bluuebunny/crossref_metadata_2025 huggingface dataset:
Experience with Contraceptive Dosage Forms and Interest in Novel PrEP Technologies in Women
Authors: Jansen van Vuuren Claudia J. , Lewis Lara , Harkoo Ishana , Dawood Halima , Mansoor Leila E.
Published: May 2023

New pre-exposure prophylaxis (PrEP) strategies tailored to the needs and expectations of individuals at risk of HIV acquisition are needed. In the CAPRISA 082 prospective cohort study in KwaZulu-Natal, South Africa, sexually active women aged 18 to 30 reported, through interviewer-administered questionnaires, on their prior contraceptive experience and interest in both approved and potential future PrEP dosage forms (oral PrEP, long-acting injectable PrEP, and PrEP implants) between March 2016 and February 2018. Univariable and multivariable Poisson regression models with robust standard errors were used to detect associations between women’s prior and current contraceptive use and interest in PrEP options. Of 425 women enrolled, 381 (89.6%) had used at least one modern female contraceptive method previously, with injectable depot medroxyprogesterone acetate (DMPA) being used by 79.8% (n = 339). Women were more likely to show interest in a future PrEP implant if they were currently using (aRR 2.1, CI 1.43–3.07, p = 0.0001) or had ever used (aRR 1.65, CI 1.14–2.40, p = 0.0087) a contraceptive implant, and were more likely to choose an implant as their first choice method than the implant-naïve (current users aRR 3.2, CI 1.79–5.73, p < 0.0001; “ever” users aRR 2.12, CI 1.16–3.86, p = 0.0142). Women were more interested in injectable PrEP if they had used injectable contraceptives (current users aRR 1.24, CI 1.06–1.46, p = 0.0088; “ever” users aRR 1.72, CI 1.20–2.48, p = 0.0033); and were more interested in oral PrEP if they had ever used oral contraceptives (aRR 1.3, CI 1.06–1.59, p = 0.0114). This apparent relationship between women’s contraceptive experience and their interest in novel forms of PrEP in an equivalent dosage form may play a future role in strengthening HIV prevention efforts in women at high risk of HIV acquisition.
American Indian/Alaska Native men are less likely to receive prostate-specific antigen testing and digital rectal exams from primary care providers than White men: a secondary analysis of the National Ambulatory Medical Care Survey from 2012–2018
Authors: Gillette Chris , Locklear Tony , Bell Ronny , Bates Nathan , Ostermann Jan , Reuland Daniel , Foley Kristie , Lashmit Cheyenne , Crandall Sonia
Published: May 2023

Purpose

(1) Identify the proportion of primary care visits in which American Indian/Alaska Native (AI/AN) men receive a prostate-specific antigen test (PSAT)and/or a digital rectal exam (DRE), (2) describe characteristics of primary care visits in which AI/AN receive PSA and/or DRE, and (3) identify whether AI/AN receive PSA and/or DRE less often than non-Hispanic White (nHW) men.

Methods

This was a secondary analysis of the National Ambulatory Medical Care Survey (NAMCS) during 2013–2016 and 2018 and the NAMCS Community Health Center (CHC) datasets from 2012–2015. Weighted bivariate and multivariable tests analyzed the data to account for the complex survey design.

Results

For AI/AN men, 1.67 per 100 visits (95% CI = 0–4.24) included a PSATs (or PSAT) and 0 visits included a DRE between 2013–2016 and 2018. The rate of PSA for non-AI/AN men was 9.35 per 100 visits (95% CI = 7.78–10.91) and 2.52 per 100 visits (95% CI = 1.61–3.42) for DRE. AI/AN men were significantly less likely to receive a PSA than nHW men (aOR = 0.09, 95% CI = 0.01–0.83). In CHCs, AI/AN men experienced 4.26 PSAT per 100 visits (95% CI = 0.96–7.57) compared to 5.00 PSAT per 100 visits (95% CI = 4.40–5.68) for non-AI/AN men. DRE rates for AI/AN men was 0.63 per 100 visits (95% CI = 0–1.61) compared to 1.05 per 100 (95% CI = 0.74–1.37) for non-AI/AN men. There was not a statistically significant disparity in the CHC data regarding PSA (OR = 0.91, 95% CI = 0.42–1.98) or DRE (OR = 0.75, 95% CI = 0.15–3.74), compared to nHW men.

