Submitting Novel Full-Length HLA, MIC, and KIR Alleles with TypeLoader2.

The Immuno Polymorphism Database (IPD) plays a pivotal role for immunogenetics. Due to technical limitations, genotyping often focuses on specific key regions like the antigen recognition domain (ARD) for HLA genotyping, and the databases are populated accordingly. More recently, though, modern next generation sequencing (NGS) assays allow using larger gene segments or even complete genes for genotyping. It is therefore essential that the databases are updated with complete genetic reference sequences to fully serve current and future applications. However, the process of manually annotating and submitting full-length allele sequences to IPD is time-consuming and error-prone, which may discourage HLA-genotyping laboratories or researchers from submitting full-length sequences of novel alleles.Here, we detail the process of preparing and submitting novel HLA, MIC, and KIR alleles to ENA and IPD using TypeLoader2, a convenient software tool developed to streamline this process by automating the sequence annotation, the creation of all necessary files, as well as parts of the submission process itself. The software is freely available from GitHub ( https://github.com/DKMS-LSL/typeloader ).

Drug-facilitated sexual assault in youth nightlife contexts in Spain.

OBJECTIVES: This study aimed to provide epidemiological information on drug-facilitated sexual assault in Spanish youth partying, with a focus on prevalence rates and associated sociodemographic factors. STUDY DESIGN: Cross-sectional study. METHODS: Quota sampling was used to recruit 1601 young people aged 18-35 years in Spain from a digital panel. A validated questionnaire on drug-facilitated sexual assault was used to assess five types of lifetime victimisation experiences while partying. Chi-square and the exact Fisher tests were used to describe the prevalence of victimisation, drug use patterns, and perpetrator profiles. Generalised ordered logistic regression was used to explore factors associated with victimisation, analysed by gender. RESULTS: Half of young women and one-quarter of young men had experienced drug-facilitated sexual assault in their lifetime. Female victimisation due to touching and kissing was notably high, whereas men comprised almost half of the victims of more invasive DFSA experiences involving masturbation, penetration, and oral sex. Opportunism prevailed as the assault tactic, consisting of taking advantage of the victims' incapacity derived from voluntary alcohol use. Among women, risk of victimisation was associated with a lower education level, foreign-born status, and being non-heterosexual. Male victimisation risk was highest among non-heterosexual men. CONCLUSIONS: Drug-facilitated sexual violence in youth nightlife contexts is a serious public health issue in Spain, which requires urgent action. Most assaults involve taking advantage of victims who are incapacitated by the effects of voluntary alcohol consumption. This sexual violence primarily affects women with lower educational levels or those who are foreign-born and non-heterosexual men and women.

Gender inclusivity of ophthalmology journal submission guidelines and associated research metrics.

PURPOSE: This cross-sectional study evaluated the prevalence of inclusive author submission guidelines across ophthalmology journals. METHODS: Journals were identified from the 2021 Journal Citations Report (Clarivate Analytics). Independent reviewers rated each author submission guideline as "inclusive" for satisfying at-least one of six criteria: i) included examples of gender inclusive language; ii) recommended the use of gender-inclusive language; iii) distinguished between sex and gender; iv) provided educational resources on gender-inclusive language; v) provided a policy permitting name changes (e.g., in case of gender and name transition); and/or vi) provided a statement of commitment to inclusivity. The primary objective was to investigate the proportion of journals with "gender-inclusive" author submission guidelines and the elements of the gender-inclusive content within these guidelines. A secondary objective was to review the association between "gender-inclusivity" in author submission guidelines with publisher, origin country, and journal/source/influence metrics (Clarivate Analytics). RESULTS: Across 94 journals, 29.8% journals were rated as inclusive. Inclusive journals had significantly higher relative impact factor, citations, and article influence scores compared to non-inclusive journals. Of the 29.8% of inclusive journals, the three most common domains were inclusion of an inclusivity statement (71.4% of inclusive journals), distinguishing between sex and gender (67.9%), and provision of additional educational resources on gender reporting for authors (60.7%). CONCLUSION: A minority of ophthalmology journals have gender-inclusive author submission guidelines. Ophthalmology journals should update their submission guidelines to advance gender equity of both authors and study participants and promote the inclusion of gender-diverse communities.

