bluuebunny/crossref_metadata_2025 huggingface dataset:
Legal Concepts
Authors: Fredman FBA KC Sandra
Published: January 2023

This chapter develops an understanding of direct discrimination (disparate treatment) and indirect discrimination (disparate impact) in different jurisdictions, and examines the extent to which they can achieve the four-dimensional understanding of equality. Although judges have described direct discrimination as relatively simple, courts have disagreed on some of its basic elements, particularly the role of motive or intention and whether and how direct discrimination can be legitimately justified. In whatever form, it remains limited by its adherence to the principle that likes should be treated alike, for example because of the need for a comparator; and the possibility of responding to a breach by treating everyone equally badly. These issues are explored in Section II. Section III critically assesses indirect discrimination from a comparative perspective across the jurisdictions highlighted in this book and its relationship with direct discrimination. Here, too, it examines the role of intention, how disparate impact is measured, and the standards of scrutiny to justify indirect discrimination, as well as examining the aims and objectives of the concept. Section IV examines ways in which different jurisdictions have relaxed the boundaries between the two concepts, paying particular attention to Canada, the EU, and the ECHR.
The Insanity Defence in English Law
Authors: Mackay Ronnie
Published: January 2023

This chapter discusses the legal development of the defence of insanity in England and Wales which is based on the famous M’Naghten Rules. As such it contains an analysis of problems that have arisen in the application of the insanity and automatism defences through a discussion of recent case law, including an analysis of how the ‘external factor’ doctrine has influenced the distinction between sane and insane automartism. It also includes an evaluation of the author’s empirical research on the defence, together with a discussion of how a new test for the insanity plea was introduced as a result of litigation in the Channel Island of Jersey.
Reforming the Insanity Defence in England and Wales
Authors: Ormerod David , Dsouza Mark
Published: January 2023

English law’s insanity defence has been subjected to sustained and cogent criticism. It is outdated in its understanding of psychiatry and was devised for trial procedures that are unrecognizable to those familiar with modern day practice. The defence is little used but has generated a disproportionate number of appeals. It creates arbitrary distinctions in application by its requirement for a ‘disease of the mind’, and its relationship with sane automatism and pleas based on intoxication is complex and incoherent. Controversially it imposes a legal burden of proof on the defendant. The scope for reform is obvious. With an increasingly enlightened attitude to mental health issues in the criminal justice system, there is an opportunity for law reform to create a defence which deals fairly and equitably with mentally disordered offenders. The Law Commission for England and Wales—whose statutory function is to ensure that the law is as fair, modern, and simple as possible—examined the defence and prepared a discussion paper tentatively proposing a new defence for someone ‘not criminally responsible by reason of medical condition’. This chapter explores the Commission’s work and assesses the prospects for further reform and legislation.
21st-Century Policing and Crime Control
Authors: Braga Anthony A. , Cook Philip J.
Published: January 2023

Policing has evolved during the past few decades in a variety of ways. The police have become less corrupt, better educated, more professional, better paid, and far more diverse with respect to race and sex. They have become more respectful of citizen rights due to exclusionary rules, citizen review boards, consent decrees, and other accountability measures. Police are also more effective in crime control due to improved technology, greater resources, and better strategies. However, challenges remain. Crime control is a co-production process, and community cooperation in investigations is essential. Unfortunately, communities most affected by gun violence generally do not trust the police and fear retaliation for cooperation with the police. Community policing and procedural justice may be helpful in repairing frayed police–community relations. Police also need to be properly motivated and guided to control crime. Low morale undermines police proactivity, and new policing approaches can be limited by union restrictions.
Strengthening the Investigation of Shootings
Authors: Braga Anthony A. , Cook Philip J.
Published: January 2023

Low clearance rates for fatal and nonfatal shootings are a deadly problem in U.S. cities. Detectives attempting to solve gun assaults and homicides have more forensic and technological tools at their disposal than their predecessors from a few decades ago. Despite these new tools, clearance rates are dismally low in many cities. Finding cooperative witnesses remains a key challenge in building strong cases against shooters. The failure to arrest and convict undermines the deterrent effect of the law. Unsolved shootings also contribute to cycles of urban gun violence; deprive victims and their families of justice; and erode trust in the police, which further undermines witness cooperation with investigations. Police departments must invest additional resources in the investigation of fatal and nonfatal shootings. When additional investigative effort is expended, police can improve their success in gaining the cooperation of key witnesses and increase the amount of forensic evidence collected and analyzed.
The rocky road to translational science: An analysis of Clinical and Translational Science Awards
Authors: Kim Yeon Hak , Lee You-Na , Woo Seokkyun
Published: January 2023

