by two observers and between the ADC values of 3.0 T and 5.0 T DWI (P = 0.134–1.000). The CVs of ADC measurements from 3.0 T and 5.0 T DWI were all less than 15.0% (6.7%–14.2%).

Data Conclusion

The substantial to excellent agreements between the ADC values measured with 3.0 T and 5.0 T DWI for liver, pancreas, spleen, and kidney suggested that 5.0 T DWI can be applied for abdominal imaging. The ADC values from 5.0 T abdominal DWI hold the potential to serve as the quantitative markers for clinical investigations.

Evidence Level

2

Technical Efficacy

Stage 1
Cerebrovascular Effects of Lower Body Negative Pressure at 3T MRI: Implications for Long‐Duration Space Travel
Authors: Kramer Larry A. , Hasan Khader M. , Gabr Refaat E. , Macias Brandon R. , Marshall‐Goebel Karina , Laurie Steven S. , Hargens Alan R.
Published: February 2022

Background

Optic disc edema develops in most astronauts during long‐duration spaceflight. It is hypothesized to result from weightlessness‐induced venous congestion of the head and neck and is an unresolved health risk of space travel.

Purpose

Determine if short‐term application of lower body negative pressure (LBNP) could reduce internal jugular vein (IJV) expansion associated with the supine posture without negatively impacting cerebral perfusion or causing IJV flow stasis.

Study Type

Prospective.

Subjects

Nine healthy volunteers (six women).

Field Strength/Sequence

3T/cine two‐dimensional phase‐contrast gradient echo; pseudo‐continuous arterial spin labeling single‐shot gradient echo echo‐planar.

Assessment

The study was performed with two sequential conditions in randomized order: supine posture and supine posture with 25 mmHg LBNP (LBNP25). LBNP was achieved by enclosing the lower extremities in a semi‐airtight acrylic chamber connected to a vacuum. Heart rate, bulk cerebrovasculature flow, IJV cross‐sectional area, fractional IJV outflow relative to arterial inflow, and cerebral perfusion were assessed in each condition.

Statistical Tests

Paired t‐tests were used to compare measurement means across conditions. Significance was defined as P < 0.05.

Results

LBNP25 significantly increased heart rate from 64 ± 9 to 71 ± 8 beats per minute and significantly decreased IJV cross‐sectional area, IJV outflow fraction, cerebral arterial flow rate, and cerebral arterial stroke volume from 1.28 ± 0.64 to 0.56 ± 0.31 cm2, 0.75 ± 0.20 to 0.66 ± 0.28, 780 ± 154 to 708 ± 137 mL/min and 12.2 ± 2.8 to 9.7 ± 1.7 mL/cycle, respectively. During LBNP25, there was no significant change in gray or white matter cerebral perfusion (P = 0.26 and P = 0.24 respectively) and IJV absolute mean peak flow velocity remained ≥4 cm/sec in all subjects.

Data Conclusion

Short‐term application of LBNP25 reduced IJV expansion without decreasing cerebral perfusion or inducing IJV flow stasis.

Level of Evidence

1

Technical Efficacy Stage

1
Working on the dirty side—the ipsilateral subclavian access for temporary pacing after lead extraction
Authors: Zweiker David , Melillo Francesco , D’Angelo Giuseppe , Radinovic Andrea , Marzi Alessandra , Cianfanelli Lorenzo , Altizio Savino , Limite Luca R. , Paglino Gabriele , Frontera Antonio , Nakajima Kenzaburo , Brugliera Luigia , Malatino Lorenzo , Della Bella Paolo , Mazzone Patrizio
Published: February 2022

Background

Temporary pacing is necessary in pacemaker‐dependent patients after transvenous lead extraction (TLE) for cardiac implantable electronic device infection. In case of unavailability of other accesses, we propose to use the ipsilateral subclavian access (ISA) combined with a standard permanent active fixation lead for the temporary pacemaker and present preliminary data.

Methods

We consecutively enrolled patients undergoing TLE who received a temporary pacemaker using the ISA between August 2016 and April 2020 at our centre.

