bluuebunny/crossref_metadata_2025 huggingface dataset:
Managerialism at the United Nations
Authors: Grover Leena
Published: January 2024

One of the most significant developments in the field of transitional justice is the shift from national to international content creation regarding what constitutes a transitional injustice and how to address it. This is the story about that shift, how the United Nations (UN) went from observing to supporting and then managing transitional justice efforts. This chapter is divided into four parts. First, the UN’s initial observation of and support for national transitional justice efforts is summarized. Second, the shift from national to international content creation in this field is traced. It is argued that the UN achieved this shift through a combination of four techniques: blurring the distinction between hard and soft international laws; thickening these international norms; asserting the hegemony of these norms; and assuming the authority to administer them. Third, injustices marginalized by the UN’s transitional justice regime are fleshed out. It is argued that the UN’s understanding of transitional justice excludes four overlapping categories of injustices in transitioning societies: distributive injustices; systemic injustices; “ordinary” criminal injustices; and transitional injustices addressed through “ordinary” laws or politics. Finally, it is demonstrated that, while significantly increasing its management of transitions, the UN has nevertheless maintained a narrow and historically contingent understanding of transitional justice. This combination of administrative expansion and regime stability has been possible through the UN’s creation of distinct conceptual baskets that neighbor transitional justice—rule of law, non-recurrence, and addressing the root causes of conflict—and allocating interventions in transitioning societies to them.
Same-Sex Couples under the International Right to Marry
Authors: Waaldijk Kees
Published: January 2024

This analysis of the textual history of the international human right to marry, and of the international case law on same-sex marriage, argues that this right does not exclude same-sex couples. The words ‘men and women’ in this right were not inserted to codify heterosexual exclusivity, but to emphasize equality of women and men. Several international human rights bodies now consider this gender-neutral right applicable to same-sex couples, but still allow countries (at least for some transitional period) to keep excluding them from marriage. With the growing number of countries opening up marriage, and with the increased focus on non-discrimination on grounds of sexual orientation, two trends in international law have emerged: to require some alternative recognition when same-sex couples are excluded from marriage (e.g. cohabitation rights or registered partnership), and to require recognition of existing same-sex marriages (including foreign marriages, and marriages where a transgender spouse changes legal gender).
Population comparative genomics discovers gene gain and loss during grapevine domestication
Authors: Long Qiming , Cao Shuo , Huang Guizhou , Wang Xu , Liu Zhongjie , Liu Wenwen , Wang Yiwen , Xiao Hua , Peng Yanling , Zhou Yongfeng
Published: January 2024

Plant domestication are evolutionary experiments conducted by early farmers since thousands years ago, during which the crop wild progenitors are artificially selected for desired agronomic traits along with dramatic genomic variation in the course of moderate to severe bottlenecks. However, previous investigations are mainly focused on small-effect variants, while changes in gene contents are rarely investigated due to the lack of population-level assemblies for both the crop and its wild relatives. Here, we applied comparative genomic analyses to discover gene gain and loss during grapevine domestication using long-read assemblies of representative population samples for both domesticated grapevines (V. vinifera ssp. vinifera) and their wild progenitors (V. vinifera ssp. sylvestris). Only ∼7% of gene families were shared by 16 Vitis genomes while ∼8% of gene families were specific to each accession, suggesting dramatic variations of gene contents in grapevine genomes. Compared to wild progenitors, the domesticated accessions exhibited an increased presence of genes associated with asexual reproduction, while the wild progenitors showcased a higher abundance of genes related to pollination, revealing the transition from sexual reproduction to clonal propagation during domestication processes. Moreover, the domesticated accessions harbored fewer disease-resistance genes than wild progenitors. The SVs occurred frequently in aroma and disease-resistance related genes between domesticated grapevines and wild progenitors, indicating the rapid diversification of these genes during domestication. Our study provides insights and resources for biological studies and breeding programs in grapevine.
Affective neuroscience: applications for sexual medicine research and clinical practice
Authors: Mills-Finnerty Colleen , Staggs Halee , Bittoni Celeste , Wise Nan
Published: January 2024

Introduction

Affective neuroscience is the study of the brain substrates of emotional, embodied experiences. Affective neuroscience theory (ANT) is based on experimental evidence that all mammals are hardwired with 7 primary subcortical emotional operating systems, or “core emotions,” that have overlapping but distinct circuits buried in the deep, ancient parts of the brain. Imbalances in the 7 core emotions can affect multiple aspects of the individual’s psychosocial well-being (eg, depression, anxiety, substance abuse). Here, we propose that core emotions can also influence sexual function and, specifically, that imbalances in core emotions are the bridge connecting psychiatric symptoms (eg, anhedonia) to sexual dysfunction (eg, anorgasmia).

Objectives

In this targeted review and commentary, we outline potential connections between ANT and sexual medicine research and clinical practice. We summarize ANT by defining the 3-level BrainMind and core emotions; examining how they relate to personality, behavior, and mental health; and determining the implications for sexual health research and clinical practice.

Methods

A targeted literature review was conducted. Case studies were adapted from client files and clinician interviews and then anonymized.

