bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating CD8+ mucosal‐associated invariant T cells correlate with improved treatment responses and overall survival in anti‐PD‐1‐treated melanoma patients
Authors: Vorwald Victoria M , Davis Dana M , Van Gulick Robert J , Torphy Robert J , Borgers Jessica SW , Klarquist Jared , Couts Kasey L , Amato Carol M , Cogswell Dasha T , Fujita Mayumi , Castleman Moriah J , Davis Timothy , Lozupone Catherine , Medina Theresa M , Robinson William A , Gapin Laurent , McCarter Martin D , Tobin Richard P
Published: January 2022

Objectives

While much of the research concerning factors associated with responses to immune checkpoint inhibitors (ICIs) has focussed on the contributions of conventional peptide‐specific T cells, the role of unconventional T cells, such as mucosal‐associated invariant T (MAIT) cells, in human melanoma remains largely unknown. MAIT cells are an abundant population of innate‐like T cells expressing a semi‐invariant T‐cell receptor restricted to the MHC class I‐like molecule, MR1, presenting vitamin B metabolites derived from bacteria. We sought to characterise MAIT cells in melanoma patients and determined their association with treatment responses and clinical outcomes.

Methods

In this prospective clinical study, we analysed the frequency and functional profile of circulating and tumor‐infiltrating MAIT cells in human melanoma patients. Using flow cytometry, we compared these across metastatic sites and between ICI responders vs. non‐responders as well as healthy donors.

Results

We identified tumor‐infiltrating MAIT cells in melanomas across metastatic sites and found that the number of circulating MAIT cells is reduced in melanoma patients compared to healthy donors. However, circulating MAIT cell frequencies are restored by ICI treatment in responding patients, correlating with treatment responses, in which patients with high frequencies of MAIT cells exhibited significantly improved overall survival.

Conclusion

Our results suggest that MAIT cells may be a potential predictive marker of responses to immunotherapies and provide rationale for testing MAIT cell‐directed therapies in combination with current and next‐generation ICIs.
Origin, molecular specification, and stemness of astrocytes
Authors: Zheng Kang , Huang Hao , Yang Junlin , Qiu Mengsheng
Published: January 2022

Astrocytes are the most abundant cell type in the central nervous system, carrying out a wide spectrum of biological functions. During early development, neural progenitor cells in the ventricular zone first produce neurons, followed by macroglia in the form of astrocytes or oligodendrocytes. Although the lineage progression of oligodendrocytes has been well understood, the developmental staging of astrocytes has not been defined and the molecular mechanisms underlying their fate specification and differentiation remain largely unknown. The recent advent of sophisticated molecular biology technology, especially single‐cell sequencing, has enabled a deeper understanding of the patterning and molecular specification of astrocyte lineage. Based on the recent single‐cell sequencing data, we provide an up‐to‐date and mechanistic review of the early development and heterogeneity of astrocyte lineage in the developing cortex, and compile a list of stage‐specific markers for astrocyte development. In addition, emerging evidence suggests that under physiological conditions, mature astrocytes are partially specialized progenitor cells that have functionally adapted to local neuronal microenvironment. Under pathological or injury conditions, astrocytes are capable of reentering cell cycles and differentiating into other neural cell types under the influence of both intrinsic factors and environmental cues.
From a non‐targeted metabolomics approach to a targeted biomarkers strategy to highlight testosterone abuse in equine. Illustration of a methodological transfer between platforms and laboratories
Authors: Cloteau Chloé , Dervilly Gaud , Kaabia Zied , Bagilet Florian , Delcourt Vivian , Loup Benoit , Guitton Yann , Royer Anne‐Lise , Monteau Fabrice , Garcia Patrice , Popot Marie‐Agnès , Le Bizec Bruno , Bailly‐Chouriberry Ludovic
Published: January 2022

In order to overcome the challenge associated with the screening of Anabolic‐Androgenic Steroids abuses in animal competitions, a non‐targeted liquid chromatography coupled to high resolution mass spectrometry based metabolomics approach was implemented on equine urine samples to highlight potential biomarkers associated with the administration of such compounds, using testosterone esters as model steroids. A statistical model relying on four potential biomarkers intensity could be defined to predict the status of the samples. With a routine application perspective, the monitoring of the highlighted potential biomarkers was first transferred into high‐throughput liquid chromatography‐selected reaction monitoring (LC‐SRM). The model's performances and robustness of the approach were preserved and providing a first demonstration of metabolomics‐based biomarkers integration within a targeted workflow using common benchtop MS instrumentation. In addition, with a view to the widespread implementation of such biomarker‐based tools, we have transferred the method to a second laboratory with similar instrumentation. This proof of concept allows the development and application of biomarker‐based strategies to meet current doping control needs.
The novel proteomic signature for cardiac allograft vasculopathy
Authors: Wei Dongmei , Trenson Sander , Van Keer Jan M. , Melgarejo Jesus , Cutsforth Ella , Thijs Lutgarde , He Tianlin , Latosinska Agnieszka , Ciarka Agnieszka , Vanassche Thomas , Van Aelst Lucas , Janssens Stefan , Van Cleemput Johan , Mischak Harald , Staessen Jan A. , Verhamme Peter , Zhang Zhen‐Yu
Published: January 2022

Aims

Cardiac allograft vasculopathy (CAV) is the major long‐term complication after heart transplantation, leading to mortality and re‐transplantation. As available non‐invasive biomarkers are scarce for CAV screening, we aimed to identify a proteomic signature for CAV.