Results

During the observation period, 36 patients undergoing TLE for pocket infection (72.2%), endocarditis (25.0%) or other causes received a temporary pacemaker over the ISA. Their mean age was 77.0 ± 10.7 years, and 13.9% were female. Complete TLE was achieved in 94.4%. There were no major periprocedural complications. Intra‐hospital mortality was 11.1%. Pocket revision was performed in 19.4%. During long‐term follow‐up (23 ± 13 months), 8.3% had a relapse of local pocket infection and 2.8% needed rehospitalization for reintervention.

Conclusions

Temporary pacing using a standard permanent active fixation lead using the ISA is a convenient alternative to conventional venous accesses. However, risks of implanting a lead into a previously infected area have to be taken into account.
A hidden cost of mucus production by phytoplankton: Viscosity hinders nutrient uptake
Authors: Inman Bryce G.
Published: February 2022

Diverse phytoplankton exude polysaccharides that can form a viscous mucus layer surrounding their cells, facilitating complex chemical exchanges with bacteria. An unexplored ramification of mucus production is the influence of its viscosity on the diffusion of nutrients such as vitamins to the cell. Here, I use simulations to demonstrate that mucus viscosity increases the nutrient concentration gradient but always reduces the flux to the cell. Uptake is marginally improved during nutrient pulses, as the mucus acts like a sponge by retaining nutrients near the cell. Lower uptake in the presence of mucus presents a fitness cost that any ecological benefits of mucus must outweigh. I derive a relationship between mucus viscosity and nutrient uptake that can be used to test hypotheses of mutualistic interactions between phytoplankton and bacteria. This work emphasizes the need for empirical measurements of macronutrient diffusion through mucus layers and provides a framework for interpreting those results.
Water‐Soluble Reactive Polymer Blends for Stable Memory Layers in Low‐Voltage Nonvolatile Organic Memory Transistors with High Mobility and Data‐Retention Characteristics
Authors: Lee Chulyeon , Lee Woongki , Kim Hwajeong , Kim Youngkyoo
Published: February 2022

Here low‐voltage nonvolatile organic memory transistors, featuring high charge‐carrier mobility and outstanding data‐retention characteristics, by employing water‐soluble reactive polymer blends as a gate‐insulating memory layer are demonstrated. Blend films of poly(vinyl alcohol) (PVA) and poly(2‐acrylamido‐2‐methyl‐1‐propanesulfonic acid) (PAMPSA) (PVA:PAMPSA) are prepared from their aqueous solutions with various molar ratios of PAMPSA (0–18 mol%) and thermally annealed at 70 and 110 °C. Organic field‐effect transistors (OFETs) are fabricated by depositing poly(3‐hexylthiophene) (P3HT) channel layers on the thermally treated PVA:PAMPSA films. Results show that the hole mobility of OFETs is remarkably increased (≈294 times at 70 °C and ≈42 times at 110 °C) by adding only 2 mol% PAMPSA to the PVA films and further improved at 10 mol% PAMPSA (>11.7 cm2 V−1s−1 at 70 °C and >3.8 cm2 V−1 s−1 at 110 °C). The hysteresis characteristics are rather strengthened for the PVA:PAMPSA layers by annealing at 110 °C due to the formation of cross‐linking sites, even though the OFETs with the pristine PVA layers do almost lose hysteresis characteristics at 110 °C. The optimized OFETs with the PVA:PAMPSA layers (10 mol%, 110 °C) deliver excellent data retention characteristics during >10 000 memory cycles at a voltage range of −5 to +5 V.
Urolithins: a Comprehensive Update on their Metabolism, Bioactivity, and Associated Gut Microbiota
Authors: García‐Villalba Rocío , Giménez‐Bastida Juan Antonio , Cortés‐Martín Adrián , Ávila‐Gálvez María Ángeles , Tomás‐Barberán Francisco A. , Selma María Victoria , Espín Juan Carlos , González‐Sarrías Antonio
Published: February 2022