Results

We propose a novel organizational schema for implementing affective balance therapies for sexual dysfunction, which integrate psychoeducational, somatic, and cognitive therapeutic approaches under the ANT framework. We provide 3 patient case studies (anorgasmia, hypersexuality, spinal cord injury) outlining the implementation of this approach and patient outcomes.

Conclusion

ANT has practical translational applications in sexual health research and clinical practice. By integrating our understanding of the role of core emotions in human sexuality, clinicians can better tailor treatments to address sexual dysfunction.
Facial Anthropometric Analysis of Gender-Related Characteristics in Computed Tomography
Authors: Luo Guan-Jie , Chou Pang-Yun , Chen Chih-Hao
Published: January 2024

Background

In recent years, facial feminization surgery (FFS) has gained increasing popularity because of increases in transgender individuals and the acceptance of diversity in gender identity. However, there is still a scarcity of anthropometric research to guide evidence-based practices for FFS in Taiwan.

Aim and Objectives

The purpose of this study was to provide a reference for surgeons to achieve optimal outcomes for patients undergoing FFS. The anthropometric analysis could help surgeons meet patients' specific requirements and improve patients' alignment with their gender identity.

Materials and Methods

The study group consisted of 100 patients (50 males and 50 females) who had undergone cranial computed tomography at Chang Gung Memorial Hospital in Taiwan because of the indication of blunt injuries to the head and face with suspected skull and facial fractures. The computed tomography images were imported into the OsiriX image software to conduct an anthropometric evaluation. The parameters used in the measurements included 2 aspects: bone and soft tissue anthropometric analysis.

Results

Anthropometric data were obtained from 50 males (age 32.6 ± 11.4 years) and 50 females (age 33.7 ± 10.3 years). The results for bone measurements showed that both the forehead bossing length and nasal bone width in the male group were significantly greater. The frontal angle in both bone and soft tissue in the male group was significantly smaller. The chin height and bigonial width in both bone and soft tissue in the male group were significantly greater. Although the average gonial angle was greater in the female group, the difference was not significant. For the measurements of lip projection, the results showed that there was no significant difference. Although this group of Asian males had more acute nasolabial angles, the difference was not statistically significant. However, the average nasofrontal angle among females was significantly more obtuse than among males.

Conclusion

The results revealed that Asian males tend to have more prominent superior orbital rims, wider nasal bones, and wider and taller mandibles compared with Asian females. Despite showing some trends, the gonial angle and lip projections did not reveal any significant differences, which is likely because of a large amount of variation.
Platelet-Rich Plasma Lysate Enhances the Osteogenic Differentiation of Adipose-Derived Stem Cells
Authors: Chen Chia-Fang , Wang Po-Fang , Liao Han-Tsung
Published: January 2024

Adipose-derived stem cells (ADSCs) have become an accepted source of cells in bone tissue engineering. This study aimed to investigate whether platelet-rich plasma (PRP) lysate can replace traditional fetal bovine serum as a culture medium with the enhanced proliferation and osteogenic potential of ADSCs. We divided the experiment into 5 groups where the ADSCs were cultured in an osteogenic medium containing 2.5%, 5%, 7.5%, and 10% PRP lysate with 10% fetal bovine serum as the control group. The cell proliferation, alkaline phosphatase (ALP) activity, ALP stain, alizarin red stain, osteocalcin (OCN) protein expression, and osteogenic-specific gene expression were analyzed and compared among these groups. The outcome showed that all PRP lysate–treated groups had good ALP stain and ALP activity performance. Better alizarin red stains were found in the 2.5%, 5%, and 7.5% PRP lysate groups. The 2.5% and 5% PRP lysate groups showed superior results in OCN quantitative polymerase chain reaction, whereas the 5% and 7.5% PRP lysate groups showed higher OCN protein expressions. Early RUNX2 (Runt-related transcription factor 2 () genes were the most expressed in the 5% PRP lysate group, followed by the 2.5% PRP lysate group, and then the 7.5% PRP lysate group. Thus, we concluded that 5% PRP lysate seemed to provide the optimal effect on enhancing the osteogenic potential of ADSCs. Platelet-rich plasma lysate–treated ADSCs were considered to be a good cell source for application in treating nonunion or bone defects in the future.
Evaluation of Concomitant Facial Fracture in Traumatic Brain Injury Patients—Simplification and External Validation of a Prediction Model
Authors: Lin Jennifer An-Jou , Li Pei-Hua , Liao Chien-Hung , Hsieh Chi-Hsun , Kuo Yu-Chi , Hsu Ting-An , Chu Yu-Ying , Fu Chih-Yuan
Published: January 2024

Background

Patients with traumatic brain injuries (TBIs) often experience concurrent facial bone fractures. In 2021, a prediction model with 10 variables was published and precisely predicted concomitant facial fractures in TBI patients. Herein, external validation and simplification of this model was performed.

Methods

Traumatic brain injury patients treated at a major referral trauma center were retrospectively reviewed for 1 year. The original prediction model (published in 2021), which was developed from a rural level II trauma center, was applied for external validation. A new and simplified model from our level I trauma center was developed and backwardly validated by rural level II trauma center data.