Methods and results

We measured urinary proteome by capillary electrophoresis coupled with mass spectrometry in 217 heart transplantation recipients (mean age: 55.0 ± 14.4 years; women: 23.5%), including 76 (35.0%) patients with CAV diagnosed by coronary angiography. We randomly and evenly grouped participants into the derivation cohort (n = 108, mean age: 56.4 ± 13.8 years; women: 22.2%; CAV: n = 38) and the validation cohort (n = 109, mean age: 56.4 ± 13.8 years; women: 24.8%, CAV: n = 38), stratified by CAV. Using the decision tree‐based machine learning methods (extreme gradient boost), we constructed a proteomic signature for CAV discrimination in the derivation cohort and verified its performance in the validation cohort. The proteomic signature that consisted of 27 peptides yielded areas under the curve of 0.83 [95% confidence interval (CI): 0.75–0.91, P < 0.001] and 0.71 (95% CI: 0.60–0.81, P = 0.001) for CAV discrimination in the derivation and validation cohort, respectively. With the optimized threshold of 0.484, the sensitivity, specificity, and accuracy for CAV differentiation in the validation cohort were 68.4%, 73.2%, and 71.6%, respectively. With adjustment of potential clinical confounders, the signature was significantly associated with CAV [adjusted odds ratio: 1.31 (95% CI: 1.07–1.64) for per 0.1% increment in the predicted probability, P = 0.012]. Diagnostic accuracy significantly improved by adding the signature to the logistic model that already included multiple clinical risk factors, suggested by the integrated discrimination improvement of 9.1% (95% CI: 2.5–15.3, P = 0.005) and net reclassification improvement of 83.3% (95% CI: 46.7–119.5, P < 0.001). Of the 27 peptides, the majority were the fragments of collagen I (44.4%), collagen III (18.5%), collagen II (3.7%), collagen XI (3.7%), mucin‐1 (3.7%), xylosyltransferase 1 (3.7%), and protocadherin‐12 (3.7%). Pathway analysis performed in Reactome Pathway Database revealed that the multiple pathways involved by the signature were related to the pathogenesis of CAV, such as collagen turnover, platelet aggregation and coagulation, cell adhesion, and motility.

Conclusions

This pilot study identified and validated a urinary proteomic signature that provided a potential approach for the surveillance of CAV. These proteins might provide insights into CAV pathological processes and call for further investigation into personalized treatment targets.
Nafion® Coated Electropolymerised Flavanone‐based pH Sensor
Authors: Miranda Monica , Carvetta Clara , Sisodia Neel , Shirley Luke , Day Cristina D. , McGuinness Kay L. , Wadhawan Jay D. , Lawrence Nathan S.
Published: January 2022

This work summarizes the electrochemical response of flavanone carbon composite electrodes in comparison with Nafion®‐coated flavanone carbon composite electrodes, for use as voltammetric pH sensors in both buffered and low‐buffered media. Square wave voltammetric measurements suggest the peak potential achieved from the electrochemical polymerization after the electron‐proton oxidation responds with accuracy to buffered pH solutions for both coated and non‐coated electrodes, with a potential shift of 55.1 mV and 54.6 mV per pH unit respectively. However, a considerable improvement in stability, accuracy and sensitivity is provided by the proton‐transfer Nafion® layer in CO2 bubbled sea water. Furthermore, Nafion®‐coated flavanone carbon composite electrodes predicted a pH of 8.04 for the commercial seawater, which is in excellent agreement with the measured pH 8.05 value.
Adverse childhood experiences among a treatment‐seeking sample of adults with eating disorders
Authors: Rienecke Renee D. , Johnson Craig , Mehler Philip S. , Le Grange Daniel , Manwaring Jamie , Duffy Alan , McClanahan Susan , Blalock Dan V.
Published: January 2022

Objective

The purpose of the current study was to examine the prevalence of adverse childhood experiences (ACEs) among adults with eating disorders (EDs), to assess whether experiencing a greater number of ACEs is associated with more severe ED psychopathology, and to determine whether ACEs predict treatment outcome.

Method

Participants were 1819 patients (88.5% female, ages 18–72) admitted to one of two treatment facilities at inpatient, residential, or partial hospitalisation levels of care. The Adverse Childhood Experiences Survey and the Eating Pathology Symptom Inventory (EPSI) were completed at admission and the EPSI at discharge.

Results

Female patients reported higher ACEs than males (p = 0.03), and all diagnoses except avoidant/restrictive food intake disorder had significantly higher ACEs than patients with anorexia nervosa‐restricting type (AN‐R) (p's < 0.01). Across diagnoses, higher ACEs were associated with decreases in binge eating scores during treatment, but were not associated with changes in purging or restricting. Within diagnoses, higher ACEs scores were associated with decreases in purging for patients with AN‐R and increases in purging for patients with binge eating disorder.