Studies point out that the productivity decline in biomedicine is in significant part due to difficulties in translating basic science into clinical application. To promote translational research, the US NIH launched the Clinical and Translational Science Awards (CTSA) program in 2006. Prior evaluations of the CTSA program often assumed that the key to translation is inter-organizational collaboration or multidisciplinarity; hence, changes in either of these were measured as evidence of translational science. However, using novel measures of translational science, this study examines the relationship between CTSAs and translational science per se. We define ‘translational science’ as basic science that has translational features, and we employ two distinct, complementary measures of translational science based on publication data. Using 115 Carnegie R1 universities and their translational science publications, we find that receiving a CTSA does not obviously cause receiving institutions to conduct more translational science. Furthermore, our Principal Investigator-level analysis shows that those who received direct support from the CTSA program had already generated more translational science than others and that their research behavior did not change significantly after receiving a CTSA. Future evaluation research can adopt our novel measures of translational science and evaluation research design in the assessment of translational research activities. Finally, we conclude with a discussion of the implications of our findings for science governance.
ABSORBED DOSE AND IMAGE QUALITY ACCORDING TO THE SCAN MODE AND SHIELD POSITION IN PEDIATRIC BRAIN COMPUTED TOMOGRAPHY SCANS
Authors: Bae Eunmi , Cho Youngkwon , Kim Sungchul
Published: January 2023

In this study, computed tomography dose index (CTDIvol), dose-length product (DLP), organ dose and signal-to-noise ratio (SNR) were measured in pediatric brain helical and volumetric CT scans using a pediatric phantom (equivalent to a 10-year-old) and optically stimulated luminescence dosemeters (OSLD) as the scan protocol used in Hospital A. Volumetric scans showed lower CTDIvol, DLP and organ dose than helical scans, and the SNR showed similar results. The organ doses were lower in the phantoms protected with front, rear or front and rear shielding than in those without shielding. However, no statistically significant differences were found among the different shield locations. In pediatric brain CT scans, to reduce exposure dose and patient discomfort while maintaining image quality, a volumetric scan rather than a helical scan was preferred, and a good shielding effect was observed with front or rear shielding.
Pain specialist management of sexual pain–II. Interventional
Authors: Vogel John J
Published: January 2023

Introduction

Treatment of female sexual pain often requires the use of diverse modalities crossing multiple medical disciplines. Interventional procedures are important in the diagnosis and treatment of female sexual pain. Pain specialists and other medical specialties can provide these capabilities.

Objectives

To provide a current summary of the procedures used in the diagnosis and treatment of female sexual pain.

Methods

The internet, PubMed, and the Cochrane Library were searched for relevant articles on female sexual pain within the clinical purview and scope of the practice of pain management.

Results

A thorough review of the literature was conducted to include basic science studies, clinical trials, systematic reviews, consensus statements, and case reports. An effort was made to also include a sampling of information on real-world patient self-directed therapies. Descriptions of interventional procedures for the diagnosis and treatment of sexual pain were made and clinical studies reviewed. The evidence for the use of various interventional treatment strategies for sexual pain was assessed.

Conclusions

The process of care for female sexual pain employs an interdisciplinary biopsychosocial model that includes a role for interventional procedures commonly performed by pain management specialists. These specialists are a resource of knowledge, skills, and abilities that can be used to improve the care of women with chronic sexual pain.
NX Trichothecenes Are Required for Fusarium graminearum Infection of Wheat
Authors: Hao Guixia , McCormick Susan , Tiley Helene , Gutiérrez Santiago , Yulfo-Soto Gabdiel , Vaughan Martha M. , Ward Todd J.
Published: January 2023

Fusarium graminearum causes Fusarium head blight (FHB) on wheat and barley and contaminates grains with various mycotoxins that are toxic to humans and animals. Deoxynivalenol (DON), a type B trichothecene, is an essential virulence factor that is required for F. graminearum to spread within a wheat head. Recently, novel type A trichothecenes NX-2 and NX-3 (NX) have been found in F. graminearum. NX trichothecenes lack a keto group at the C8 position. To determine if NX trichothecenes play a role similar to that of DON during F. graminearum infection, deletion mutants of TRI5, the first gene for trichothecene biosynthesis, were generated from strains PH-1, NRRL46422, and NRRL44211 (hereafter 44211) representing the 15-acetyl-DON, 3-acetyl-DON, and NX chemotypes. No trichothecene production was detected in any of the Δ tri5 mutants in cultures or inoculated wheat heads. FHB symptoms were restricted to the inoculated wheat spikelets when point-inoculated with the Δ tri5 mutants, confirming the necessity of NX and DON for FHB spread. Furthermore, whole-head dip inoculations revealed significant reductions in disease and fungal biomass in wheat heads inoculated with 44211Δ tri5 compared with 44211. Introduction of the native 44211 TRI5 and a Trichoderma arundinaceum TRI5 ortholog in the 44211Δ tri5 mutant complemented trichothecene production in vitro; however, introducing both TRI5 partially restored wild-type levels of NX in infected heads. Our results demonstrate that NX trichothecenes play an important role in Fusarium graminearum initial infection as well as FHB spread. Thus, TRI5 may serve as an ideal target to control plant infection, FHB spread, and mycotoxin production simultaneously.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Systematic Characterization of Multi-Rust Resistance Genes from a ‘Parula × Thatcher’ Population with a High-Density Genetic Map
Authors: Zhang Wentao , Boyle Kerry , Gao Peng , Polley Brittany , Brost Jennifer M. , Francis Tammy , Sidebottom Christine , McCallum Brent D. , Kutcher Hadley R. , Randhawa Harpinder , Fetch Tom G. , Ferrie Alison M. R. , Fobert Pierre R.
Published: January 2023