Explanations for Gender Differences in Preferences for Submissive Sexual Fantasies.

Women have a stronger preference for sexual submission than men do. In the current studies, we investigated gender differences in fantasies about sexual submission. Replicating previous research, in two studies we found that women expressed a stronger affinity for fantasies about sexual submission than men did. However, controlling for age and several sociocultural factors made the relationship between gender and preference for sexual submission non-significant-that is, we could statistically eliminate the gender difference. These analyses suggest the multiple factors that may influence sexual preferences and the multiple ways that gender differences in preference for submissive sexual fantasies can be eliminated by easily assessed demographic and contextual differences in the experiences of women and men.

EU HTA Regulation and Joint Clinical Assessment-Threat or Opportunity?

The vision of a unified European HTA is by no means a new endeavor. At its core are the publicly declared ambitions to harmonize assessments of clinical data within the EU and avoid the duplication of efforts. Not surprisingly, these ambitions are publicly announced to be motivating the new 2022 EU HTA regulation. However, industry experts typically see more of a risk for additional bureaucracy resulting in delays, further scrutiny, and one additional EU (clinical) dossier to submit on top of all national HTA dossiers, which could be considered a duplication of effort and therefore counterproductive. Regardless of how the details of the process will be defined and how the entire process will work in practice, we can be sure that EU officials will refer to the EU HTA and Joint Clinical Assessment (JCA) in particular as a learning system. The purpose of this article is to take a closer look at the new EU HTA regulation and analyze threats and opportunities for manufacturers and what the resulting opportunities and threats will be at the affiliate level throughout the EU.

Designs of clinical swallowability assessments of solid oral dosage forms in regulatory submissions.

The swallowability of solid oral dosage forms (SODFs) is crucial for medication safety and adherence. Both regulatory agencies and sponsors are concerned with bringing swallowable SODFs to patients. However, no best practices are available for assessing swallowability. Therefore, we conducted a comparative analysis of clinical swallowability assessments (CSAs) for SODFs in regulatory submissions to identify current study design practices. CSAs were identified from a "swallowability" keyword search of a Food and Drug Administration database. Notable design trends among the 17 CSAs were not assessing swallowability as a primary endpoint (76 %); enrolling pediatric patients (76 %); administering assessments post-screening (76 %); and utilizing questionnaires (100 %). A design trend with near equal frequency (∼50 %) was single- or multiple-doses of product administration. Study subjects were the primary questionnaire respondents (82 %), usually using a Likert scale (92 %, 12/13). CSAs generally dichotomized the responses for analysis (65 %) without pre-specified threshold values (59 %). Overall, while study designs exhibited trends, methodology variations may impact swallowability measurements affecting the interpretation of results. Thus, developing robust and valid assessment tools for swallowability is imperative to produce clinically relevant data and inform regulatory decision-making. Collaboration between regulatory agencies and sponsors is warranted to create best practices and ensure high quality swallowability data.

Tickle fetishism: pleasure beyond playfulness.