Urolithins, metabolites produced by the gut microbiota from the polyphenols ellagitannins and ellagic acid, are discovered by the research group in humans almost 20 years ago. Pioneering research suggests urolithins as pleiotropic bioactive contributors to explain the health benefits after consuming ellagitannin‐rich sources (pomegranates, walnuts, strawberries, etc.). Here, this study comprehensively updates the knowledge on urolithins, emphasizing the review of the literature published during the last 5 years. To date, 13 urolithins and their corresponding conjugated metabolites (glucuronides, sulfates, etc.) have been described and, depending on the urolithin, detected in different human fluids and tissues (urine, blood, feces, breastmilk, prostate, colon, and breast tissues). There has been a substantial advance in the research on microorganisms involved in urolithin production, along with the compositional and functional characterization of the gut microbiota associated with urolithins metabolism that gives rise to the so‐called urolithin metabotypes (UM‐A, UM‐B, and UM‐0), relevant in human health. The design of in vitro studies using physiologically relevant assay conditions (molecular forms and concentrations) is still a pending subject, making some reported urolithin activities questionable. In contrast, remarkable progress has been made in the research on the safety, bioactivity, and associated mechanisms of urolithin A, including the first human interventions.
Asynchronous resource‐aware control for uncertain semi‐Markov jump systems with application to robot arm
Authors: Fu Hang , Ma Chao
Published: February 2022

This article investigates the asynchronous controller design of uncertain semi‐Markov jump systems (SMJSs) with a self‐triggered scheme to reduce network resource occupation and attenuate disturbance. More precisely, a self‐triggered strategy is designed for the asynchronous controller synthesis process, which could improve network communication efficiency and deal with the mode jump asynchronous phenomenon problem of systems and controllers. To achieve the desired interference rejection performance of SMJSs, sufficient criteria are constructed in terms of model transformation and mode‐dependent Lyapunov functional method. Then, the matrix technique is used to synthesize asynchronous controller design. Eventually, our proposed approach is validated via a practical illustration on a single‐link robot arm.
Presence of Tim3+ and PD‐1+CD8+T cells identifies microsatellite stable colorectal carcinomas with immune exhaustion and distinct clinicopathological features
Authors: Klapholz Max , Drage Michael G , Srivastava Amitabh , Anderson Ana C
Published: February 2022

Colorectal carcinoma (CRC) is the second leading cause of cancer mortality worldwide. CRC is stratified into two major groups: microsatellite stable (MSS) and microsatellite instability‐high (MSI‐H). MSS CRC constitutes the majority of cases, has worse overall prognosis, and thus far has failed to respond to immunotherapies targeting the immune checkpoint receptors PD‐1, PD‐L1, and CTLA‐4. Here we examined the alternate immunotherapy targets Tim‐3 and Lag‐3, as well as PD‐1, on immune cells in a cohort of MSS CRC using immunohistochemistry and flow cytometry together with mutational analysis and clinical data. We found that PD‐1 was variably expressed across CD4+ tumor‐infiltrating lymphocyte (TIL) subtypes, and Tim‐3 was mostly restricted to CD4+ regulatory T cells. Lag‐3, when detected by flow cytometry, was largely coexpressed with Tim‐3 and PD‐1 in CD4+ TILs. Furthermore, Tim‐3+PD‐1+ CD8+ TILs accumulated in the tumor and exhibited a dysfunctional or ‘exhausted’ phenotype. Notably, we observed a subset of patients with a high proportion of Tim‐3−PD‐1− CD8+ TILs and, conversely, a low proportion of Tim‐3+PD‐1+ CD8+ TILs, thus stratifying MSS CRC patients based on a feature of immune exhaustion (MSS‐ImmEx). MSS‐ImmExhi patients had abundant Tim‐3+PD‐1+ CD8+ TILs, PD‐1+ CD4+ effector, and regulatory T cells, and were enriched for left‐sided colon tumors and mutations in the APC tumor‐suppressor gene. We further investigated the spatial organization of Tim‐3, Lag‐3, PD‐1, and PD‐L1 by immunohistochemistry and found higher levels in the tumor margin; however, MSS‐ImmExhi tumors exhibited a higher density of Tim‐3+ cells in the tumor center over MSS‐ImmExlow tumors. Immunofluorescence revealed a higher density of PD‐1+/CD8+ cells in the tumor center in this group. Our findings identify a subset of MSS CRC that exhibits evidence of higher prior immune activation (MSS‐ImmExhi) in which therapies targeting Tim‐3 in conjunction with anti‐PD‐1 or other immunotherapies may provide clinical benefit. © 2022 The Pathological Society of Great Britain and Ireland.
Deep learning based on hematoxylin–eosin staining outperforms immunohistochemistry in predicting molecular subtypes of gastric adenocarcinoma
Authors: Flinner Nadine , Gretser Steffen , Quaas Alexander , Bankov Katrin , Stoll Alexandra K , Heckmann Lara E , Mayer Robin S , Doering Claudia , Demes Melanie C , Buettner Reinhard , Rueschoff Josef , Wild Peter J
Published: February 2022