Pyramiding multiple resistant genes has been proposed as the most effective way to control wheat rust diseases globally. Identifying the most effective pyramids is challenged by the large pool of rust resistance genes and limited information about their mechanisms of resistance and interactions. Here, using a high-density genetic map, a double haploid population, and multi-rust field testing, we aimed to systematically characterize the most effective gene pyramids for rust resistance from the durable multi-rust resistant CIMMYT cultivar Parula. We revealed that the Parula resistance gene pyramid contains Lr34/Yr18/Sr57 ( Lr34), Lr46/Yr29/Sr58 ( Lr46), Lr27/Yr30/Sr2 ( Sr2), and Lr68. The efficacy, magnitude of effect, and interactions varied for the three rust diseases. A subpopulation mapping approach was applied to characterize the complex interactions of the resistance genes by controlling for the effect of Lr34. Using this approach, we found that Lr34 and Lr68 have a strong additive effect for leaf rust, whereas no additive effects were observed for any rusts between Lr34 and Lr46. Lr34 combined synergistically with Sr12 from Thatcher for stem rust, whereas the additive effect of Lr34 and Sr2 was dependent on the type of rust and environment. Two novel leaf rust quantitative trait loci (QTLs) from Parula were identified in this study, a stable QTL QLr-7BS and QLr-5AS, which showed Lr34 dependent expression. With these findings, we propose combining two to three high-value genes from Canadian wheat (e.g., Sr12 from Thatcher) with a foundational multi-adult plant resistance cassette for desirable and durable resistance to all three rusts in Canadian wheat.
Development and Validation of E-Probes with the MiFi System for Detection of Ralstonia solanacearum Species Complex in Blueberries
Authors: Bocsanczy Ana M. , Espindola Andres S. , Cardwell Kitty , Norman David J.
Published: January 2023

The blueberry industry, a fast-growing industry in Florida, is threatened by bacterial wilt, caused by the Ralstonia solanacearum species complex (RSSC). In 2016, distinct RSSC populations were found in Florida causing disease in blueberry. Currently, there are no tools that discriminate between RSSC populations pathogenic to blueberry and other RSSC strains. Early detection of specific RSSC strains is critical, and the Microbe Finder (MiFi) web application is a sensitive and specific tool used to detect known target pathogens in sequenced samples. MiFi is used to develop e-probes and subsequently query sample metagenomes with them. We report the development and validation of e-probes for three different RSSC populations pathogenic to blueberry using the MiFi platform. We also present preliminary data to assess the feasibility of a cost-effective integrated diagnostics system, MiFi, in combination with MinION, a pocket-sized, portable sequencer. The e-probes were validated in silico, generating simulated metagenomes; in vitro by using blueberry DNA spiked with pathogen DNA; and in vivo with soil and stem samples. We tested several methods of DNA extraction for soil and blueberry stems and several MinION libraries with or without barcodes. MiFi blueberry e-probes effectively identified target pathogens at a very specific level with high sensitivity. The MiFi system combined with MinION sequencing using Flongle cells was optimized to produce results in one day. Further optimization and tests can improve greatly the cost effectiveness and flexibility of this system by adding e-probes to test for new blueberry strains and many other pathogens affecting blueberry in one test.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Clinical characteristics and in-hospital management strategies in patients with acute coronary syndrome: results from 2,096 accredited Chest Pain Centers in China from 2016 to 2021
Authors: Li Linjie , Zhou Xin , Jin Zhengyang , A Geru , Sun Pengfei , Wang Zhuoqun , Li Yongle , Xu Chengyi , Su Xi , Yang Qing , Huo Yong
Published: January 2023

Background and purpose:

The Chest Pain Center accreditation project was launched in 2011 in China as a nationwide effort to improve clinical management of acute chest pain patients. In this study, we summarize the clinical characteristics and in-hospital outcomes of patients undergoing treatment for acute coronary syndrome (ACS) in Chest Pain Centers in China.

Methods:

Data were based on the Chinese Cardiovascular Association (CCA) Database-Chest Pain Center of 1,745,118 ACS patients admitted at 2,096 accredited Chest Pain Center between January 1, 2016, and December 31, 2021. Patient characteristics, time delays, treatment, and outcomes were analyzed using descriptive analysis.

Results:

The final analysis included a total of 1,745,118 patients, 699,476 patients (40.1%) with ST segment elevation myocardial infarction (STEMI), 349,572 (20.0%) with non-ST segment elevation myocardial infarction (NSTEMI), and 696,070 (39.9%) with unstable angina (UA). Electrocardiogram (ECG) was conducted in 89.4% of the patients within 10 min after first medical contact. For STEMI patients, the median door-to-wire crossing time was 72.1 (53.1 to 91.9) min and the median first medical contact-to-needle time was 32.3 (23.8 to 58.6) min. In-hospital mortality was 2.0% in the overall analysis, 3.6% for STEMI, 2.1% for NSTEMI, and 0.3% for UA. Primary percutaneous coronary intervention (PCI) was conducted in 62.8% of STEMI patients, with increasing rate in grade I and II hospitals over the 6-year study period. Patients treated with thrombolysis had significantly higher mortality than those treated with PCI and thrombolysis combined with PCI. The development of Chest Pain Centers varied substantially across geographic regions.