Tickling is commonly perceived as juvenile play associated with laughter. However, its potential connection to adult sexual behavior has largely remained unexplored. Our online survey, primarily distributed among individuals interested in tickle fetishism, explored tickling and its association with sexual behavior. Ticklishness types, tools, preferred body parts, and partner preferences, were examined. Results revealed diverse patterns of ticklishness changes over time and distinct body-part preferences for different types of tickling. Childhood experiences and exposure to tickling content in television were found to shape individuals' affinity for tickle fetishism. A quarter of respondents reported experiencing orgasms exclusively from tickling, while around 88% expressed sexual satisfaction through tickling alone, indicating its sufficiency as a sexual stimulus among fetishists. Tickling desire decreased after orgasm, indicating an association between tickling and sexual activity. Moreover, ticklishness degree predicted preferences for being tickled rather than tickling others. Exploratory factor analysis identified three factors underlying tickling and sexual experiences: enjoyment and frequency of tickling during sexual activity; preference for intense sexual experiences; age of becoming sexually active. In conclusion, this study provides unique insights into tickling and its connections to sexual context, enhancing our understanding of diverse human sexual behavior and tickle fetishism as a distinct preference.

Data Submission: HOW the Power of One Creates the Power of Many.

This article is the third and final article in a series exploring the WHAT, WHY, and HOW of data collection and data utilization. The final step, the HOW of data submission, provides discussion and guidance in contributing your data to the collective voice, including submitting data from the school, district, state, and national levels. Submitting individual school nursing data enriches the bigger story and increases the awareness and meaningfulness of school health data, the role of the school nurse as an integral member of the school community, and the connections of student health and academic outcomes. This article will also explore how to submit your school health data and the opportunities to submit it to district, state, or national levels, including to the National School Health Data Set: Every Student Counts! (ESC!).

Interdisciplinary lessons and recommendations for the evaluation of replicability in behavioral sciences.

As the scientific community becomes aware of low replicability rates in the extant literature, peer-reviewed journals have begun implementing initiatives with the goal of improving replicability. Such initiatives center around various rules to which authors must adhere to demonstrate their engagement in best practices. Preliminary evidence in the psychological science literature demonstrates a degree of efficacy in these initiatives. With such efficacy in place, it would be advantageous for other fields of behavioral sciences to adopt similar measures. This letter provides a discussion on lessons learned from psychological science while similarly addressing the unique challenges of other sciences to adopt measures that would be most appropriate for their field. We offer broad considerations for peer-reviewed journals in their implementation of specific policies and recommend that governing bodies of science prioritize the funding of research that addresses these measures.

Navigating Institutional Review Boards.

Obtaining institutional review board (IRB) approval can be an overwhelming task, especially for new researchers. IRB approval can require many documents and steps. It is important to start the submission early, have patience throughout the process, and determine what can help expedite the process. Research cannot begin without IRB approval, which is necessary when working with human subjects. Ultimately, the researchers and IRB have the same goal of enabling good research with minimal subject risk. The goal of this article is to give an overview of the IRB for practitioners performing research in podiatric medicine and surgery.

Developing and Validating a Model of Humeral Stem Primary Stability, Intended for In Silico Clinical Trials.

In silico clinical trials (ISCT) can contribute to demonstrating a device's performance via credible computational models applied on virtual cohorts. Our purpose was to establish the credibility of a model for assessing the risk of humeral stem loosening in total shoulder arthroplasty, based on a twofold validation scheme involving both benchtop and clinical validation activities, for ISCT applications. A finite element model computing bone-implant micromotion (benchtop model) was quantitatively compared to a bone foam micromotion test (benchtop comparator) to ensure that the physics of the system was captured correctly. The model was expanded to a population-based approach (clinical model) and qualitatively evaluated based on its ability to replicate findings from a published clinical study (clinical comparator), namely that grit-blasted stems are at a significantly higher risk of loosening than porous-coated stems, to ensure that clinical performance of the stem can be predicted appropriately. Model form sensitivities pertaining to surgical variation and implant design were evaluated. The model replicated benchtop micromotion measurements (52.1 ± 4.3 µm), without a significant impact of the press-fit ("Press-fit": 54.0 ± 8.5 µm, "No press-fit": 56.0 ± 12.0 µm). Applied to a virtual population, the grit-blasted stems (227 ± 78µm) experienced significantly larger micromotions than porous-coated stems (162 ± 69µm), in accordance with the findings of the clinical comparator. This work provides a concrete example for evaluating the credibility of an ISCT study. By validating the modeling approach against both benchtop and clinical data, model credibility is established for an ISCT application aiming to enrich clinical data in a regulatory submission.