Conclusion

Efforts are needed to better understand why providers may not use PSA and DRE with AI/AN men compared to nHW men.
Impact of land use and land cover change on land degradation in rural semi-arid South Africa: case of the Greater Sekhukhune District Municipality
Authors: Kgaphola M. J. , Ramoelo A. , Odindi J. , Mwenge Kahinda J-M. , Seetal A. R. , Musvoto C.
Published: May 2023

In semi-arid regions, interactions between biophysical and socio-economic variables are complex. Such interactions and their respective variables significantly alter land use and land cover, degrade landscape’s structure, and impede the efficacy of the adopted land management interventions. This scenario is particularly prevalent in communal land tenure system or areas managed by a hybrid of traditional and state led institutions. Hence, this study sought to investigate the impacts of land use and land cover changes (LULCCs) on land degradation (LD) under communal rural districts, and the key drivers of habitat fragmentation in the Greater Sekhukhune District Municipality (GSDM), South Africa. The study used the wet and dry season multi-temporal remotely sensed image data, key-informant interviews, and workshop with tribal council to determine the major drivers of LULCC and LD. Results revealed that mines and quarries, subsistence and commercial cultivation, and thicket/dense bush LULCs declined significantly during the study period. These LULCs mostly declined in wet season, with loss in vegetation cover highly prevalent. Specifically, the highest conversions were from shrub/grassland to bare soil, thicket/dense bush to shrub/grassland, and shrub/grassland to residential, respectively. Generally, LULCC affected vegetation productivity within the study area, with increased negative NDVI values observed during the dry season. The findings from key informants and the tribal council workshop emphasized that soil erosion, abandonment of cropland, and injudicious land use (i.e. overgrazing and consequent bush encroachment) have severely degraded the land. The study also established that the degrading land can be attributed to the weakening local communal land management system, particularly the weakening tribal councils. The study recommends an urgent need for collaborative (i.e. government, tribal authorities, and land users) land management through designing relevant multi-stakeholder LD mitigation measures.
A Registry Study of 240 Patients with X-Linked Agammaglobulinemia Living in the USA
Authors: Hernandez-Trujillo Vivian , Zhou Chuan , Scalchunes Christopher , Ochs Hans D. , Sullivan Kathleen E. , Cunningham-Rundles Charlotte , Fuleihan Ramsay L. , Bonilla Francisco A. , Petrovic Aleksandra , Rawlings David J. , de la Morena M. Teresa
Published: May 2023

Purpose

To understand the natural history and clinical outcomes for patients with X-linked agammaglobulinemia (XLA) in the United States utilizing the United States Immunodeficiency Network (USIDNET) patient registry.

Methods

The USIDNET registry was queried for data from XLA patients collected from 1981 to 2019. Data fields included demographics, clinical features before and after diagnosis of XLA, family history, genetic mutation in Bruton’s tyrosine kinase (BTK), laboratory findings, treatment modalities, and mortality.

Results

Data compiled through the USIDNET registry on 240 patients were analyzed. Patient year of birth ranged from 1945 to 2017. Living status was available for 178 patients; 158/178 (88.8%) were alive. Race was reported for 204 patients as follows: White, 148 (72.5%); Black/African American, 23 (11.2%); Hispanic, 20 (9.8%); Asian or Pacific Islander, 6 (2.9%), and other or more than one race, 7 (3.4%). The median age at last entry, age at disease onset, age at diagnosis, and length of time with XLA diagnosis was 15 [range (r) = 1–52 years], 0.8 [r = birth–22.3 years], 2 [r = birth–29 years], and 10 [r = 1–56 years] years respectively. One hundred and forty-one patients (58.7%) were < 18 years of age. Two hundred and twenty-one (92%) patients were receiving IgG replacement (IgGR), 58 (24%) were on prophylactic antibiotics, and 19 (7.9%) were on immunomodulatory drugs. Eighty-six (35.9%) patients had undergone surgical procedures, two had undergone hematopoietic cell transplantation, and two required liver transplantation. The respiratory tract was the most affected organ system (51.2% of patients) followed by gastrointestinal (40%), neurological (35.4%), and musculoskeletal (28.3%). Infections were common both before and after diagnosis, despite IgGR therapy. Bacteremia/sepsis and meningitis were reported more frequently before XLA diagnosis while encephalitis was more commonly reported after diagnosis. Twenty patients had died (11.2%). The median age of death was 21 years (range = 3–56.7 years). Neurologic condition was the most common underlying co-morbidity for those XLA patients who died.