Conclusions

Results partially supported the hypothesis that higher ACEs would be associated with more severe ED psychopathology.
Phenolic profile and antioxidant activity of free/bound phenolic compounds of sesame and properties of encapsulated nanoparticles in different wall materials
Authors: Esmaeilzadeh Kenari Reza , Razavi Razie
Published: January 2022

This study aimed to evaluate the antioxidant activity of free and bound flavonoid or phenolic compounds extracted from the sesame seed (Oltan and Yekta varieties) as natural antioxidants and to demonstrate the properties of nanoparticles. The total phenolic content (TPC) of Oltan was higher (864.70 mg GAE/100 g seed) than that of Yekta (629.23 mg GAE/100 g seed). Oltan took up higher amounts of free (516.86 mg GAE/100 g seed) and bound (347.83 mg GAE/100 g seed) phenolics than Yekta. Also, the Yekta variety exhibited lower amounts of free (45.89 mg CE/100 g seed) and bound flavonoids (21.51 mg CE/100 g seed) and the total flavonoid content (TFC) (67.40 mg CE/100 g seed). Chlorogenic acid was the major phenolic compound present in the sesame seed. In both the DPPH and ferric reducing antioxidant power (FRAP) assays, the highest antioxidant activity was observed in the Oltan variety. Free phenolics showed the highest antioxidant activity, followed by bound phenolics, free and bound flavonoids. Therefore, free phenolics of the Oltan variety were encapsulated in Portulaca oleracea and Trigonella foenum‐graecum seed gums. All nanoparticles showed nanometric size from 236.1 to 680.7 nm, negative zeta potential from −35.4 to −18.3 mV, high encapsulation efficiency from 61.35% to 74.49%, and desirable polydispersity index (PDI) between 0.315 and 0.332. Higher release of phenolics and sedimentation rate were observed in phenolic compounds encapsulated in Khorfeh and Shanbalileh, respectively. The gradual release of phenolic compounds, as well as sedimentation rate of composite coating during 40 days of storage, demonstrated that nanoencapsulated phenolics of sesame within the composite gum coating could be used as natural antioxidants in food systems.
Inhibition of histamine accumulation by novel histamine‐degrading species of Staphylococcus sp. isolated from goats and sheep milk
Authors: Pashangeh Safoora , Shekarforoush Seyed Shahram , Aminlari Mahmoud , Hosseinzadeh Saeid , Nizet Victor , Dahesh Samira , Rahmdel Samane
Published: January 2022

Histamine is an active amine compound that occurs in various fermented foods that may cause adverse effects on the human health. Certain microorganisms are able to degrade histamine by an oxidative deamination reaction. Therefore, the present study aimed to quantify histamine‐forming and/or ‐degrading activity of the isolates derived from milk of goat and sheep herds, in Iran, by the capillary zone electrophoresis (CZE) method; and we evaluated the molecular characteristics of staphylococcal isolates. Among 243 staphylococcal isolates, 29 histamine‐degrading bacteria were identified. One of these isolates, identified as Staph. epidermidis, No. 605, exhibited the highest activity compared to others, degrading available histamine to 58.33% within 24 h. By polymerase chain reaction (PCR) analysis, the isolate, No. 605 that exhibited remarkable histamine‐degrading activity lacked the genes encoding coagulase and DNase, nor did it harbor any of the five classical enterotoxin genes. This is the first report to show that seven Staphylococcus species, including Staph. chromogenes, Staph. aureus, Staph. haemolyticus, Staph. epidermidis, Staph. pseudintermedius, Staph. agnetis, and Staph. hyicus, were able to degrade histamine, which were hitherto not known to have this capacity. Therefore, histamine‐degrading activity is a definite criterion to introduce fermenting organisms able to decrease histamine content in different food products.
Prenatal air pollution exposure and neonatal health
Authors: Palma Alessandro , Petrunyk Inna , Vuri Daniela
Published: January 2022

Air pollution has been shown to have adverse effects on many health outcomes including respiratory effects, cardiovascular effects, and mortality. However, evidence on the effects of prenatal exposure is still limited. We investigate the causal impact of prenatal exposure to air pollution on neonatal health in Italy in the 2000s. We exploit variation in rainfall shocks to instrument for non‐random air pollution exposure. Our empirical setting combines detailed information on mother's residential location from birth certificates with PM10 concentrations from air pollution monitors. Ten additional units in the average PM10 level (approximately one standard deviation) would decrease birth weight by about 0.5% and gestational age by 0.16%; it would increase the prevalence of low birth weight by 22% and of preterm birth by 16%. The effects are stronger in magnitude for third trimester exposure and for less educated mothers. These findings suggest that the health impacts of air pollution on newborns are unequally distributed in the population.
Notch‐triggered maladaptation of liver sinusoidal endothelium aggravates nonalcoholic steatohepatitis through endothelial nitric oxide synthase
Authors: Fang Zhi‐Qiang , Ruan Bai , Liu Jing‐Jing , Duan Juan‐Li , Yue Zhen‐Sheng , Song Ping , Xu Hao , Ding Jian , Xu Chen , Dou Guo‐Rui , Wang Lin
Published: January 2022

Background and Aims

Although NASH can lead to severe clinical consequences, including cirrhosis and hepatocellular carcinoma, no effective treatment is currently available for this disease. Increasing evidence indicates that LSECs play a critical role in NASH pathogenesis; however, the mechanisms involved in LSEC‐mediated NASH remain to be fully elucidated.