In gastric cancer (GC), there are four molecular subclasses that indicate whether patients respond to chemotherapy or immunotherapy, according to the TCGA. In clinical practice, however, not every patient undergoes molecular testing. Many laboratories have used well‐implemented in situ techniques (IHC and EBER‐ISH) to determine the subclasses in their cohorts. Although multiple stains are used, we show that a staining approach is unable to correctly discriminate all subclasses. As an alternative, we trained an ensemble convolutional neuronal network using bagging that can predict the molecular subclass directly from hematoxylin–eosin histology. We also identified patients with predicted intra‐tumoral heterogeneity or with features from multiple subclasses, which challenges the postulated TCGA‐based decision tree for GC subtyping. In the future, deep learning may enable targeted testing for molecular subtypes and targeted therapy for a broader group of GC patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Chitosan‐capped silver nanoparticles: A comprehensive study of polymer molecular weight effect on the reaction kinetic, physicochemical properties, and synergetic antibacterial potential
Authors: Kulikouskaya Viktoryia , Hileuskaya Kseniya , Kraskouski Aliaksandr , Kozerozhets Irina , Stepanova Elena , Kuzminski Ivan , You Lijun , Agabekov Vladimir
Published: February 2022

The search for novel efficient antibacterial agents is attracting a great attention due to the unregulated use of common antibiotics and development of multidrug‐resistant bacteria strains. This paper proposes an eco‐friendly approach to obtain stable chitosan‐capped silver nanoparticles with controlled physicochemical and biological properties using reducing and stabilizing capacity of chitosan. The study of the influence of chitosan characteristics on the kinetic of Ag+ reduction showed that an increase in polysaccharide molecular weight led to a decrease in their reducing ability. The synthesized silver nanoparticles were characterized by UV and FTIR spectroscopy, TEM, XRD, DLS. The relationships between physicochemical characteristics of the formed silver nanoparticles and the type of used chitosan, as well as synthesis temperature, were determined. It has been demonstrated that spherically‐shaped (13–27 nm) and positively‐charged (zeta‐potential 26.1–29.5 mV) silver nanoparticles with a single symmetric SPR band at 408–418 nm are stable during 6 months in a colloidal form, and can be produced with the assistance of low‐molecular weight chitosan (20–30 kDa) at 95°C. The synthesized silver nanoparticles enhanced the antibacterial activity of kanamycin and ampicillin against both gram‐negative and gram‐positive bacteria. These results revealed the prospects for the application of chitosan‐capped silver nanoparticles to create new effective antibacterial systems (gels, films, etc).
Modified Burgers‐Reimschuessel model for moisture‐sensitive polymers
Authors: Chen Yu , Ayranci Cagri , Tang Tian
Published: February 2022

Viscoelastic properties of moisture‐sensitive polymers can be significantly affected by moisture in the ambient environment, resulting in drastic changes in the properties as the absorbed moisture content increases. In this article, a simple yet important modification to the Reimschuessel model is introduced by considering both plasticization and anti‐plasticization induced by water molecules. The proposed model is validated against the results of four different polymers obtained by Onogi et al., which demonstrates its capability of describing the available data. This model can be used to estimate the performance and service life of products produced using moisture‐sensitive polymers. It also reveals that small amounts of diffused moisture might have a stiffening effect on the mechanical properties of hydrophilic polymers.
Targeting protein tyrosine phosphatase 1B in obesity‐associated colon cancer: Possible role of sweet potato (Ipomoea batatas)
Authors: Sain Arindam , Khamrai Dipshikha , Kandasamy Thirukumaran , Naskar Debdut
Published: February 2022