Patterns in assignment submission times: Analysis of factors contributing to undergraduate students' commitment to core-curriculum related course.

Co-curricular activities equip students with essential skills and knowledge for personal and professional growth. Despite their importance, many students exert minimal effort to complete the assigned tasks. Instructors perceive that the lack of emphasis on final exams in co-curricular subjects reduces student effort and commitment. Moreover, poor time management and lack of effort in completing tasks have increased across various subjects in recent years. Therefore, it is important to investigate the factors that contribute to student commitment towards co-curricular subjects. In this study, the submission status of 339 tasks was retrieved from the student learning system to measure student commitment based on whether tasks were submitted on time, delayed, or not submitted. A chi-square test f was used to investigate the relationship between students' demographic characteristics and their commitment. The findings revealed a significant association between student commitment and the type of task given (p < 0.001). Students were more likely to submit presentations on time compared to written assignments. Projects were more likely to be delayed, while written assignments had a high frequency of no submission. Age was a significant predictor of commitment (p < 0.05), with students over 20 more likely to submit on time and students under 20 more likely to ignore submission. Gender was also a significant predictor of commitment (p < 0.001), with female students having a higher percentage and frequency of on-time submissions while male students having a higher number of no submissions. However, no significant association was found between the study year and commitment (p > 0.05), indicating that the year of the study could not determine the level of commitment to the course. Overall, these findings could be used to guide the preparation of tasks and assignments in co-curricular subjects to enhance student commitment and holistic development.

Editorial viewpoints of scientific publishing for early-career research scientists.

While the structure and composition of the scientific manuscript is well known within scientific communities, insider knowledge such as the tricks of the trade and editorial viewpoints of scientific publishing are often less known to early-career research scientists. This article focuses on the key aspects of scientific publishing, including tips for success geared towards senior postdocs and junior faculty. It also highlights important considerations for getting manuscripts published in an efficient and successful manner.

Asia Core Dossier: Standardizing CMC Requirement to Facilitate Best Case Submissions in Asia.

When the regulatory requirements are converged or harmonized, the country-specific variance of countries is often reduced or omitted, and this facilitates the possibility of preparing a core dossier that caters to multiple countries. When such options of a core dossier are acceptable to multiple countries, the resource required to prepare the dossier and the time taken to prepare it is also reduced, thus eliminating resource constraints in supporting dossier planning and preparation and indirectly facilitating earlier submission in countries. In this paper, the authors have illustrated a process applied to standardize the dossier requirements amongst selected countries in Asia, producing an output of a core dossier that applies to four submission types amongst these countries. The core dossier adopts the International Council for Harmonization-Common Technical Dossier format as a reference. Main focus is the standardization of format and requirements within the Module 3 or Chemistry Manufacturing Controls sections of the dossier, which from the authors' organizational experience usually notes a higher variances and country-specific elements. Development of the dossier standardization process is due to an internal hurdle within the authors' organization, where global resource constraints and prioritizations of dossier preparation and compliance review process needed to be improved to facilitate earlier or near-simultaneously submissions in the majority of the Asia countries. The paper demonstrates an assessment of the dossier components and standardization to assemble a fit-for-purpose core dossier termed 'Asia Core Dossier' (ACD). ACD has been successfully implemented within the authors' organization to reduce country-specific requirements and facilitate earlier (fit for strategy) submissions in the selected Asia countries. The paper also discusses the tangible benefits of the authors' experiences from utilizing the ACD. Regulatory professionals in different organizations could reference the ACD as a template for preparing a simplified and efficient dossier and as a relevant component of Good Submission Practice (GSubP).

Factor Analysis With Unusual Sexual Interests: A Replication Study in a Representative Population Sample.