Approach and Results

In the current study, we found that LSEC homeostasis was disrupted and LSEC‐specific gene profiles were altered in methionine–choline‐deficient (MCD) diet‐induced NASH mouse models. Importantly, Notch signaling was found to be activated in LSECs of NASH mice. To then investigate the role of endothelial Notch in NASH progression, we generated mouse lines with endothelial‐specific Notch intracellular domain (NICD) overexpression or RBP‐J knockout to respectively activate or inhibit Notch signaling in endothelial cells. Notably, endothelial‐specific overexpression of the NICD accelerated LSEC maladaptation and aggravated NASH, whereas endothelial cell–specific inhibition of Notch signaling restored LSEC homeostasis and improved NASH phenotypes. Furthermore, we demonstrated that endothelial‐specific Notch activation exacerbated NASH by inhibiting endothelial nitric oxide synthase (eNOS) transcription, whereas administration of the pharmacological eNOS activator YC‐1 alleviated hepatic steatosis and lipid accumulation resulting from Notch activation. Finally, to explore the therapeutic potential of using Notch inhibitors in NASH treatment, we applied two gamma‐secretase inhibitors—DAPT and LY3039478—in an MCD diet‐induced mouse model of NASH, and found that both inhibitors effectively ameliorated hepatic steatosis, inflammation, and liver fibrosis.

Conclusions

Endothelial‐specific Notch activation triggered LSEC maladaptation and exacerbated NASH phenotypes in an eNOS‐dependent manner. Genetic and pharmacological inhibition of Notch signaling effectively restored LSEC homeostasis and ameliorated NASH progression.
Numerical simulation of MHD mixed convection flow of Al2O3–water nanofluid over two hot obstacles
Authors: Hosseini Abadshapoori M. , Saidi M. H.
Published: January 2022

The problem of cooling two hot blocks in a novel geometry using magnetohydrodynamic flow of Al2O3–water nanofluid has been studied utilizing a D2Q9 Lattice Boltzmann Model. While the Hartmann number (Ha) takes 0, 50, or 100 values, the Richardson number (Ri) varies between 0.02 and 20. Four variations of the geometry are selected. The gravity angle is set to be either , , or . Results reveal that the Nusselt number (Nu) increases as Ri increases for all cases. Furthermore, the Hartmann number has a deteriorating effect on the Nusselt number except for low Ri numbers. In addition, the results indicate that while the geometrical configuration is having a considerable impact on the average Nusselt number at low and high Richardson numbers, it has a negligible effect at the mixed convection flow. The best angle for the gravitational force is also between 0 and . A new correlation for the Nu number based on all parameters is also presented.
Simulated event‐scale flow and sediment generation responses to agricultural land cover change in lowland UK catchments
Authors: Escobar‐Ruiz Veronica , Smith Hugh G. , Macdonald Neil , Peñuela Andres
Published: January 2022

Agricultural land use can increase runoff and erosion leading to detrimental downstream impacts. This paper examines the impact of agricultural land cover change on runoff and sediment generation at event scales using a model‐based approach. SHETRAN, a physically based, spatially distributed model, was applied in two southwest England catchments to represent: (a) changes in the land cover (cropland extent and spatial arrangement), (b) changes in crop type and (c) use of riparian buffer strips. A total of 84 simulated events within a 4‐year period were used to quantify impacts on flow and sediment generation. We found past changes in land cover resulted in significant differences in sediment yield (p < 0.05). Linear regression showed an increase in flow and sediment yield proportional to increases in arable crop area (p < 0.001). The spatial arrangement of cropped fields and riparian buffer strips produced no significant differences in event flow or sediment yield (p > 0.05). However, buffer strip scenarios compared with the base run showed sediment load reductions for specific events, up to 20% and 15% for woodland and grass riparian buffers, respectively. When comparing crop types with and without the use of post‐harvest cover crops, we observed non‐significant differences for event flow and sediment yield. However, large reductions in modelled sediment yields occurred for some events (e.g., up to 60% for winter cereals, 50% for maize and 74% for spring cereals). For these scenarios, examination of rainfall event magnitude emphasized the importance of ground cover in mitigating soil erosion for maize and spring cereals, but not for winter cereals. Our findings indicate that significant changes in sediment delivery at the event scale over a multi‐year period are associated with variations in cropland extent and crop types, depending on rainfall magnitude, but not on the spatial arrangement of cropped fields or the use of riparian buffer strips.
Polymerizing small molecular acceptors for efficient all‐polymer solar cells
Authors: Kong Yuxin , Li Yuxiang , Yuan Jianyu , Ding Liming
Published: January 2022

All‐polymer solar cells (all‐PSCs) have received attention due to their morphological stability under thermal and mechanical stresses. Currently, the highest reported power conversion efficiency of all‐PSCs is over 17%, achieved by utilizing polymerized small molecular acceptors (PSMAs). However, the need for higher regiospecificity to avoid forming isomers during polymerization of SMAs still challenges the further applications of all‐PSCs. From this perspective, we focus on some recent studies and highlight the importance of controlling the regioregularity of PSMAs. In particular, integrating PSMAs with regioregularity endows the polymer acceptors with good absorption, superior backbone ordering, and optimal blend morphology compared with those obtained from regiorandom one. Moreover, the distinctive features that are derived from these regioregular PSMAs, such as the possibility of repeatable synthesis and reproducible device performance, herald a brighter future for scaling‐up and commercializing all‐PSCs. We expect this integrated strategy will inspire researchers to devote more efforts to further narrow the efficiency gap between the PSCs based on SMAs and PSMAs. Finally, we discuss the existing challenges and future prospects of PSMAs as new platform for further advancing all‐PSCs.
Reduction of PAPR in OTFS using normalized μ‐law and A‐law companding transform
Authors: Bitra Hanumantharao , Ponnusamy Palanisamy , Chintagunta Srinivasarao
Published: January 2022