Results

In total, 313 TBI patients were enrolled; 101 (32.3%) had concomitant facial fractures. When the previous prediction model was applied to the validation cohort, it achieved acceptable discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.713 and good precision, with a Brier score of 0.083. A new and simplified model with 6 variables (age, tooth rupture, epistaxis, facial lesion, eye injury, and intracranial hemorrhage) was created with excellent discrimination (AUC = 0.836) and good precision (Brier score of 0.055). The backward validation of this new model also showed excellent discrimination in the cohort used to develop the original model (AUC = 0.875).

Conclusion

The original model provides an acceptable and reproducible prediction of concomitant facial fractures among TBI patients. A simplified model with fewer variables and the same accuracy could be applied in the emergency department and at higher- and lower-level trauma centers.
Comparing Surgical Site Infection Rate Between Primary Closure and Rhomboid Flap After Stoma Reversal
Authors: Chu Che-Ming , Chen Chih-Cheng , Chang Yu-Yao , Syu Kai-Jyun , Lin Shih-Lung
Published: January 2024

Background

Primary closure (PC) is a common wound closure procedure after stoma reversal and is associated with a high rate of surgical site infection (SSI). This study introduced a new method of skin closure, a rhomboid flap (RF), for skin closure after stoma reversal and compared the SSI rate between the 2 techniques.

Methods

This is a single-center retrospective study. Patients who underwent colostomy or ileostomy closure performed using either rotation flap (n = 33) or PC (n = 121) techniques for skin closure after stoma reversal between April 2019 and July 2022 were enrolled in this study. Medical records were retrospectively reviewed to obtain data. Both groups were followed up postoperatively at 1 month for wound infection. Wound infection within 30 days after surgery was indicated by the presence of purulent discharge, erythema, local heat, or positive culture for bacteria.

Results

In the PC group, the infection rate was 25.6% (n = 121) compared with 12.1% (n = 33) in the RF group (P = 0.158). Among the patients who underwent colostomy reversal, the infection rate of the RF group was significantly lower compared with that of the PC group (11.1% vs 36.9%, P = 0.045). Among the patients who underwent ileostomy reversal, no significant differences in the infection rates between the groups were found (13.3% vs 12.5%, P = 1.000).

Conclusions

Although the RF technique requires slightly longer operative time for flap design in practice than the linear closure method, the technique can significantly reduce the SSI rate after colostomy reversal through the dissection of the surrounding inflammatory tissues and obliteration of the dead space. Additional studies are required to evaluate this technique, compare it with other existing methods, and explore long-term complications.
Chang Gung Forum
Authors: Chen Gloria , Tu Junior Chun-Yu , Chuang Kai-Ti , Wang Po-Fang , Yao Chuan-Fong , Chou Pang-Yun , Lu Ting-Chen , Chen Ying-An , Chang Chun-Shin , Lin Clement Cheng-Hui , Chen Zung-Chung , Lo Lun-Jou , Chen Yu-Ray
Published: January 2024

Introduction

The Chang Gung Forum has been dedicated to the care of craniofacial anomalies since 2000. This annual continuing medical education program focuses on orofacial cleft and surgery-first orthognathic surgery by providing up-to-date information and management guidelines. This study explored how the Chang Gung Forum has influenced medical perspectives, decisions, and practices in a multidisciplinary craniofacial team.

Methods

Between 2000 and 2022, 20 Chang Gung Forums have been held. A questionnaire was distributed among 170 attendees who had participated in the forum more than once. The questionnaire collected information on the participants' experiences and levels of satisfaction with the educational program and whether or how it had influenced their clinical practice.

Results

Valid responses from 86 attendees (response rate, 50.6%) who had participated more than once were collected and analyzed. The overall satisfaction rate of the Chang Gung Forum based on the respondents' most recent visits was 4.28 ± 0.63 out of 5. Of the respondents, 90.9% acknowledged changes in their clinical practice, with modifications in surgery plans and decisions being the most notable (48.5%). In addition, comprehension increased throughout years of attending the annual forum (P < 0.001).

Conclusion

The Chang Gung Forum has contributed markedly to the community of congenital craniofacial anomalies. The program will continue providing updated information and influencing the clinical decision-making of health care professionals.
Enhanced Diabetic Rat Wound Healing by Platelet-Rich Plasma Adhesion Zwitterionic Hydrogel
Authors: Huang Nan-Chieh , Huang Nien-Chi , Kang Lan-Ya , Hsieh Pai-Shan , Dai Lien-Guo , Dai Niann-Tzyy , Huang Chun-Jen
Published: January 2024

Background

The skin is the largest organ in the human body and serves as a barrier for protective, immune, and sensory functions. Continuous and permanent exposure to the external environment results in different levels of skin and extracellular matrix damage. During skin wound healing, the use of good dressings and addition of growth factors to the wound site can effectively modulate the rate of wound healing. A dressing containing bioactive substances can absorb wound exudates and reduce adhesion between the wound and dressing, whereas growth factors, cytokines, and signaling factors can promote cell motility and proliferation.

Aim and Objectives

We prepared a functional wound dressing by combining platelet-rich plasma (PRP) and zwitterionic hydrogels. Functional wound dressings are rich in various naturally occurring growth factors that can effectively promote the healing process in various types of tissues and absorb wound exudates to reduce adhesion between wounds and dressings. Furthermore, PRP-incorporated zwitterionic hydrogels have been used to repair full-thickness wounds in Sprague-Dawley rats with diabetes (DM SD).