A previous study found a variety of unusual sexual interests to cluster in a five-factor structure, namely submission/masochism, forbidden sexual activities, dominance/sadism, mysophilia, and fetishism (Schippers et al., 2021). The current study was an empirical replication to examine whether these findings generalized to a representative population sample. An online, anonymous sample (N = 256) representative of the Dutch adult male population rated 32 unusual sexual interests on a scale from 1 (very unappealing) to 7 (very appealing). An exploratory factor analysis assessed whether similar factors would emerge as in the original study. A subsequent confirmatory factor analysis served to confirm the factor structure. Four slightly different factors of sexual interest were found: extreme, illegal and mysophilic sexual activities; light BDSM without real pain or suffering; heavy BDSM that may include pain or suffering; and illegal but lower-sentenced and fetishistic sexual activities. The model fit was acceptable. The representative replication sample was more sexually conservative and showed less sexual engagement than the original convenience sample. On a fundamental level, sexual interest in light BDSM activities and extreme, forbidden, and mysophilic activities seem to be relatively separate constructs.

Pro-active drug-facilitated crimes (DFC): a study in the Department of Forensic Medicine of Paris, France.

INTRODUCTION: Proactive drug facilitated crime (DFC) is the administration of psychoactive substances (PAS) for criminal purposes without the victim's knowledge or by force. In Paris, France, patients who report suspected proactive DFC to the police are examined at the Department of Forensic Medicine (DFM) of the Hôtel-Dieu Hospital. Preventively blood and urine samples are collected but not systematically analyzed by the judicial authority. We aimed to assess the proportion of probable proactive DFC in patients examined at the Hôtel-Dieu DFM following a police report for suspected proactive DFC. METHOD: Blood and urine samples were collected from 100 patients. Toxicological analyses were performed by the toxicology laboratory of the Lariboisière Hospital. The results were correlated with the clinical data collected at the initial and follow-up consultations. RESULTS: At least one PAS was detected in 86% of the cases (voluntary or involuntary intake). After correlation with clinical data, 32% of the cases were classified as probable proactive DFC. In these cases, 49% of the substances identified were illicit substances (amphetamines, MDMA, etc.); 16% were benzodiazepines and related substances; 16% were antihistamines and sedatives; 14% were opioids; and 5% were antidepressants and anti-epileptics. In 90% of the cases, patients reported a voluntary ethanol consumption in the hours prior to the suspected proactive DFC. CONCLUSION: Toxicological analyses revealed a high proportion of both probable proactive DFC and probable opportunistic DFC. Our results indicate the need to perform systematical toxicological analysis in cases of suspected DFC.

Combining surface-enhanced Raman spectroscopy and paper spray mass spectrometry for the identification and confirmation of psychotropic substances in alcoholic beverages.

Criminal practices in which an individual becomes vulnerable and prone to sexual assault after ingesting drinks spiked with doping substances have become a social concern globally. As forensic protocols require a multi-tiered strategy for chemical evidentiary analysis, the backlog of evidence has become a significant problem in the community. Herein, a fast, sensible, and complementary dual analytical methodology was developed using a single commercial paper substrate for surface-enhanced Raman spectroscopy (SERS) and paper spray mass spectrometry (PS-MS) analysis to identify psychotropic substances added to alcoholic beverages irrefutably. To study and investigate this criminal practice, pharmaceutical formulations containing distinct psychotropic substances (zolpidem, clonazepam, diazepam, and ketamine) were added to drinks typically consumed at parties and festivals (Pilsen beer, açaí Catuaba®, gin tonic, and vodka mixed with Coca-Cola Zero®). A simple liquid-liquid extraction with a low-temperature partitioning (LLE-LTP) procedure was applied to the drinks and effectively minimized matrix effects. As a preliminary analysis, SERS spectra combined with Hierarchical Clustering Analysis (HCA) provided sufficient information to investigate the samples further. The presence of the protonated species for the psychotropic substances in the spiked drinks was readily verified in the mass spectra and confirmed by tandem mass spectrometry. Finally, the results demonstrate the potential of this methodology to be easily implemented into the routine of forensic laboratories and to be further employed at harm reduction tends at parties and festivals to detect contaminated beverages promptly and irrefutably as an efficient tool to prevent such crimes.