Conclusions

Current therapies for XLA patients reduce early mortality, but patients continue to experience complications that impact organ function. With improved life expectancy, more efforts will be required to improve post-diagnosis organ dysfunction and quality of life. Neurologic manifestations are an important co-morbidity associated with mortality and not yet clearly fully understood.
Revisiting the Origins of EMDR
Authors: M. Rosen Gerald
Published: May 2023

Francine Shapiro, the founder of Eye Movement Desensitization and Reprocessing (EMDR), reported that the therapeutic use of eye movement patterns was discovered by chance while walking in a park. An alternative accounting for the origins of EMDR comes from research that demonstrates individuals are unable to perceive their own eye movements and from historical sources that document Shapiro’s acceptance of Neuro-Linguistic Programming theory on eye movement patterns and super-achievers. The present paper brings together this diverse set of findings to provide a more accurate context within which Shapiro’s purported discoveries and subsequent claims can best be viewed.
Prenatal Substance Exposure and Neonatal Abstinence Syndrome: State Estimates from the 2016–2020 Transformed Medicaid Statistical Information System
Authors: West Kristina D. , Ali Mir M. , Blanco Martin , Natzke Brenda , Nguyen Linda
Published: May 2023

Introduction

Estimating Neonatal Abstinence Syndrome (NAS) and prenatal substance exposure rates in Medicaid can help target program efforts to improve access to services.

Methods

The data for this study was extracted from the 2016–2020 Transformed Medicaid Statistical Information System (T-MSIS) Analytic Files (TAF) Research Identifiable Files (RIF) and included infants born between January 1, 2016 and December 31, 2020 with a either a NAS diagnosis or prenatal substance exposure.

Results

Between 2016 and 2020, the estimated national rate of NAS experienced a 18% decline, while the estimated national rate of prenatal substance exposure experienced a 3.6% increase. At the state level in 2020, the NAS rate ranged from 3.2 per 1000 births (Hawaii) to 68.0 per 1000 births (West Virginia). Between 2016 and 2020, 28 states experienced a decline in NAS births and 20 states had an increase in NAS rates. In 2020, the lowest prenatal substance exposure rate was observed in New Jersey (9.9 per 1000 births) and the highest in West Virginia (88.1 per 1000 births). Between 2016 and 2020, 38 states experienced an increase in the rate of prenatal substance exposure and 10 states experienced a decline.

Discussion

Estimated rate of NAS has declined nationally, but rate of prenatal substance exposure has increased, with considerable state-level variation. The reported increase in prenatal substance exposure in the majority of US states (38) suggest that substances other than opioids are influencing this trend. Medicaid-led initiatives can be used to identify women with substance use and connect them to services.
Temporally consistent sequence-to-sequence translation of cataract surgeries
Authors: Frisch Yannik , Fuchs Moritz , Mukhopadhyay Anirban
Published: May 2023

Purpose

Image-to-image translation methods can address the lack of diversity in publicly available cataract surgery data. However, applying image-to-image translation to videos—which are frequently used in medical downstream applications—induces artifacts. Additional spatio-temporal constraints are needed to produce realistic translations and improve the temporal consistency of translated image sequences.

Methods

We introduce a motion-translation module that translates optical flows between domains to impose such constraints. We combine it with a shared latent space translation model to improve image quality. Evaluations are conducted regarding translated sequences’ image quality and temporal consistency, where we propose novel quantitative metrics for the latter. Finally, the downstream task of surgical phase classification is evaluated when retraining it with additional synthetic translated data.

Results

Our proposed method produces more consistent translations than state-of-the-art baselines. Moreover, it stays competitive in terms of the per-image translation quality. We further show the benefit of consistently translated cataract surgery sequences for improving the downstream task of surgical phase prediction.