Materials and Methods

Fibroblasts and keratinocytes were cultured with PRP, zwitterionic hydrogels, and PRP-incorporated zwitterionic hydrogels to assess cell proliferation and specific gene expression. Furthermore, PRP-incorporated zwitterionic hydrogels were used to repair full-thickness skin defects in DM SD rats.

Results

The swelling ratio of hydrogel, hydrogel + PRP1000 (108 platelets/mL), and hydrogel + PRP1000 (109 platelets/mL) groups were similar (~07.71% ± 1.396%, 700.17% ± 1.901%, 687.48% ± 4.661%, respectively) at 144 hours. The tensile strength and Young modulus of the hydrogel and hydrogel + PRP10000 groups were not significantly different. High concentrations of PRP (approximately 108 and 109 platelets/mL) effectively promoted the proliferation of fibroblasts and keratinocytes. The zwitterionic hydrogels were not cytotoxic to any cell type. High PRP concentration-incorporated zwitterionic hydrogels increased the rate of cell proliferation and significantly increased the expression of characteristic genes such as collagen, fibronectin, involucrin, and keratin. Subsequently, zwitterionic hydrogels with high PRP concentrations were used to repair full-thickness skin defects in DM SD rats, and a wound healing rate of more than 90% was recorded on day 12.

Conclusions

PRP contains high concentrations of growth factors that promote cell viability, enhance specific gene expression, and have a high medical value in cell therapy. Zwitterionic hydrogels have a 3-dimensional interconnected microporous structure and can resist cell adhesion without causing cytotoxicity. Platelet-rich plasma–incorporated zwitterionic hydrogels further enhance the cellular properties and provide an effective therapeutic option for wound healing.
It's Not a Spider Bite—It's MRSA!
Authors: Scordo Kristine Anne
Published: January 2024

Although there is an increased awareness of community-acquired methicillin-resistant Staphylococcus aureus (MRSA), there remains a bias of the public and health-care workers to blame spiders as a cause of skin and soft tissue infection when there is no valid incriminated evidence for this assumption. MRSA is a formidable infection and remains a threat to human health. Recognition and proper treatment by practitioners remain of utmost importance to improve patient outcomes.
Finger Thoracostomy for Tension Pneumothorax
Authors: Smith Tony , Wilbeck Jennifer
Published: January 2024

One of the injuries associated with chest trauma is pneumothorax, a condition where air accumulates between the parietal and visceral pleura in the chest leading to collapse of the lung due to pressure. Left untreated, a tension pneumothorax may develop leading to cardiovascular collapse. This article reviews the development of a tension pneumothorax, discusses the clinical recognition of the diagnosis, and outlines the procedure for performing a finger (or simple) thoracostomy. A simple mnemonic for the procedure is offered as a memory aid to reduce cognitive load for this procedure.
Feasibility and preliminary efficacy of an online mindful walking intervention among COVID-19 long haulers: A mixed method study including daily diary surveys
Authors: Aggarwal Abhishek , Qiao Shan , Yang Chih-Hsiang , Taylor Slone , Tam Cheuk Chi , Li Xiaoming
Published: January 2024

Objective

Mindful-walking (MW) intervention could be an effective strategy to address the psychosocial stressors and physical health challenges faced by COVID-19 long haulers. This study aims to test the feasibility of digitally delivering MW intervention among long haulers via social media and assess its preliminary efficacy on enhancing physical and psychosocial wellbeing.

Method

We recruited 23 participants via Facebook groups in March and November 2021 for a 4-week online MW intervention, consisting of mindfulness practices (2 sessions per week), delivered entirely through the Facebook group. The intervention was assessed using mixed methods. Quantitative data were collected through 28-day brief daily evening surveys over the 4 weeks intervention period, including affect, cognition, mindfulness, physical activity, and MW engagement. Qualitative data were extracted from Paradata (i.e., participants’ responses to the social media posts). Multilevel modeling was employed for statistical analysis and a pragmatic approach was used for qualitative analysis.

Results

The mean feasibility score was 4.93/7 (SD=1.88). Multilevel models showed that MW uptake on a given day was positively associated with positive affect (β=0.89,p<0.01), perceived cognition (β=0.52,p<0.05), and physical activity levels (β=0.41,p<0.05), and negatively associated with negative affect (β=-0.83,p<0.01). Total number of MW days across the study period were positively associated with mindfulness levels (β=0.3p<0.01). Paradata reported satisfaction in mindfulness skill enhancement, symptom management and well-being promotion.

Conclusion

The digital delivery of our MW intervention via Facebook showed high acceptability. Preliminary efficacy findings indicate improved mental wellbeing and physical activity among long haulers.
Phylogenetic tree statistics: a systematic overview using the new R package ‘treestats’
Authors: Janzen Thijs , Etienne Rampal S.
Published: January 2024

Phylogenetic trees are believed to contain a wealth of information on diversification processes. Comparing phylogenetic trees is not straightforward due to their high dimensionality. Researchers have therefore defined a wide range of one-dimensional summary statistics. However, it remains unexplored to what extent these summary statistics cover the same underlying information and what summary statistics best explain observed variation across phylogenies. Furthermore, a large subset of available summary statistics focusses on measuring the topological features of a phylogenetic tree, but are often only explored at the extreme edge cases of the fully balanced or unbalanced tree and not for trees of intermediate balance.