Protein tyrosine phosphatase 1B (PTP1B) has emerged as one of the links between obesity and colon cancer (CC). Anti‐obesity and anti‐CC attributes of sweet potato (Ipomoea batatas) reported sparsely. Here, we aimed to study the potential of PTP1B as a target in CC, particularly in obese population. Expression and genomic alteration frequency of PTPN1 (PTP1B) were checked in CC. Interacting partners of PTP1B through STRING and hub genes through Cytoscape (MCODE) were identified. Hub genes were subjected to functional enrichment analyses (via Metascape), differential gene expression, copy number variation, and single nucleotide variation analyses (GSCA database). Cancer‐related pathways and associated immune infiltrates of the hub genes were checked too. Eleven sweet potato‐derived compounds selected through drug likeness (DL) and toxicity filters were explored via molecular docking (AutoDock Vina) to reveal the interactions with PTP1B. Genomic alteration frequency of the PTPN1 was highest in CC compared to all the other TCGA cancers, and a high expression (RNA and protein) is also observed in CC that correlated well to a poor overall survival (OS). Furthermore, PTP1B and related proteins were enriched in different biological processes and signaling pathways related to carcinogenesis including epithelial–mesenchymal transition. Overall, PTP1B identified as a potential target in obesity‐linked CC and sweet potato might exert its protective action by targeting the PTP1B. Sweet potato compounds (e.g., pelargonidin and luteolin) interacted with the catalytic P loop and the WPD loop of the PTP1B. Furthermore, MD simulation study ascertained that luteolin has the highest affinity against the PTP1B, whereas pelargonidin and quercetin showed good binding affinity too, thus can be explored further.
Design, synthesis, and insecticidal and fungicidal activities of quaternary ammonium salt derivatives of a triazolyphenyl isoxazoline insecticide
Authors: Huang Shi‐sheng , Zhu Bin‐bing , Wang Kai‐hua , Yu Mo , Wang Zi‐wen , Li Yongqiang , Liu Yu‐xiu , Zhang Peng‐li , Li Shou‐jun , Li Ya‐ling , Liu Ai‐ling , Wang Qing‐min
Published: February 2022

BACKGROUND

Insect pests seriously decrease the yield and quality of agricultural crops. Resistance to commonly used insecticides is increasingly undermining their effectiveness, and therefore the development of agents with novel modes of action is desirable. Isoxazolines are a new class of insecticides that act on γ‐aminobutyric acid (GABA) gated chloride channels. In this work, we used the highly active 4‐triazolyphenyl isoxazoline DP‐9 as a parent structure to design and synthesize a series of quaternary ammonium salt (QAS) derivatives, and we systematically evaluated their insecticidal and antifungal activities.

RESULTS

Many of the synthesized QASs exhibit insecticidal activities equivalent to or higher than that of DP‐9. In particular, compounds I‐31 (93%, 0.00005 mg/L) and I‐34 (80%, 0.00001 mg/L) showed insecticidal activities against diamondback moth larvae that were 2–10 times higher than those of fluralaner (70%, 0.0001 mg/L) and DP‐9 (80%, 0.0001 mg/L), in addition to showing excellent activities against oriental armyworm, fall armyworm, cotton bollworm, corn borer, and mosquito larvae. Furthermore, all of the synthesized compounds also showed broad‐spectrum fungicidal activities.