DNA sequences from type specimens and type strains - how to increase their number and improve their annotation in NCBI GenBank and related databases.

Scientific names permit humans and search engines to access knowledge about the biodiversity that surrounds us, and names linked to DNA sequences are playing an ever-greater role in search-and-match identification procedures. Here, we analyze how users and curators of the National Center for Biotechnology Information (NCBI) are flagging and curating sequences derived from nomenclatural type material, which is the only way to improve the quality of DNA-based identification in the long run. For prokaryotes, 18,281 genome assemblies from type strains have been curated by NCBI staff and improve the quality of prokaryote naming. For Fungi, type-derived sequences representing over 21,000 species are now essential for fungus naming and identification. For the remaining eukaryotes, however, the numbers of sequences identifiable as type-derived are minuscule, representing only 1,000 species of arthropods, 8,441 vertebrates, and 430 embryophytes. An increase in the production and curation of such sequences will come from (i) sequencing of types or topotypic specimens in museum collections, (ii) the March 2023 rule changes at the International Nucleotide Sequence Database Collaboration requiring more metadata for specimens, and (iii) efforts by data submitters to facilitate curation, including informing NCBI curators about a specimen's type status. We illustrate different type-data submission journeys and provide best-practice examples from a range of organisms. Expanding the number of type-derived sequences in DNA databases, especially of eukaryotes, is crucial for capturing, documenting, and protecting biodiversity.

Longitudinal qualitative study of paired mentor-mentee perspectives on the abstract submission process.

BACKGROUND: Submitting research abstracts to scientific societies is expected in academic medicine and requires dedicated time and effort. The authors queried mentors and mentees to ascertain what topics and proposed strategies should be included in a new curriculum to enhance the abstract submission process. METHODS: Between May 2019 and March 2020, the authors enrolled 14 senior-rank mentors from diverse disciplines at a tertiary musculoskeletal center and their 14-paired mentees (mostly residents and fellows) into a several-component qualitative study consisting of in-depth interviews several months before abstract submission addressing prior experiences, and longitudinal follow-up interviews 1 month before, 1 week before, and 1 week after submission to uncover challenges faced during the actual process and strategies that were effective in overcoming these challenges. Additional contacts occurred through November 2020 to ascertain outcomes of submissions. Mentors and mentees were unaware of each other's responses. Responses were grouped into categories using grounded theory and a comparative analytic strategy. RESULTS: At enrollment participants recounted details from prior abstracts that included experiences with the submission process such as format, content, and online requirements, and experiences with interpersonal interactions such as managing coinvestigators' competing priories and consulting with statisticians in a timely manner. Benefits of submitting abstracts included advancing mentees' careers and increasing research methodology rigor. Challenges encountered during the submission process included meeting deadlines before all data were acquired, time away from other responsibilities, and uncertainty about handling changing conclusions as more data accrued. Delayed feedback from coinvestigators and broadening the scope or changing the focus of the abstract compounded the time crunch to meet the submission deadline. At the time of abstract submission mentor-mentee pairs agreed that major challenges were dealing with collaborators, incomplete data/limited results, and different work styles. The authors developed a proposal for a comprehensive curriculum to include organizational, technical and interpersonal topics. CONCLUSIONS: This longitudinal qualitative study involving mentor-mentee pairs revealed multiple benefits and challenges associated with submitting research abstracts. These findings provide the foundation for a comprehensive curriculum to enhance this recurring labor-intensive undertaking and cornerstone of academic medicine.