In this letter, we propose a normalized ‐law and ‐law companding transform to reduce the peak‐to‐average power ratio (PAPR) of the orthogonal time‐frequency space (OTFS) signal. The normalized ‐law and ‐law transforms reduce the peak power while keeping the same average power before and after the companding transform, which leads to lowering the PAPR. This letter also presents a theoretical analysis of PAPR and transform gain for validating the companding transforms. Simulations demonstrate that the normalized ‐law obtains better PAPR reduction and BER performance than the normalized ‐law and exhibits superior BER performance than the existing ‐law transform.
Efficacy of the Developmental Trauma and Attachment Program in a residential setting
Authors: Lenz A. Stephen , Buckwalter Karen Doyle , Pester Danielle A. , Green Kelly , Reed Debbie
Published: January 2022

This evaluation inspected the degree of symptom improvement associated with the Developmental Trauma and Attachment Program for decreasing symptoms of posttraumatic stress disorder (PTSD) among youth in residential treatment following complex trauma scenarios associated with domestic and international adoption/foster care. Participants were 61 youth (Mage = 13.23 years) who were predominately born in the United States (n = 41) with 20 identifying with international domiciles. Results indicated statistically significant decreases in symptoms from admission to discharge associated with medium‐effect sizes across PTSD symptoms. Nearly one in three participants reported clinically significant changes associated with treatment, whereas two in five reported improvements but not in the clinically significant range. Female participants reported greater decreases in negative cognitions; however, no other differences in treatment response based on participant characteristics were detected. Limitations of the generalization of findings and recommendations for future researchers are provided.
Combined strategy of knowledge‐based rule selection and historical data percentile‐based range determination to improve an autoverification system for clinical chemistry test results
Authors: Zhu Jing , Wang Hao , Wang Beili , Hao Xiaoke , Cui Wei , Duan Yong , Zhang Yi , Ming Liang , Zhou Yingchun , Ding Haitao , Ou Hongling , Lin Weiwei , Lu Liu , Shang Yuanjiang , Yang Yong , Liang Xianming , Ma Jiangtao , Sun Wenhua , Chen Te , Han Guang , Han Meng , Yu Weiting , Pan Baishen , Guo Wei
Published: January 2022

Background

Current autoverification, which is only knowledge‐based, has low efficiency. Regular historical data analysis may improve autoverification range determination. We attempted to enhance autoverification by selecting autoverification rules by knowledge and ranges from historical data. This new system was compared with the original knowledge‐based system.

Methods

New types of rules, extreme values, and consistency checks were added and the autoverification workflow was rearranged to construct a framework. Criteria for creating rules for extreme value ranges, limit checks, consistency checks, and delta checks were determined by analyzing historical Zhongshan laboratory data. The new system's effectiveness was evaluated using pooled data from 20 centers. Efficiency improvement was assessed by a multicenter process.

Results

Effectiveness was evaluated by the true positive rate, true negative rate, and overall consistency rate, as compared to manual verification, which were 77.55%, 78.53%, and 78.3%, respectively for the new system. The original overall consistency rate was 56.2%. The new pass rates, indicating efficiency, were increased by 19%‒51% among hospitals. Further customization using individualized data increased this rate.

Conclusions

The improved system showed a comparable effectiveness and markedly increased efficiency. This transferable system could be further improved and popularized by utilizing historical data from each hospital.
A call for unity in DEIJ efforts using a proposed framework for Education, Recruitment, Retainment, Research, and Active outreach (ERA) for genetic counselors in the United States
Authors: Mercado Joanna , Lawrence Janette Z. , Moore Michelle , Neogi Arpita , Vig Hetal
Published: January 2022

Genetic counselors, like many other healthcare providers, play a vital role in genomic health care. As a profession, we, along with our colleagues and students, have recognized the need to improve and incorporate diversity, equity, inclusion, and justice (DEIJ) within our daily ways of practice to help create access to genomic technologies. In order to create systemic change and focus on unity, open communication, and transparency, we introduce a suggested framework called ERA (Education, Recruitment, Retainment, Research, and Active Outreach). This framework would benefit a genetic counselor throughout various stages of their career, from student to practicing genetic counselor, and can be broadly applied to all specialties of genomic medicine. Different iterations of DEIJ efforts have arisen in the National Society of Genetic Counselors (NSGC), from the D&I (Diversity and Inclusion) Task Force to the J.E.D.I (justice, equity, diversity, and inclusion) committee. The lack of recorded history of these previous efforts and the lack of communication between current DEIJ organizations is one of the many reasons the ERA framework demands unity and transparency to achieve sustainable positive change. Genetic counselors must unite and work collaboratively to conduct and promote DEIJ efforts, so the benefits of genomic medicine can be realized by all.
Risk scores for predicting HIV incidence among adult heterosexual populations in sub‐Saharan Africa: a systematic review and meta‐analysis
Authors: Jia Katherine M. , Eilerts Hallie , Edun Olanrewaju , Lam Kevin , Howes Adam , Thomas Matthew L. , Eaton Jeffrey W.
Published: January 2022

Introduction

Several HIV risk scores have been developed to identify individuals for prioritized HIV prevention in sub‐Saharan Africa. We systematically reviewed HIV risk scores to: (1) identify factors that consistently predicted incident HIV infection, (2) review inclusion of community‐level HIV risk in predictive models and (3) examine predictive performance.