Here, we introduce a new R package that provides speed optimized code to compute 54 summary statistics. We study correlations between summary statistics on empirical trees and on trees simulated using several diversification models. Furthermore, we introduce an algorithm to create intermediately balanced trees in a well-defined manner, in order to explore variation in summary statistics across a balance gradient.

We find that almost all summary statistics are correlated with tree size, and it is difficult if not impossible to correct for tree size, unless the tree generating model is known. Furthermore, we find that across empirical and simulated trees, at least two large clusters of correlated summary statistics can be found, where statistics group together based on information used (topology or branching times). However, the finer grained correlation structure appears to depend strongly on either the taxonomic group studied (in empirical studies) or the diversification model (in simulation studies). Nevertheless, we can identify multiple groups of summary statistics that are strongly and consistently correlated, indicating that these statistics measure the same underlying property of a tree. Lastly, we find that almost all topological summary statistics vary non-linearly and sometimes even non-monotonically with our intuitive balance gradient.

Therefore, in order to avoid introducing biases and missing underlying information, we advocate for selecting as many summary statistics as possible in phylogenetic analyses. With the introduction of the treestats package, which provides fast and reliable calculations, such an approach is now routinely possible.
They all rock: A systematic comparison of conformational movements in LeuT-fold transporters
Authors: Licht Jacob A. , Berry Samuel P. , Gutierrez Michael A. , Gaudet Rachelle
Published: January 2024

Many membrane transporters share the LeuT fold—two five-helix repeats inverted across the membrane plane. Despite hundreds of structures, whether distinct conformational mechanisms are supported by the LeuT fold has not been systematically determined. After annotating published LeuT-fold structures, we analyzed distance difference matrices (DDMs) for nine proteins with multiple available conformations. We identified rigid bodies and relative movements of transmembrane helices (TMs) during distinct steps of the transport cycle. In all transporters the bundle (first two TMs of each repeat) rotates relative to the hash (third and fourth TMs). Motions of the arms (fifth TM) to close or open the intracellular and outer vestibules are common, as is a TM1a swing, with notable variations in the opening-closing motions of the outer vestibule. Our analyses suggest that LeuT-fold transporters layer distinct motions on a common bundle-hash rock and demonstrate that systematic analyses can provide new insights into large structural datasets.
scATAcat: Cell-type annotation for scATAC-seq data
Authors: Altay Aybuge , Vingron Martin
Published: January 2024

Cells whose accessibility landscape has been profiled with scATAC-seq cannot readily be annotated to a particular cell type. In fact, annotating cell-types in scATAC-seq data is a challenging task since, unlike in scRNA-seq data, we lack knowledge of “marker regions” which could be used for cell-type annotation. Current annotation methods typically translate accessibility to expression space and rely on gene expression patterns. We propose a novel approach, scATAcat, that leverages characterized bulk ATAC-seq data as prototypes to annotate scATAC-seq data. To mitigate the inherent sparsity of single-cell data, we aggregate cells that belong to the same cluster and create pseudobulk. To demonstrate the feasibility of our approach we collected a number of datasets with respective annotations to quantify the results and evaluate performance for scATAcat. scATAcat is available as a python package athttps://github.com/aybugealtay/scATAcat.
Viral antigen mismatch affects antiviral T-cell response and may impair immunotherapeutic efficacy against ATL
Authors: Sugata Kenji , Takatori Mitsuyoshi , Reda Omnia , Yang Tan Benjy Jek , Tokunaga Masahito , Sato Tomoo , Ueda Mitsuharu , Yamano Yoshihisa , Utsunomiya Atae , Satou Yorifumi
Published: January 2024

Human T-cell leukemia virus type 1 (HTLV-1) has the potential to transform primary CD4+T cellsin vitrowithin a short time; however, the majority of infected individuals maintain an asymptomatic and disease-free condition, suggesting the existence of an equilibrium between the proliferation of infected cells and host immunity. The decline in anti-viral immunity contributes to the transformation of the infected cells, leading to the development of adult T-cell leukemia/lymphoma (ATL). This study identified a variation in a major viral antigen, HTLV-1 Tax, in human leukocyte antigen-A24 (HLA-A24) positive individuals. Two variants of Tax301-309peptides, SFHNLHLLF (Tax301-309A) and SFHSLHLLF (Tax301-309B) were found to induce distinct T-cell immune responses in HLA-A24 positive individuals. There was a disparity between two Tax301-309peptides in the detection of anti-Tax301-309cytotoxic T-lymphocytes (CTLs) binding to A24/peptide multimers by flow cytometry analysis. More importantly, over half of the anti-Tax TCRs of anti-Tax CTLs from infected individuals did not recognize mismatched Tax301-309peptides by Enzyme-Linked Immunospot (ELISpot) assay using Jurkat T cells expressing the anti-Tax301-309specific TCR. These findings underscore the importance of matching the viral antigen epitope type in T-cell-based immunotherapy against ATL by using viral antigen Tax.