CONCLUSION

The insecticidal activities of QAS derivatives of DP‐9 were the same as or better than the activity of DP‐9. Compounds I‐31 and I‐34 showed better insecticidal activities against diamondback moth larvae than fluralaner and DP‐9, and thus are promising new candidates for insecticide research.
Depthgram: Visualizing outliers in high‐dimensional functional data with application to fMRI data exploration
Authors: Alemán‐Gómez Yasser , Arribas‐Gil Ana , Desco Manuel , Elías Antonio , Romo Juan
Published: February 2022

Functional magnetic resonance imaging (fMRI) is a non‐invasive technique that facilitates the study of brain activity by measuring changes in blood flow. Brain activity signals can be recorded during the alternate performance of given tasks, that is, task fMRI (tfMRI), or during resting‐state, that is, resting‐state fMRI (rsfMRI), as a measure of baseline brain activity. This contributes to the understanding of how the human brain is organized in functionally distinct subdivisions. fMRI experiments from high‐resolution scans provide hundred of thousands of longitudinal signals for each individual, corresponding to brain activity measurements over each voxel of the brain along the duration of the experiment. In this context, we propose novel visualization techniques for high‐dimensional functional data relying on depth‐based notions that enable computationally efficient 2‐dim representations of fMRI data, which elucidate sample composition, outlier presence, and individual variability. We believe that this previous step is crucial to any inferential approach willing to identify neuroscientific patterns across individuals, tasks, and brain regions. We present the proposed technique via an extensive simulation study, and demonstrate its application on a motor and language tfMRI experiment.
Morphological and Transcriptional Evaluation of Multiple Facial Cutaneous Hyperpigmented Spots
Authors: Hakozaki T. , Jarrold B. , Zhao W. , Laughlin T. , Whittenbarger D. , Jewell-Motz E. A. , Boissy R. E.
Published: February 2022

Background

Morphological characteristics of major facial hyperpigmented spots have been well documented. However, detailed alterations of respective transcriptional profile for each spot and in-depth comparisons across multiple spot types have not been reported.

Objectives

To comprehensively assess and compare multiple facial hyperpigmented spot types at the morphological and molecular levels by utilising transcriptional expression profiling with correlation to quantified histological features.

Methods

Multiple types of facial spot biopsies were collected from Chinese women and compared to additional biopsies taken from adjacent healthy skin. The types of spots included Solar Lentigos with both elongated dermal-epidermal junction (DEJ) (SL[E]) and flat DEJ (SL[F]), Seborrhoeic Keratosis (SK), Melasma, Freckles, Post-inflammatory hyperpigmentation of resolving acne (PIH[A]) and other stimuli (PIH[O]). Combined histomorphometry, immunohistology, and transcriptome analysis for suprabasal-epidermis, basal-epidermis, and dermal compartments dissected by Laser Capture Microdissection (LCM) were conducted and compared across different spot types.

Results

Each spot type was confirmed to have the unique histological pathology already documented elsewhere. Most of the spot types except Melasma and PIH (A) revealed similar melanocyte density to adjacent skin. All spots exhibited increased melanin synthesis, melanosome transportation, as well as enhanced melanocyte dendricity, however, each spot revealed a distinct transcriptome regulation pattern in pigmentation pathways. Upregulation of pigmentation genes was also observed in the dermis of SL(F), SL(E), SK and PIH(O), associated with significant modulation of DEJ related genes in basal-epidermis and/or dermal compartments, suggesting potential melanocyte infiltration into the dermis due to impaired DEJ quality. Beyond upregulated pigmentation, for most spots, gene expression in the suprabasal-epidermis regulating keratinisation was significantly upregulated in conjunction with thickened stratum corneum. Furthermore, downregulation of tight junction related genes represented by claudin-1 was observed in majority of spot types, suggesting compromised barrier function could be a similarity across spots. Additionally, Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) was upregulated in all types of spots, indicating involvement of cell senescence as a common theme.