Conclusions:

Based on CCA Database-Chest Pain Center, the current study provided an overall description of the clinical characteristics of ACS patients in China. The results on management pattern and in-hospital outcomes of STEMI patients identified important areas for further improvement in ACS patient management in China.
Age and Mental Health Symptoms Among Chinese Persons With HIV: The Mediating and Moderating Role of Perceived Discrimination
Authors: Han Shuyu , Pei Yaolin , Wang Jianyun , Hu Yan , Zhu Zheng , Qi Xiang , Yang Zhongfang , Wu Bei
Published: January 2023

The association between age and mental health symptoms among persons with HIV (PWH) is inconsistent, and little is known about the mediators and moderators of this association. This study aimed to examine the association between age and mental health symptoms, as well as the mediators and moderators of perceived discrimination. Data were from 1,304 PWH who completed a cross-sectional survey in five areas of China. Multiple linear regressions showed that younger age was significantly associated with more severe mental health symptoms and that perceived discrimination moderated this relationship. The Sobel test showed that perceived discrimination also mediated the association between age and mental health symptoms. Our study indicates that perceived discrimination shapes the association between age and mental health symptoms among PWH and highlights the importance of designing age-tailored mental health intervention strategies for perceived discrimination among young PWH. Interventions addressing discrimination are necessary to help improve mental health, especially for young PWH.
Nurse-facilitated preexposure prophylaxis delivery for adolescent girls and young women seeking contraception at retail pharmacies in Kisumu, Kenya
Authors: Pintye Jillian , Odoyo Josephine , Nyerere Bernard , Achieng Pauline , Araka Evelyne , Omondi Christine , Ortblad Katrina F. , Mugambi Melissa L. , Baeten Jared M. , Bukusi Elizabeth A.
Published: January 2023

Objective:

We evaluated preexposure prophylaxis (PrEP) uptake, initiation, and continuation within a nurse-facilitated pharmacy-based delivery model for Kenyan adolescent girls and young women (AGYW) seeking contraception at retail pharmacies.

Methods:

From October 2020 to March 2021, PrEP-trained nurses were stationed at three retail pharmacies in Kisumu, Kenya. AGYW (aged 15–24 years) purchasing contraception (emergency contraception, oral contraceptive pills, injectables, implants, condoms) were counseled on PrEP, completed HIV testing, and offered a free 1-month supply of PrEP pills per national guidelines by nurses under supervision of a remote physician. We evaluated uptake among all AGYW offered PrEP. At 30 days after uptake, we evaluated PrEP use initiation and plans for continuation.

Results:

We enrolled 235 AGYW clients who were HIV-negative and purchasing contraception at pharmacies. Emergency contraception was the most frequently purchased contraceptive (35%). Median age was 22 years (IQR 19–23), 44% were currently in school, and 33% currently had multiple sexual partners. One-fourth (24%) exchanged sex for money or favors and 14% had sex while intoxicated in the prior 6 months. Overall, PrEP uptake was 85%; at 1 month, 82% had initiated PrEP use and 68% planned to continue use. Among those initiating PrEP, 69% were willing to pay for PrEP at retail pharmacies (median KES 150, IQR 100–200) even if available for free at public sector facilities.

Conclusion:

In this evaluation of nurse-facilitated PrEP delivery at pharmacies in Kenya, a substantial proportion of AGYW who purchased contraception subsequently initiated PrEP, planned to continue use, and were willing to pay for PrEP.
Variation in hospice use among trauma centers may impact analysis of geriatric trauma outcomes: An analysis of 1,961,228 Centers for Medicare and Medicaid Services hospitalizations from 2,317 facilities
Authors: Fakhry Samir M. , Shen Yan , Wyse Ransom J. , Garland Jeneva M. , Watts Dorraine D.
Published: January 2023

BACKGROUND

Defining discharges to hospice as “deaths” is vital for properly assessing trauma center outcomes. This is critical with older patients as a higher proportion is discharged to hospice. The goals of this study were to measure rates of hospice use, evaluate hospice discharge rates by trauma center level, and identify variables affecting hospice use in geriatric trauma.

METHODS

Patients from the Centers for Medicare and Medicaid Services Inpatient Standard Analytical Files for 2017 to 2019, 65 years or older, with ≥1 injury International Classification of Diseases, Tenth Revision, code, at hospitals with ≥50 trauma patients per year were selected. Total deaths was defined as inpatient deaths plus hospice discharges. Dominance analysis identified the most important contributors to a model of hospice use.

RESULTS

A total of 1.96 million hospitalizations from 2,317 hospitals (Level I, 10%; II, 14%; III, 18%; IV, 7%; none, 51%) were included. Level I's had significantly lower raw hospice discharge values compared with Levels II and III (I, 0.030; II, 0.035; III, 0.035; p < 0.05) but not Level IV (0.032) or nontrauma centers (0.030) (p > 0.05). Adjusted Level I hospice discharge rates were lower than all other facility types (Level I, 0.026; II, 0.031; III, 0.034; IV, 0.033; nontrauma, 0.030; p < 0.05). Hospice discharges as a proportion of total deaths varied by level and were lowest (0.38) at Level I centers. Dominance analysis showed that proportion of patients with Injury Severity Score of >15 contributed most to explaining hospice utilization rates (3.2%) followed by trauma center level (2.3%), proportion White (1.9%), proportion female (1.5%), and urban/rural setting (1.4%).