Key points

Epitope heterogeneity in the major viral antigen in HTLV-1 infection causes different T-cell responses in infected individuals.

Recommended guideline; performing virus typing to obtain optimal efficacy in T-cell-mediated immunotherapy against the viral antigen Tax
Comparative Analysis of Biomarkers in Type 2 Diabetes Patients with and without Comorbidities: Insights into the Role of Hypertension and Cardiovascular Disease
Authors: Savvopoulos Symeon , Hatzikirou Haralampos , Jelinek Herbert F.
Published: January 2024

Background

Type 2 diabetes mellitus (T2DM) are 90% of diabetes cases, and its prevalence and incidence, including comorbidities, are rising worldwide. Clinically, diabetes and associated comorbidities are identified by biochemical and physical characteristics including glycaemia, glycated hemoglobin (HbA1c), and tests for cardiovascular, eye and kidney disease.

Objectives

Diabetes may have a common etiology based on inflammation and oxidative stress that may provide additional information about disease progression and treatment options. Thus, identifying high-risk individuals can delay or prevent diabetes and its complications.

Design

In patients with or without hypertension and cardiovascular disease, as part of progression from no diabetes to T2DM, this research studied the changes in biomarkers between control and prediabetes, prediabetes to T2DM, and control to T2DM, and classified patients based on first-attendance data. Control patients and patients with hypertension, cardiovascular, and with both hypertension and cardiovascular diseases are 156, 148, 61, and 216, respectively.

Methods

Linear discriminant analysis is used for classification method and feature importance, This study examined the relationship between Humanin and mitochondrial protein (MOTSc), mitochondrial peptides associated with oxidative stress, diabetes progression, and associated complications.

Results

MOTSc, reduced glutathione and glutathione disulfide ratio (GSH/GSSG), interleukin-1β (IL-1β), and 8-isoprostane were significant (p<0.05) for the transition from prediabetes to T2DM, highlighting the importance of mitochondrial involvement. Complement component 5a (C5a) is a biomarker associated with disease progression and comorbidities, with GSH/GSSG, monocyte chemoattractant protein-1 (MCP-1), and 8-isoprostane being the most important biomarkers.

Conclusions

Comorbidities affect the hypothesized biomarkers as diabetes progresses. Mitochondrial oxidative stress indicators, coagulation, and inflammatory markers help assess diabetes disease development and provide appropriate medications. Future studies will examine longitudinal biomarker evolution.
Establishment of an easy-to-construct liver injury mouse model for longitudinal analysis by drinking-water administration of MDA
Authors: Iwasaka Takumi , Mizuno Tadahaya , Morita Katsuhisa , Azuma Iori , Nakagawa Tomoka , Nakashima Eri , Kusuhara Hiroyuki
Published: January 2024

Compound actions are diverse, capable of inducing various biological responses, making them a valuable exploratory tool for understanding biological mechanisms. While widely employed in liver dysfunction research, models requiring continuous administration for longitudinal studies come with high construction costs. Although drinking water models are useful, currently utilized compounds are limited, with thioacetamide being one of the few examples. Is it possible to expand drinking water models for liver dysfunction research? Addressing this question, our study focused on constructing a novel drinking water-induced liver injury model. Through data mining and literature research, 4,4’-methylenedianiline (MDA) was identified, whose drinking water administration consistently exhibited elevated ALT levels over 28 days. To evaluate differences in pathophysiological profiles compared to existing thioacetamide models, we acquired multi-view data of early biochemical test values, immune cell trafficking, and transcriptome over time. The analysis revealed unique features such as elevated total bilirubin in serum, increased monocyte-derived macrophages in the liver, and enhanced fibrinolysis in the liver, suggesting a model of cholestatic liver injury. This study proposes the first cholestatic liver injury model for compound drinking water administration, expanding the scope of longitudinal analysis in liver dysfunction research.
Learning predictive signatures of HLA type from T-cell repertoires
Authors: Ortega Maria Ruiz , Pogorelyy Mikhail V. , Minervina Anastasia A. , Thomas Paul G. , Walczak Aleksandra M. , Mora Thierry
Published: January 2024

T cells recognize a wide range of pathogens using surface receptors that interact directly with pep-tides presented on major histocompatibility complexes (MHC) encoded by the HLA loci in humans. Understanding the association between T cell receptors (TCR) and HLA alleles is an important step towards predicting TCR-antigen specificity from sequences. Here we analyze the TCR alpha and beta repertoires of large cohorts of HLA-typed donors to systematically infer such associations, by looking for overrepresentation of TCRs in individuals with a common allele.TCRs, associated with a specific HLA allele, exhibit sequence similarities that suggest prior antigen exposure. Immune repertoire sequencing has produced large numbers of datasets, however the HLA type of the corresponding donors is rarely available. Using our TCR-HLA associations, we trained a computational model to predict the HLA type of individuals from their TCR repertoire alone. We propose an iterative procedure to refine this model by using data from large cohorts of untyped individuals, by recursively typing them using the model itself. The resulting model shows good predictive performance, even for relatively rare HLA alleles.
SignalingProfiler2.0: a network-based approach to bridge multi-omics data to phenotypic hallmarks
Authors: Venafra Veronica , Sacco Francesca , Perfetto Livia
Published: January 2024