Methods

We searched nine databases from inception until 15 February 2021 for studies developing and/or validating HIV risk scores among the heterosexual adult population in sub‐Saharan Africa. Studies not prospectively observing seroconversion or recruiting only key populations were excluded. Record screening, data extraction and critical appraisal were conducted in duplicate. We used random‐effects meta‐analysis to summarize hazard ratios and the area under the receiver‐operating characteristic curve (AUC‐ROC).

Results

From 1563 initial search records, we identified 14 risk scores in 13 studies. Seven studies were among sexually active women using contraceptives enrolled in randomized‐controlled trials, three among adolescent girls and young women (AGYW) and three among cohorts enrolling both men and women. Consistently identified HIV prognostic factors among women were younger age (pooled adjusted hazard ratio: 1.62 [95% confidence interval: 1.17, 2.23], compared to above 25), single/not cohabiting with primary partners (2.33 [1.73, 3.13]) and having sexually transmitted infections (STIs) at baseline (HSV‐2: 1.67 [1.34, 2.09]; curable STIs: 1.45 [1.17; 1.79]). Among AGYW, only STIs were consistently associated with higher incidence, but studies were limited (n = 3). Community‐level HIV prevalence or unsuppressed viral load strongly predicted incidence but was only considered in 3 of 11 multi‐site studies. The AUC‐ROC ranged from 0.56 to 0.79 on the model development sets. Only the VOICE score was externally validated by multiple studies, with pooled AUC‐ROC 0.626 [0.588, 0.663] (I2: 64.02%).

Conclusions

Younger age, non‐cohabiting and recent STIs were consistently identified as predicting future HIV infection. Both community HIV burden and individual factors should be considered to quantify HIV risk. However, HIV risk scores had only low‐to‐moderate discriminatory ability and uncertain generalizability, limiting their programmatic utility. Further evidence on the relative value of specific risk factors, studies populations not restricted to “at‐risk” individuals and data outside South Africa will improve the evidence base for risk differentiation in HIV prevention programmes.

PROSPERO Number

CRD42021236367
Omsk hemorrhagic fever virus is a tick‐borne encephalitis virus adapted to muskrat through host‐jumping
Authors: Kovalev Sergey Y. , Mazurina Elena A.
Published: January 2022

Omsk hemorrhagic fever was first described in the early 1940s and is a natural focal infection, spread exclusively in four regions of Western Siberia, and associated with muskrat (Ondatra zibethicus). The etiological agent of this disease is the Omsk hemorrhagic fever virus (OHFV) which is closely related to the tick‐borne encephalitis virus (TBEV), and its range entirely lies within the TBEV area. OHFV belongs to the mammalian tick‐borne flaviviruses and the ecological group of arboviruses. The problem concerning the origin of OHFV remains unresolved to date. This study analyzed all nucleotide sequences of the OHFV genome obtained in the present study and available in GenBank, including the E gene fragment and the amino acid sequences of the surface glycoprotein encoded by it. The conclusions, based on the clusteron approach, suggest that OHFV originated directly from the TBEV of the Far Eastern subtype due to the host‐jump phenomenon, that is, through a rapid change from an arthropod host,Ixodes persulcatus, to a rodent,O. zibethicus. The muskrat was introduced to Western Siberia in the second half of the 1930s. The peculiarities of the biology and ecology of the muskrat in the new habitat became the reason for the TBEV cross‐species transmission. Calculations show that host‐jumping occurred between 1931 and 1947 and accompanied a cascade of adaptive amino acid substitutions in protein E. As a result, the virus changed its transmission to contact, alimentary, and airborne routes. Based on the data obtained, OHFV would be more correctly attributed to zoonotic viruses transmitted by rodents and, accordingly, to the ecological group of roboviruses.
Age‐dependency of EHRA improvement based on quality of life at diagnosis of atrial fibrillation
Authors: Theunissen Luc J. H. J. , Cremers Henricus‐Paul , van Veghel Dennis , van der Voort Pepijn H. , Polak Peter E. , de Jong Sylvie F. A. M. S. , Smits Geert , Dijkmans Jos , Kemps Hareld M. C. , Dekker Lukas R. C. , van de Pol Jeroen A. A.
Published: January 2022

Background

In this study, the relationship between AF‐related quality of life (AFEQT) at baseline in AF‐patients and the improvement on perceived symptoms and general state of health (EHRA, European Heart Rhythm Association score) at 12 months was assessed across predefined age categories.

Methods

Between November 2014 and October 2019 patients diagnosed with AF de novo in four hospitals embedded within the Netherlands Heart Network were prospectively followed for 12 months. These AF‐patients were categorized into quartiles based on their AFEQT score at diagnosis and EHRA score was measured at diagnosis and 12 months of follow‐up. Stratified analyses were performed using age categories (<65 vs. ≥65 years; <75 vs. ≥75 years).