CONCLUSION

In this near population-based geriatric trauma analysis, Level I centers had the lowest hospice discharge rate, but hospice discharge rates varied significantly by trauma level and should be included in mortality assessments of hospital outcomes. As the population ages, accurate assessment of geriatric trauma outcomes becomes more critical. Further studies are needed to evaluate the optimal utilization of hospice in end-of-life decision making for geriatric trauma.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level II.
Vibrio sinus sp. nov., a marine bacterium isolated from coastal seawater
Authors: Wang Wei , Zhao Wenbin , Cao Bingbing , Liu Ronghua , Cheng Haojin , Tian Peng , Xiao Jiaguang , Xu Ziqing , Wang Xiaolei , Niu Wentao
Published: January 2023

A Gram–straining–negative, facultatively anaerobic, motile by means of a polar flagellum and rod-shaped marine bacterium, designated S4M6T, was isolated from surface seawater collected in Dongshan Bay (Fujian, PR China). Phylogenetic analysis based on 16S rRNA genes, phylogenomic analysis of single-copy gene families and whole genome data indicated that S4M6T represented a member of the genus

Vibrio

. The closest phylogenetic relatives of S4M6T were

Vibrio marisflavi

CGMCC 1.8994T (97.8 % 16S rRNA gene sequence pairwise similarity),

Vibrio variabilis

LMG 25438T (96.9 %),

Vibrio gangliei

SZDIS-1T (96.2 %) and

Vibrio aestivus

M22T (96.1 %). The growth of S4M6T occurred at 15–35 °C (optimum 28 °C), pH 4.0–9.0 (optimum 5.0–7.0) and in the presence of 2–5 % (w/v) NaCl (optimum 3 %). The predominant fatty acids (>10 %) are C16 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 
1ω6c) and summed feature 8 (C18 : 1ω7c and/or C18 : 
1ω6c). The DNA G+C content of the assembled genomic sequences was 43.4 % for S4M6T. Average nucleotide identity (ANI) values between S4M6T and the reference species were lower than the threshold for species delineation (95–96 %); in silico DNA–DNA hybridization further indicated that S4M6T had less than 70 % similarity to its relatives. On the basis of the polyphasic evidence, strain S4M6T is proposed to represent a novel species of the genus

Vibrio

, for which the name Vibrio sinus sp. nov. is proposed. The type strain is S4M6T (= KCTC 92312T= MCCC 1K06167T).
Covalent inhibition by a natural product-inspired latent electrophile
Authors: Byun David P , Ritchie Jennifer , Holewinski Ronald , Kim Hong-Rae , Tagirasa Ravichandra , Ivanic Joseph , Weekley Claire M , Parker Michael W , Adresson Thorkell , Yoo Euna
Published: January 2023

Strategies to target specific protein cysteines are critical to covalent probe and drug discovery. 3-bromo-4,5-dihydroxazole is a natural product-inspired, synthetically accessible electrophilic moiety that has previously been shown to react with nucleophilic cysteines in the active site of purified enzymes. Here we define the global cysteine reactivity and selectivity of a set of 3-bromo-4,5-dihydroxazole-functionalized chemical fragments using competitive chemoproteomic profiling methods. Our study demonstrates that 3-bromo-4,5-dihydroxazoles capably engage reactive cysteine residues in the human proteome and the selectivity landscape of cysteines liganded by 3-bromo-4,5-dihydroxazoles is distinct from that of haloacetamide electrophiles. Given its tempered reactivity, 3-bromo-4,5-dihydroxazoles showed restricted, selective engagement with proteins driven by interactions between a tunable binding element and the complementary protein sites. We further validate that 3-bromo-4,5-dihydroxazoles form covalent conjugates with glutathione S-transferase Pi (GSTP1) and peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), emerging anti-cancer targets. Together, this study expands the spectrum of optimizable chemical tools for covalent ligand discovery and highlights the utility of 3-bromo-4,5-dihydroxazole as a cysteine-reactive electrophile.
HPV and p16 expression association with 5-year survival in oral squamous cell carcinoma patients of North-East India
Authors: Das Rajjyoti , Kumar Rupesh , Rai Avdhesh Kumar , Sarma Anupam , Kakoti Lopamudra , Kataki Amal Chandra , Bhattacharyya Mouchumee , Kalita Manoj
Published: January 2023

Background

In our study, we examined the 5-year survival of OSCC patients with HPV positive or negative status along with p16 protein expression.

Method

A total of 72 biopsy tissue specimens from histologically confirmed oral squamous cell carcinoma (OSCC) patients were collected. HPV detection and genotyping were performed using HPV E6/E7 and HPV-type specific multiplex primer for nested-PCR. Immunohistochemistry evaluation of pl6 was conducted. SPSS statistical software (ver 20) was used for data analysis.

Results

High risk-HPV (hr-HPV) DNA positivity was found in 27.7% (n=20) of OSCC patients. Stage III OSCC patients were 7.80 times more likely to survive 5 years than stage IV patients (OR-7.80 CI-95%; P-0.03). Among the hr-HPV positive OSCC patients, we found that the median survival time for the 1st year (95%), 3 years (78.5%), and 5 years (38.5%) was significantly higher than that of the hr-HPV negative [1st year (78.6%), 3 years (45.2%) and 5 years (38.5%)] OSCC patients (P-0.03 The survival of male patients with hr-HPV positive OSCC is 9.75 times greater than the survival of patients with HPV negative OSCC (OR-9.75; CI-95%; P-0.05). The p16 expression level (low to overexpression) group and negative P16 expression group of OSCC patients have not demonstrated a significant association with 5-year survival.