Unraveling the cellular signaling remodeling upon a perturbation is a fundamental challenge to understand disease mechanisms and to identify potential drug targets. In this pursuit, computational tools that generate mechanistic hypotheses from multi-omics data have invaluable potential. Here we presentSignalingProfiler2.0, a multi-step pipeline to systematically derive context-specific signaling models by integrating proteogenomic data with prior knowledge-causal networks. This is a freely accessible and flexible tool that incorporates statistical, footprint-based, and graph algorithms to accelerate the integration and interpretation of multi-omics data. Through benchmarking and rigorous parameter selection on a proof-of-concept study, performed in metformin-treated breast cancer cells, we demonstrate the tool’s ability to generate a hierarchical mechanistic network that recapitulates novel and known drug-perturbed signaling and phenotypic outcomes. In summary, SignalingProfiler2.0 addresses the emergent need to derive biologically relevant information from complex multi-omics data by extracting interpretable networks.
Hexose transporters CsHT3/16 involved in post-phloem transport and affected cucumber fruit development
Authors: Cheng Jintao , Wen Suying , Li Kexin , Zhou Yixuan , Zhu Mengtian , Neuhaus H. Ekkehard , Bie Zhilong
Published: January 2024

Hexoses are crucial for plant growth and fruit development. However, the role of hexose transporters in post-phloem sugar transport and maintenance of cellular sugar homeostasis in rapidly growing fruits, such as cucumber, is not yet fully understood. To clarify the impact of hexose transporters in cucumber fruits, we conducted systematic analyses of their tissue expression, localization, transport characteristics and physiological functions. The study revealed thatCsHT3,CsHT12 andCsHT16 are the primary hexose transporter genes expressed in cucumber fruit. During the ovary and young fruit stages,CsHT3 andCsHT16 were located in the SE/CC system, but as the cucumber fruit developed and expanded, both transporters shifted to phloem parenchyma cells. The knock-out mutants ofCsHT16display shorter fruits with a larger circumference, likely due to impaired homeostasis of sugars and hormones. Simultaneously reducing the expression ofCsHT3,CsHT12andCsHT16leads to decreased fruit size. Conversely, overexpression ofCsHT3results in increased fruit size and higher fruit sugar levels. Our data suggest thatCsHT16 plays an important role in maintaining sugar homeostasis to shape the fruit, whileCsHT3,CsHT12 andCsHT16 together determine the carbohydrates requirement of the enlarged cucumber fruit.
Repulsion from slow-diffusing nutrients improves chemotaxis towards moving sources
Authors: Bloxham Blox , Lee Hyunseok , Gore Jeff
Published: January 2024

Chemotaxis, or the following of chemical concentration gradients, is essential for microbes to locate nutrients. However, microbes often display paradoxical behaviors, such asEscherichia colibeing repelled by several amino acids. Here, we explore chemotaxis towards a moving source and demonstrate that when multiple nutrients are released from the source repulsion from certain nutrients actually improves chemotaxis towards the source. Because a moving source leaves most of the nutrient plume behind it, simply following the concentration gradient results in aiming behind the source and failing to intercept it. However, when attraction to a fast-diffusing nutrient and repulsion from a slow-diffusing nutrient are combined, motion in a new direction emerges and the chance of intercepting the source is increased up to six-fold. We demonstrate that this “differential strategy” is robust against numerous variations, including order-of-magnitude increases in the repellent release rate. Finally, we leverage existing data to show thatE. coliis attracted to fast-diffusing amino acids and repelled by slow-diffusing ones, suggesting it may utilize a differential strategy and providing an explanation for its repulsion from these amino acids. Our results thus illuminate new possibilities in how microbes can integrate signals from multiple gradients to accomplish the difficult chemotactic tasks.
Performance of GPT-4V(ision) in Ophthalmology: Use of Images in Clinical Questions
Authors: Tomita Kosei , Nishida Takashi , Kitaguchi Yoshiyuki , Miyake Masahiro , Kitazawa Koji
Published: January 2024

Background/aims

To compare the diagnostic accuracy of Generative Pre-trained Transformer with Vision (GPT)-4 and GPT-4 with Vision (GPT-4V) for clinical questions in ophthalmology.

Methods

The questions were collected from the “Diagnosis This” section on the American Academy of Ophthalmology website. We tested 580 questions and presented GPT-4V with the same questions under two conditions: 1) multimodal model, incorporating both the question text and associated images, and 2) text-only model. We then compared the difference in accuracy between the two conditions using the chi-square test. The percentage of general correct answers was also collected from the website.

Results

The GPT-4V model demonstrated higher accuracy with images (71.7%) than without images (66.7%, p<0.001). Both GPT-4 models showed higher accuracy than the general correct answers on the website [64.6 (95%CI, 62.9 to 66.3)].

Conclusions

The addition of information from images enhances the performance of GPT-4V in diagnosing clinical questions in ophthalmology. This suggests that integrating multimodal data could be crucial in developing more effective and reliable diagnostic tools in medical fields.