Conclusion

This comprehensive and comparative study based on the histological and transcriptional analysis of three skin compartments provided unique insights into specific causations as well as differences and similarities across multiple hyperpigmented spot types.
Photopolymerized Features via Beam Pen Lithography as a Novel Tool for the Generation of Large Area Protein Micropatterns
Authors: Zhang Xinpeng , Ding Shaowei , Magoline Jared , Ivankin Andrey , Mirkin Chad A.
Published: February 2022

A cantilever‐free scanning probe lithography (CF‐SPL)‐based method for the rapid polymerization of nanoscale features on a surface via crosslinking and thiol‐acrylate photoreactions is described, wherein the nanoscale position, height, and diameter of each feature can be finely and independently tuned. With precise spatiotemporal control over the illumination pattern, beam pen lithography (BPL) allows for the photo‐crosslinking of polymers into ultrahigh resolution features over centimeter‐scale areas using massively parallel >160 000 pen arrays of individually addressable pens that guide and focus light onto the surface with sub‐diffraction resolution. The photoinduced crosslinking reaction of the ink material, which is composed of photoinitiator, diphenyl(2,4,6‐trimethylbenzoyl) phosphine oxide, poly(ethylene glycol) diacrylate, and thiol‐modified functional binding molecules (i.e., thiol‐PEG‐biotin or 16‐mercaptohexanoic acid), proceeds to ≈80% conversion with UV exposure (72 mW cm−2) for short time periods (0.5 s). Such polymer patterns are further reacted with proteins (streptavidin and fibronectin) to yield protein arrays with feature arrangements at high resolution and densities controlled by local UV exposure. This platform, which combines polymer photochemistry and massive arrays of scanning probes, constitutes a new approach to making biomolecular microarrays in a high‐throughput and high‐yielding manner, opening new routes for biochip synthesis, bioscreening, and cell biology research.
Sacrificial W Facilitates Self‐Reconstruction with Abundant Active Sites for Water Oxidation
Authors: Fan Ke , Zou Haiyuan , Ding Yunxuan , Dharanipragada N. V. R. Aditya , Fan Lizhou , Inge A. Ken , Duan Lele , Zhang Biaobiao , Sun Licheng
Published: February 2022

Water oxidation is an important reaction for multiple renewable energy conversion and storage‐related devices and technologies. High‐performance and stable electrocatalysts for the oxygen evolution reaction (OER) are urgently required. Bimetallic (oxy)hydroxides have been widely used in alkaline OER as electrocatalysts, but their activity is still not satisfactory due to insufficient active sites. In this research, A unique and efficient approach of sacrificial W to prepare CoFe (oxy)hydroxides with abundant active species for OER is presented. Multiple ex situ and operando/in situ characterizations have validated the self‐reconstruction of the as‐prepared CoFeW sulfides to CoFe (oxy)hydroxides in alkaline OER with synchronous W etching. Experiments and theoretical calculations show that the sacrificial W in this process induces metal cation vacancies, which facilitates the in situ transformation of the intermediate metal hydroxide to CoFe‐OOH with more high‐valence Co(III), thus creating abundant active species for OER. The Co(III)‐rich environment endows the in situ formed CoFe oxyhydroxide with high catalytic activity for OER on a simple flat glassy carbon electrode, outperforming those not treated by the sacrificial W procedure. This research demonstrates the influence of etching W on the electrocatalytic performance, and provides a low‐cost means to improve the active sites of the in situ self‐reconstructed bimetallic oxyhydroxides for OER.
Programmable DNA Hydrogels as Artificial Extracellular Matrix
Authors: Wei Yuhan , Wang Kaizhe , Luo Shihua , Li Fan , Zuo Xiaolei , Fan Chunhai , Li Qian
Published: February 2022

The cell microenvironment plays a crucial role in regulating cell behavior and fate in physiological and pathological processes. As the fundamental component of the cell microenvironment, extracellular matrix (ECM) typically possesses complex ordered structures and provides essential physical and chemical cues to the cells. Hydrogels have attracted much attention in recapitulating the ECM. Compared to natural and synthetic polymer hydrogels, DNA hydrogels have unique programmable capability, which endows the material precise structural customization and tunable properties. This review focuses on recent advances in programmable DNA hydrogels as artificial extracellular matrix, particularly the pure DNA hydrogels. It introduces the classification, design, and assembly of DNA hydrogels, and then summarizes the state‐of‐the‐art achievements in cell encapsulation, cell culture, and tissue engineering with DNA hydrogels. Ultimately, the challenges and prospects for cellular applications of DNA hydrogels are delivered.
SABDM: A self‐attention based bidirectional‐RNN deep model for requirements classification
Authors: Kaur Kamaljit , Kaur Parminder
Published: February 2022