Results

In total, 203/483 (42.0%) AF‐patients improved in EHRA score after 12 months of follow‐up. AF‐patients in the lowest AFEQT quartile were more likely to improve, compared to patients in the highest AFEQT quartile (OR [95%CI]:4.73 [2.63–8.50]). Furthermore, patients ≥65 years and patients <75 years at diagnosis with lower AFEQT scores at baseline were most likely to improve in EHRA score after 12 months, compared to similarly aged patients with higher AFEQT scores at baseline.

Conclusion

The present study indicates that AF‐patients with a lower quality of life at diagnosis were most likely to improve their EHRA score after 12 months. This effect was most prominent in patients ≥65 years of age and patients <75 years of age, compared to patients >65 and ≥75 years, respectively. Future research should focus on further defining characteristics of these age groups to enable the implementation of age‐tailored treatment.
Do sick coworkers make us help others?: Investigating the critical roles of citizenship pressure and psychological detachment
Authors: Boekhorst Janet A. , Halinski Michael
Published: January 2022

Although researchers have started to uncover the positive effects of presenteeism, research has yet to unearth the positive implications of coworker presenteeism. We draw from social information processing theory to hypothesize that coworker presenteeism has a positive indirect effect on organizational citizenship behaviors directed towards the organization (OCBOs) and other individuals (OCBIs) via citizenship pressure. Building on these hypotheses, we further theorize that the indirect effect of coworker presenteeism on OCBOs and OCBIs differ when employees are psychologically detached from their organization. Based on data collected using a time‐separated research design (n = 277 employees), the results reveal that coworker presenteeism has a positive indirect effect on both forms of OCBs via citizenship pressure. The results further demonstrate that the indirect effect of coworker presenteeism on OCBIs via citizenship pressure strengthens for employees who are psychologically detached from their organization. Importantly, this research shows that there are positive behavioral implications associated with coworker presenteeism.
Towards better characterization of global warming impacts in the environment through climate classifications with improved global models
Authors: Navarro Andrés , Merino Andrés , Sánchez José Luis , García‐Ortega Eduardo , Martín Raúl , Tapiador Francisco J.
Published: January 2022

Climate classifications are useful to synthesize the physical state of the climate with a proxy that can be directly related to biota. However, they present a potential drawback, namely a strong sensitivity because of the use of hard thresholds (step functions). Thus, minor discrepancies in the base data produce large differences in the type of climate. However, such an a priori limitation is also a strength because such sensitivity can be used to better gauge model performance. Although previous attempts of classifying climates of the world using global climate model outputs were encouraging, the applicability of their classifications to impact studies has been limited by past model issues. Notwithstanding the persistence of certain imperfections and limitations in current models, the high‐quality physical simulations from phase six of the Coupled Intercomparison Project (CMIP6) has opened new possibilities in the field, thanks to their improved representation of atmospheric and oceanic physics. The purpose of this paper is twofold: to show that climate classifications from CMIP6 are sufficiently robust for use in impact studies, and to use those classifications for identifying error sources and potential issues that deserve further attention in models. Thus, 52 CMIP6 climate models were evaluated by using three climate classifications schemes, classical Köppen, extended‐Köppen, and modified Thornthwaite. We first assessed model ability to reproduce present climate types by comparing their outputs with observational data. Models performed best for the Köppen and extended‐Köppen classification methods (Cohen's kappa κ = 0.7), and had moderate scores for the Thornthwaite climate classification (κ = 0.4). By tracing back the observed biases, we were able to pinpoint the misrepresentation of dry climates as a major source of error. Another finding was that most models still had some difficulties in representing the seasonal variability of precipitation over several monsoonal regions, thereby yielding the wrong climate type there. Models were also evaluated for future climate. Substantial changes in climate types are projected in the SSP5‐8.5 scenario. These changes include a shrinkage of polar/frigid climates (22%) and an increase of dry climates (7%).
Exploring the factors that hinder Lean improvement initiatives in a job shop environment: A qualitative case study of a Malaysian company
Authors: Abd Samad Mohd Surhardi Effandy , Othman Rosly
Published: January 2022

Job shop production faces various challenges regarding the use of lean manufacturing (Lean) initiatives to sustain a competitive advantage; losing the ability to maintain continual improvement of longstanding initiatives is one of the most significant. This study explores how Lean improvement initiatives can be affected by years of indifferent treatment. Consisting of a single qualitative case study conducted in a Malaysian company that has implemented Lean initiatives for more than 20 years, our findings reveal that Lean implementations in job shop environments can deteriorate over time. Our analysis identifies three overarching themes. First, even though the company has many years' experience of lean implementation, a lack of organizational engagement hindered further improvements. Second, the resource capabilities provided, became outdated, and in poor condition. Third, the company saw a rapidly diminishing level of commitment among its workers. Thus, although the company had previously enjoyed some success in implementing Lean, its ability to keep the momentum behind its initiatives began to fade. The study will help guide practitioner's actions when implementing Lean initiatives, and will enhance the knowledge of issues related to long term Lean implementations in job shop production.
Identification and characterization of the inhibitory effect of ART on colorectal cancer cells using Raman spectroscopy
Authors: Chai Senmao , Sun Xiaodong , Fu Chuhua , Xu Qianqian , Ren Zijing , Xie Lixia , Ge Jingjing , Sang Ming
Published: January 2022