SYNOPSIS

The study compared the diagnostic accuracy of GPT-4 and GPT-4 with Vision for clinical questions in ophthalmology, finding that the performance improved when it analyzed both text and images.

WHAT IS ALREADY KNOWN ON THIS TOPIC

Text-based large language models (LLMs) have demonstrated significant potential in enhancing medical interpretation and diagnosis. Generative Pretrained Transformer 4 with Vision (GPT-4V) can address image-related questions, but the use of GPT-4V in ophthalmology has not yet been validated.

WHAT THIS STUDY ADDS

Our study reports the answer accuracy on ‘Diagnose This,’ provided by the American Academy of Ophthalmology, using GPT-4V. The integration of image data with GPT-4V enhances diagnostic accuracy in addressing ophthalmic clinical questions.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

Our study indicates that combining image data with GPT-4 can enhance diagnostic accuracy in ophthalmic clinical questions. The development of LLMs trained on medical-specific datasets could further increase accuracy, advancing towards practical clinical applications.
Limited genomic signatures of population collapse in the critically endangered black abalone (Haliotis cracherodii)
Authors: Wooldridge Brock , Orland Chloé , Enbody Erik , Escalona Merly , Mirchandani Cade , Corbett-Detig Russell , Kapp Joshua D. , Fletcher Nathaniel , Ammann Karah , Raimondi Peter , Shapiro Beth
Published: January 2024

The black abalone,Haliotis cracherodii, is a large, long-lived marine mollusc that inhabits rocky intertidal habitats along the coast of California and Mexico. In 1985, populations were impacted by a bacterial disease known as withering syndrome (WS) that wiped out >90% of individuals, leading to the species’ designation as critically endangered. Current conservation strategies include restoring diminished populations by translocating healthy individuals. However, population collapse on this scale may have dramatically lowered genetic diversity and strengthened geographic differentiation, making translocation-based recovery contentious. Additionally, the current prevalence of WS is unknown. To address these uncertainties, we sequenced and analyzed the genomes of 133 black abalone individuals from across their present range. We observed no spatial genetic structure among black abalone, with the exception of a single chromosomal inversion that increases in frequency with latitude. Genetic divergence between sites is minimal, and does not scale with either geographic distance or environmental dissimilarity. Genetic diversity appears uniformly high across the range. Despite this, however, demographic inference confirms a severe population bottleneck beginning around the time of WS onset, highlighting the temporal offset that may occur between a population collapse and its potential impact on genetic diversity. Finally, we find the bacterial agent of WS is equally present across the sampled range, but only in 10% of individuals. The lack of genetic structure, uniform diversity, and prevalence of WS bacteria indicates that translocation could be a valid and low-risk means of population restoration for black abalone species’ recovery.
DETECTION OF CELL ASSEMBLIES IN HIGH-DENSITY EXTRACELLULAR ELECTROPHYSIOLOGICAL RECORDINGS
Authors: Makdah Gabriel , Wiener Sidney I. , Pompili Marco N.
Published: January 2024

Cell assemblies, i.e., concurrently active groups of neurons, likely underlie neural processing for higher brain functions. Recent technological progress has enabled large-scale recording of neuronal activity, permitting the exploration and analysis of cell assembly dynamics. This review aims to provide both conceptual insights and practical knowledge pertaining to principal methodologies used for detecting cell assemblies in the last fifteen years. The goal is to assist readers in selecting and comparing various protocols to optimize their data processing and analysis pipeline. Each algorithm is explained with its fundamental principles, their application in neuroscience for cell assembly detection, and illustrated with published studies. Recognizing the similarities, advantages, and drawbacks of diverse methodologies may pave the way for developing new procedures for cell assembly identification to facilitate future endeavors in the understanding of brain activity.
Prolactin-mediates a lactation-induced suppression of arcuate kisspeptin neuronal activity necessary for lactational infertility in mice
Authors: Hackwell Eleni C.R. , Ladyman Sharon R. , Clarkson Jenny , McQuillan H. James , Boehm Ulrich , Herbison Allan E. , Brown Rosemary S.E. , Grattan David R.
Published: January 2024

The specific role that prolactin plays in lactational infertility, as distinct from other suckling or metabolic cues, remains unresolved. Here, deletion of the prolactin receptor (Prlr) from forebrain neurons or arcuate kisspeptin neurons resulted in failure to maintain normal lactation-induced suppression of estrous cycles. Kisspeptin immunoreactivity and pulsatile LH secretion were increased in these mice, even in the presence of ongoing suckling stimulation and lactation. GCaMP fibre photometry of arcuate kisspeptin neurons revealed that the normal episodic activity of these neurons is rapidly suppressed in pregnancy and this was maintained throughout early lactation. Deletion of Prlr from arcuate kisspeptin neurons resulted in early reactivation of episodic activity of kisspeptin neurons prior to a premature return of reproductive cycles in early lactation. These observations show dynamic variation in arcuate kisspeptin neuronal activity associated with the hormonal changes of pregnancy and lactation, and provide direct evidence that prolactin action on arcuate kisspeptin neurons is necessary for suppressing fertility during lactation in mice.