Conclusion

We conclude that in OSCC cases of North-East India, the presence of hr-HPV in OSCC cases could be a good predictor of 5-year survival rate. Expression of p16 does not appear to have any significant association with 5-year survival.
The role of rare genetic variants enrichment in epilepsies of presumed genetic etiology
Authors: Bundalian Linnaeus , Su Yin-Yuan , Chen Siwei , Velluva Akhil , Kirstein Anna Sophia , Garten Antje , Biskup Saskia , Battke Florian , Lal Dennis , Heyne Henrike O. , Platzer Konrad , Lin Chen-Ching , Lemke Johannes R. , Duc Diana Le ,   Epi25 Collaborative
Published: January 2023

1.

Previous studies suggested that severe epilepsies e.g., developmental and epileptic encephalopathies (DEE) are mainly caused by ultra-rarede novogenetic variants. For milder phenotypes, rare genetic variants could contribute to the phenotype. To determine the importance of rare variants for different epilepsy types, we analyzed a whole-exome sequencing cohort of 9,170 epilepsy-affected individuals and 8,436 controls. Here, we separately analyzed three different groups of epilepsies : severe DEEs, genetic generalized epilepsy (GGE), and non-acquired focal epilepsy (NAFE). We required qualifying rare variants (QRVs) to occur in controls at a minor allele frequency ≤ 1:1,000, to be predicted as deleterious (CADD≥20), and to have an odds ratio in epilepsy cases ≥2. We identified genes enriched with QRVs in DEE (n=21), NAFE (n=72), and GGE (n=32) - the number of enriched genes are found greatest in NAFE and least in DEE. This suggests that rare variants may play a more important role for causality of NAFE than in DEE. Moreover, we found that QRV-carrying genes e.g.,HSGP2, FLNAorTNCare involved in structuring the brain extracellular matrix. The present study confirms an involvement of rare variants for NAFE, while in DEE and GGE, the contribution of such variants appears more limited.
Genome diversity ofLeishmania aethiopica
Authors: Hadermann Amber , Heeren Senne , Maes Ilse , Dujardin Jean-Claude , Domagalska Malgorzata Anna , Van den Broeck Frederik
Published: January 2023

Leishmania aethiopicais a zoonotic Old World parasite transmitted by Phlebotomine sand flies and causing cutaneous leishmaniasis in Ethiopia and Kenya. Despite a range of clinical manifestations and a high prevalence of treatment failure,L. aethiopicais the most neglected species of theLeishmaniagenus in terms of scientific attention. Here, we explored the genome diversity ofL. aethiopicaby analyzing the genomes of twenty isolates from Ethiopia. Phylogenomic analyses identified two strains as interspecific hybrids involvingL. aethiopicaas one parent andL. donovaniandL. tropicarespectively as the other parent. High levels of genome-wide heterozygosity suggest that these two hybrids are equivalent to F1 progeny that propagated mitotically since the initial hybridization event. Analyses of allelic read depths further revealed that theL. aethiopica-L. tropicahybrid was diploid and theL. aethiopica-L. donovanihybrid was triploid, as has been described for other interspecificLeishmaniahybrids. When focusing onL. aethiopica, we show that this species is genetically highly diverse and consists of both asexually evolving strains and groups of recombining parasites. A remarkable observation is that someL. aethiopicastrains showed an extensive loss of heterozygosity across large regions of the chromosomal genome, which likely arose from gene conversion/mitotic recombination. Hence, our prospection ofL. aethiopicagenomics revealed new insights into the genomic consequences of both meiotic and mitotic recombination inLeishmania.
The 3D coarse-graining formulation of interacting elastohydrodynamic filaments and multi-body microhydrodynamics
Authors: Fuchter Paul , Bloomfield-Gadêlha Hermes
Published: January 2023

Elastic filaments are vital to biological, physical and engineering systems, from cilia driving fluid in the lungs to artificial swimmers and micro-robotics. Simulating slender structures requires intricate balance of elastic, body, active, and hydrodynamic moments, all in three-dimensions. Here, we present a generalised 3D coarse-graining formulation that is efficient, simple-to-implement, readily extendable and usable for a wide array of applications. Our method allows for simulation of collections of 3D elastic filaments, capable of full flexural and torsional deformations, coupled non-locally via hydrodynamic interactions, and including multi-body microhydrodynamics of structures with arbitrary geometry. The method exploits the exponential mapping of quaternions for tracking three-dimensional rotations of each interacting element in the system, allowing for computation times up to 150 times faster than a direct quaternion implementation. Spheres are used as a ‘building block’ of both filaments and solid micro-structures for straightforward and intuitive construction of arbitrary three-dimensional geometries present in the environment. We highlight the strengths of the method in a series of non-trivial applications including bi-flagellated swimming, sperm-egg scattering, and particle transport by cilia arrays. Applications to lab-on-a-chip devices, multi-filaments, mono-to-multi flagellated microorganisms, Brownian polymers, and micro-robotics are straightforward. A Matlab code is provided for further customization and generalizations.
Development of a Novel Medium Throughput Flow-Cytometry Based Micro-Neutralisation Test for SARS-CoV-2 with Applications in Clinical Vaccine Trials and Antibody Screening
Authors: O’Reilly Sophie , Kenny Grace , Alrawahneh Tamara , Francois Nathan , Angeliadis Matthew , de Masson d’Autume Valentin , Leon Alejandro Garcia , Feeney Eoin R. , Yousif Obada , Cotter Aoife , de Barra Eoghan , Horgan Mary , Mallon Patrick WG , Gautier Virginie
Published: January 2023