Raman spectroscopy (RS) has been used in clinical diagnostics, tissue engineering, and toxicology experiments owing to its label‐free, low‐destructive, high sensitivity, and strong specificity. Nonetheless, their application has been limited because of the integrated analysis of biological experimental methods and RS. In this study, it was challenged that applied RS in combination with biological experiments to distinguish colorectal cancer (CC) cells from which treated with artesunate (ART), which has obvious antitumor effects. Heavy water (D2O) was used to detect changes in colorectal cancer cell metabolism. The Raman spectral intensity of the C–D band at 2100–2300 cm−1 was significantly weakened in CC (SW480, SW620, and HCT116) treated with ART. According to the CCK‐8, wound healing, and Transwell assays, the activity of SW480 and SW620 cells was significantly inhibited by ART. Through literature tracking and transcriptome sequencing, multiple signal pathways of SW480 and SW620 cells have changed significantly after treatment with ART, such as “apoptotic signaling pathway,” “cell cycle phase transition,” “mitochondrial part,” and “mRNA metabolic process.” The Raman peak area significantly decreased at 490 cm−1, 746 cm−1, 1126 cm−1, 1311 cm−1, 1337 cm−1, and 1582 cm−1 in SW480 and SW620 cells treated with ART. It showed that these Raman bands are associated with ART‐induced apoptosis‐related signaling pathways. In addition, we found that application of the RS in cell type identification will be prosperous. By integrating RS with biological mechanisms, its application in the biomedical field is increasing, and its significance in biological sample detection has become more prominent.
Doppler Imaging Assessment of Changes of Blood Flow in Adenomyosis After Higher‐Dose Oxytocin: A Randomized Controlled Trial
Authors: Li JunShu , Chen JinYun , Wang Yong , Hu Liang , Zhang Rong , Chen WenZhi
Published: January 2022

Objectives

To assess the changes of blood flow in adenomyosis (AM) after higher‐dose oxytocin (OT) in different doses, and to evaluate the safety for patients.

Methods

A total of 124 patients with AM were randomly divided into 4 groups with continuous intravenous infusion of OT as 0.06, 0.12, 0.24 and 0.36 U/min, respectively. The changes of arteries of AM before and after intravenous infusion of OT were observed by color Doppler ultrasound. The changes of blood flow volume of the artery of AM before and after intravenous infusion of OT were compared among the 4 groups, and the vital signs and adverse drug reactions were monitored during intravenous drip.

Results

During the trial, no severe adverse reactions occurred and the vital signs of all the patients were stable. Among the 4 groups, it was found that there was a significant difference in the change of blood flow volume of blood artery in AM lesions between 0.06 U/min OT group and the other three groups after intravenous drip of OT (P < .05), but there was no significant difference in blood flow volume among the three groups (P > .05), and the difference of adverse drug reactions was statistically significant with the increase of OT dose (P < .05).

Conclusion

OT can effectively reduce the blood flow volume of AM lesions, and continuous intravenous infusion of 0.12 U/min OT is an appropriate dose that can not only minimize the blood flow volume but also reduce the incidence of adverse drug reactions.
Shear Wave Elastography of the Coracohumeral Ligament With Frozen Shoulder in Different Stages
Authors: Zhang Jingfeng , Zhang Lei , Guo Fanglan , Zhang Tian
Published: January 2022

Objectives

To study the shear wave elastography (SWE) of the coracohumeral ligament (CHL) in different stages of frozen shoulder and to analyze its correlation with the visual analogue scale (VAS) score and shoulder range of motion (ROM).

Methods

Sixty‐four patients with frozen shoulder were divided into three stages: stage I (freezing phase), stage II (frozen phase), and stage III (thawing phase). The SWE of the CHL of the affected and healthy sides was measured and compared in the different stages. The VAS score and ROM of the affected side were evaluated, and their correlation with the SWE of the CHL was analyzed in the different stages.

Results

In stage I frozen shoulder, the SWE of the CHL on the affected side was lower than that on the healthy side, while in stages II and III, the SWE on the affected side was higher (P = .001 for all). The SWE of the CHL of the affected side was different across the three stages; the SWE in stages II and III higher than that in stage I (P < .01), while the difference between stages II and III was not significant (P > .05). The SWE of the CHL of the affected side was negatively correlated with the VAS score but not with forward flexion (Ff), external rotation (Er) or internal rotation (Ir) in stage I; in stages II and III, it was positively correlated with the VAS score and negatively correlated with Ff, Er, and Ir.

Conclusions

The CHL stiffness of the affected side and its correlation with the shoulder VAS score and ROM are different for different stages of frozen shoulder.
Revised equation of enzymatic kinetics and thermodynamic mechanisms for directed evolution of enzymes
Authors: Zhao Qinyi
Published: January 2022

The equation of enzymatic kinetics is revised, and thermodynamic mechanisms of directed evolution of enzymes are proposed based on both that and the thermodynamic model of enzyme action. In theory, there are two mechanisms of enzymes to improve its catalysis efficiency in directed evolution. The first refers to the change of activation energy of enzymatic reactions. The modulation of structural compatibility between enzyme and substrate serves as the second mechanism and the major motivation for enzymes to enhance their catalysis in situations of directed evolution.