The success of software depends upon functional and non‐functional requirements as both requirements are equally important in software development. However, the requirements engineering community still lacks in comprehensive understanding of functional and non‐functional requirements. In addition, the requirements in software documents are expressed in natural language and also intertwined with each other. Requirements classification is a crucial task that correctly extracts functional and non‐functional requirements and organizes them in specified categories. Automated classification of software requirements leads to reduced ambiguity, misunderstanding, and development cost. Most of the recent studies have used machine learning and deep learning techniques for automatic classification of requirements. However, there is one drawback of such techniques, that is, poor generalization. To address these problems, this research work proposes self‐attention based bidirectional LSTM deep model. This automated approach has used recurrent neural network, which handle long sequential natural language requirements statements and classify them into five classes such as capability, maintainability, performance, security, and usability. The proposed approach train and evaluate over pre‐labeled dataset comprised of 34 industrial requirements specifications and PROMISE dataset. Over this dataset, the proposed approach yields 95% of precision, 96% of recall, 96% of F‐measure, and 96% of accuracy. The proposed approach can be applied to wide variety of datasets with different domain. Furthermore, this paper applies pre‐processing techniques to improve the performance of the requirements classification model. The results of the proposed model are compared with existing baseline state‐of‐art techniques, and it is shown that the proposed model outperforms the baseline models in requirements classification.
Investigating the Effect of Selected Ultraviolet Light Emitting Diode Treatments on the Inactivation of B. subtilis, the Pasting Properties and the Surface Morphology of Tapioca Starch
Authors: Hinds Laura M. , Tiwari Brijesh K. , O'Donnell Colm P.
Published: February 2022

This study investigates various ultraviolet light emitting diode (UV LED) treatments on the microbial load, pasting profile, and surface morphology of tapioca starch. Tapioca starch samples are subjected to various UV LED treatments employing different wavelengths (280, 300, and 365 nm) and treatment durations (5, 10, and 20 min). For microbiological analysis tapioca starch samples are inoculated with Bacillus subtilis and subjected to treatment. Furthermore, food quality parameters are also investigated by assessing the impact of all UV LED treatments on the pasting profile using rapid visco analysis and the surface morphology using scanning electron microscopy. Significant reductions are achieved for UV LED treatments after 20 min with 300 and 365 nm showing reductions to 4.03 ± 1.55 log10 and 6.52 ± 0.31 log10 cfu g–1, respectively, from 7.53 ± 0.11 log10 cfu g–1. For food quality assessments, no significant changes in pasting properties or surface morphology are observed for any treatment investigated. This study highlights the potential of this technology as a decontamination tool in the food industry.
Morphological, Thermal, and Rheological Properties of Starch from Brown Rice and Germinated Brown Rice from Different Cultivars
Authors: Pal Priyanka , Kaur Parmeet , Singh Narpinder , Kaur Amritpal , Inouchi Naoyoshi , Kubota Yuka
Published: February 2022

Morphological, thermal, functional, pasting, and rheological properties of starch from BR (Brown rice) and GBR (Germinated brown rice) (PB1, PS44, PB1509, PB1121, PS5) are investigated. Scanning electron microscopy shows the presence of rougher and slightly eroded pits starch granules after germination. Starch from both the BR and GBR has the highest proportion of granules of 5–10 µm size and the lowest of 20–60 µm size. Starch from GBR shows lower gelatinization temperatures and enthalpy of gelatinization. GBR starch has a higher amount of long side chains and lower short side chains of amylopectin as compared to BR starch. Starches from BR show higher moduli as compared to their counterpart starches from GBR. GBR starch from different rice cultivars shows different amylopectin molecular structures, crystallinity, and thermal properties than BR starch. The lower paste viscosities and transition temperatures of GBR starch make it more suitable for the formulation of food products where a higher amount of starch is required without a rise in viscosity.