Quantifying neutralising capacity of circulating SARS-COV-2 antibodies is critical in evaluating protective humoral immune responses generated post-infection/post-vaccination. Here we describe a novel medium-throughput flow cytometry-based micro-neutralisation test to evaluate Neutralising Antibody (NAb) responses against live SARS-CoV-2 Wild Type and Variants of Concern (VOC) in convalescent/vaccinated populations. Flow Cytometry-Based Micro-Neutralisation Test (Micro-NT) was performed in 96-well plates using clinical isolates WT-B, WT-B.177.18 and/or VOCs Beta and Omicron. Plasma samples (All Ireland Infectious Diseases (AIID) Cohort) were serially diluted (8 points, half-log) from 1/20 and pre-incubated with SARS-CoV-2 (1h, 37°C). Virus-plasma mixture were added onto VERO E6/VERO E6 TMPRSS2 cells for 18h. Percentage infected cells was analysed by automated flow cytometry following trypsinisation, fixation and SARS-CoV-2 Nucleoprotein intracellular staining. Half-maximal Neutralisation Titres (NT50) were determined using four-parameter logistic regression. Our assay was compared to Plaque Reduction Neutralisation Test (PRNT) and validated against WHO anti-SARS-CoV-2 Immunoglobulin Standards. Using WHO Standards with low, medium or high anti-SARS-CoV-2 IgG, both Micro-NT and PRNT achieved comparable NT50 values. Micro-NT was found to be highly reproducible (inter-assay CV of 11.64%). Screening 190 convalescent samples and 11 COVID-19 naive controls (AIID cohort) we demonstrated that Micro-NT has broad dynamic range differentiating NT50s <1/20 to >1/5000. We could also characterise immune-escape VOC observing up to 10-fold reduction in NT50 against SARS-CoV-2 Beta variant. Our flow cytometry-based Micro-NT is a robust and reliable assay to quantify NAb titres, and has been selected as an endpoint in clinical trials. It has higher throughput (96 well format versus 12 well) and reduced infection time (18h vs 48-96h) compared to the gold standard PRNT.
Crystal structure of a polyglycine hydrolase determined using a RoseTTAFold model
Authors: Dowling Nicole V. , Naumann Todd A. , Price Neil P. J. , Rose David R.
Published: January 2023

Polyglycine hydrolases (PGHs) are secreted fungal proteases that cleave the polyglycine linker of Zea mays ChitA, a defensive chitinase, thus overcoming one mechanism of plant resistance to infection. Despite their importance in agriculture, there has been no previous structural characterization of this family of proteases. The objective of this research was to investigate the proteolytic mechanism and other characteristics by structural and biochemical means. Here, the first atomic structure of a polyglycine hydrolase was identified. It was solved by X-ray crystallography using a RoseTTAFold model, taking advantage of recent technical advances in structure prediction. PGHs are composed of two domains: the N- and C-domains. The N-domain is a novel tertiary fold with an as-yet unknown function that is found across all kingdoms of life. The C-domain shares structural similarities with class C β-lactamases, including a common catalytic nucleophilic serine. In addition to insights into the PGH family and its relationship to β-lactamases, the results demonstrate the power of complementing experimental structure determination with new computational techniques.
How would you respond to stereotype pressure? The effects of perceived occupational stigma on social workers’ proactive behavior in China
Authors: Zhan Jing , Zhao Yue
Published: January 2023

Purpose

The purpose of this study is to explore a balanced understanding of the relationship between perceived occupational stigma and social workers’ proactive behaviors in China. Drawing on cognitive appraisal theory, this study explored the mediating role of threat and challenge appraisals, as well as the moderating role of trait resilience.

Design/methodology/approach

Data were collected using a time-lagged research design. The hypotheses were examined using a sample of 338 social workers in China.

Findings

Perceived occupational stigma is appraised as both a challenge and a threat simultaneously. Challenge appraisal positively mediated perceived occupational stigma and proactive behavior, whereas threat appraisal negatively mediated this relationship. Trait resilience moderated the effect of threat appraisal, suggesting that perceived occupational stigma was appraised as a threat when trait resilience was lower (rather than higher), which then reduced social workers’ proactive behaviors.

Originality/value

This study enriches the literature on perceived occupational stigma by identifying the relationship and mechanism of perceived occupational stigma-proactive behaviors and a boundary condition from the theoretical perspective of cognitive appraisals. It demonstrates both the positive and negative aspects of perceived occupational stigma as appraised by social workers in relation to an important workplace outcome of proactive behaviors. In addition, it offers a fresh approach by exploring perceived occupational stigma from the perspective of social workers.
Entrepreneurial growth aspirations at re-entry after failure
Authors: Fuentelsaz Lucio , González Consuelo , Mickiewicz Tomasz
Published: January 2023

Purpose

Utilising the Theory of Planned Behaviour as the conceptual framework, the authors argue that entrepreneurial financial failure enhances entrepreneurial growth aspirations for the subsequent start-up projects. Furthermore, this effect is particularly strong for individuals rich in human capital, both general and specific; for them, financial failure of an entrepreneurial business is likely to be subsequently transformed into higher entrepreneurial growth aspirations.

Design/methodology/approach

The authors employ multilevel estimation techniques applied to Global Entrepreneurship Monitor data consisting of annual subsamples, each with at least 2,000 observations drawn from the working age population of 95 countries, for the period 2007–2019.

Findings

The results confirm that the experience of financial failure, both individual and societal, leads to higher growth aspirations for subsequent ventures, while exit for opportunity reasons has an even stronger positive effect on growth aspirations. Furthermore, higher education and entrepreneurial experience enhance the positive impact of financial failure on the growth aspirations of subsequent start-ups.

Originality/value

The authors demonstrate that the Theory of Planned Behaviour, which centres on intentions, can be successfully utilised to understand why entrepreneurial failure may be transformed into high growth aspirations for subsequent projects and why this effect may be enhanced by the human capital of the entrepreneur. Furthermore, the authors apply multilevel methods to a large international dataset from Global Entrepreneurship Monitor and produce novel empirical evidence supporting their theoretical predictions.
How do Pakistani drama serials discursively represent domestic violence?
Authors: Ahmad Faiqa
Published: January 2023

Purpose

The objective of this study was to look closely at how domestic violence is represented in Pakistani drama serials to see if portrayals are reinforcing stereotypical and/or patriarchal values, or breaking the rigid norms.

Design/methodology/approach

With the help of dispositive analysis within the critical discourse approach, the prominent and non-dominant discourses about domestic violence were identified and discussed. Episodes from two popular drama serials, Kaisa Yeh Naseeban and Khaas, released in 2019, were watched with special focus on texts on domestic violence alongside objects and actions.

Findings

Analysis showed that both drama serials gave importance to socio-systemic and liberal humanist instrumentalism discourses, which describe domestic violence as a result of social structures and that abuse is used to assert control, respectively. However, some instances were noted where patriarchal values were encouraged.

Originality/value

As media has become a powerful tool of influence and awareness in the recent times, it is imperative that the content watched on it by millions of people be studied and analyzed. It is claimed that Pakistani drama serials with wide following and that are made on social issues around women aim to raise awareness and empower them. Domestic violence is a prevalent issue in Pakistan, and no research till date has examined representation of domestic violence on Pakistani popular media, which may influence response to domestic violence, which this paper aims to do.
Integrating RADAR and optical imagery improve the modelling of carbon stocks in a mopane‐dominated African savannah dry forest
Authors: Gara Tawanda W. , Mpakairi Kudzai S. , Nampira Tinotenda C. , Oduro Appiah Joseph , Muumbe Tasiyiwa P. , Dube Timothy
Published: January 2023

This study examined the integration of two satellite data sets, that is Landsat 7 ETM+ and ALOS PALSAR (Advanced Land Observing Satellite Phased Array type L‐band Synthetic Aperture RADAR) in estimating carbon stocks in mopane woodlands of north‐western Zimbabwe. Mopane woodlands cover large spatial extents and provide ecosystem benefits to the rural economies and grazing resources for both livestock and wildlife. In this study, artificial neural networks (ANN) were used to estimate carbon stocks based on spectral metrics derived from Landsat 7 ETM+ and ALOS PALSAR. To determine the utility of the two satellite‐derived metrics, a two‐pronged modelling framework was adopted. Firstly, we used spectral bands and vegetation indices from the two satellite data sets independently, and subsequently, we integrated the metrics from the two satellite data sets into the final model. Results showed that the ALOS PALSAR (R2 = 0.75 and nRMSE = 0.16) and Landsat ETM+ (R2 = 0.78 and nRMSE = 0.14) derived spectral bands and vegetation indices comparatively yielded accurate estimations of carbon stocks. Integrating spectral bands and vegetation indices from both sensors significantly improved the estimation of carbon stocks (R2 = 0.84 and nRMSE = 0.12). These findings underscore the importance of integrating satellite data in vegetation biophysical assessment and monitoring in poorly documented ecosystems such as the mopane woodlands.
Cultural and outdoor activities in Canada: Who does what?
Authors: Moulin Stéphane
Published: January 2023

This article innovatively combines the analysis of both cultural and outdoor activities in Canada, activities that have been mostly studied separately until now. This study thus feeds into the debate between the distinction framework (focusing on the highbrow/lowbrow opposition) and the omnivorism thesis (distinguishing between omnivorous and univorous groups) in cultural sociology. From Latent Class Analysis (LCA), this study identifies five clusters, which differentiate people practicing either or both cultural and outdoor activities. The clusters are labelled as follow: “tele‐univore,” “digital indoor,” “conventional indoor,” “outdoor univore,” and “omnivore.” Binary logistic regressions reveal that education, age and rural/urban identity are the key factors in identifying who practices which activities. The findings are threefold. First, while confirming the omnivore theory, our results show that cultural capital matters more than economic capital in explaining who participates in which activities. Second, rural people tend to be slightly more engaged than urban people in consumptive and motorized outdoor activities and less in all cultural activities. Third, the shift to digitization and the increase in outdoor activities appears to have exacerbated the divide between older and younger generations.