Conclusion

The proposed module increases the temporal consistency of translated sequences. Furthermore, imposed temporal constraints increase the usability of translated data in downstream tasks. This allows overcoming some of the hurdles of surgical data acquisition and annotation and enables improving models’ performance by translating between existing datasets of sequential frames.
Clinical Outcomes for Previously Treated Patients with Advanced Gastric or Gastroesophageal Junction Cancer: A Systematic Literature Review and Meta-Analysis
Authors: Abderhalden Lauren A. , Wu Ping , Amonkar Mayur M. , Lang Brian M. , Shah Sukrut , Jin Fan , Frederickson Andrew M. , Mojebi Ali
Published: May 2023

Purpose

Although second-line treatments improve survival compared to best supportive care in patients with advanced gastric cancer with disease progression on first-line therapy, prognosis remains poor. A systematic review and meta-analysis were conducted to quantify the efficacy of second-or-later line systemic therapies in this target population.

Methods

A systematic literature review (January 1, 2000 to July 6, 2021) of Embase, MEDLINE, and CENTRAL with additional searches of 2019–2021 annual ASCO and ESMO conferences was conducted to identify studies in the target population. A random-effects meta-analysis was performed among studies involving chemotherapies and targeted therapies relevant in treatment guidelines and HTA activities. Outcomes of interest were objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) presented as Kaplan–Meier data. Randomized controlled trials reporting any of the outcomes of interest were included. For OS and PFS, individual patient-level data were reconstructed from published Kaplan–Meier curves.

Results

Forty-four trials were eligible for the analysis. Pooled ORR (42 trials; 77 treatment arms; 7256 participants) was 15.0% (95% confidence interval (CI) 12.7–17.5%). Median OS from the pooled analysis (34 trials; 64 treatment arms; 60,350 person-months) was 7.9 months (95% CI 7.4–8.5). Median PFS from the pooled analysis (32 trials; 61 treatment arms; 28,860 person-months) was 3.5 months (95% CI 3.2–3.7).

Conclusion

Our study confirms poor prognosis among patients with advanced gastric cancer, following disease progression on first-line therapy. Despite the approved, recommended, and experimental systemic treatments available, there is still an unmet need for novel interventions for this indication.
Investigating the influence of agent modality and expression on agent-mediated fairness behaviours
Authors: Yip Hiu Lam , Petrini Karin
Published: May 2023

With technological developments, individuals are increasingly able to delegate tasks to autonomous agents that act on their behalf. This may cause individuals to behave more fairly, as involving an agent representative encourages individuals to strategise ahead and therefore adhere to social norms of fairness. Research suggests that an audio smiling agent may further promote fairness as it provides a signal of honesty and trust. What is still unclear is whether presenting a multimodal smiling agent (by using visual and auditory cues) rather than a unimodal smiling agent as normally available commercially (using only an auditory cue e.g., Siri) could amplify the impact of smiles. In the present study, participants (N = 86) played an ultimatum game either directly with another player (control), through a smiling multimodal and unimodal agent or through a neutral multimodal and unimodal agent. Participants’ task was to offer a number of tickets to the other player from a fixed amount. Results showed that when playing the ultimatum game through a smiling multimodal agent, participants offered more tickets to the other player compared to the control condition and the other agent conditions. Hence, exploiting multisensory perception to enhance an agent’s expression may be key for increasing individuals' pro-social behaviour when interacting through such an agent.
Cardiac Perfusion and Innervation Assessment by CZT-SPECT: Have a Look to Simultaneous Dual-isotope Protocol
Authors: D’Antonio Adriana , Falzarano Maria , Reina Fabrizio , Assante Roberta , Zampella Emilia , Maio Francesca , Buongiorno Pietro , Panico Mariarosaria , Mainolfi Ciro Gabriele , Mannarino Teresa , Cuocolo Alberto , Acampa Wanda
Published: May 2023

Purpose of Review

The purpose of this review is to provide a summary on the status of the art of simultaneous perfusion-innervation imaging by CZT-SPECT and to clarify its potential applications in clinical practice.

Recent Findings

Introduction of CZT cameras represented a critical breakthrough in nuclear cardiology. Although it has been demonstrated that cardiac innervation may be easily assessed by CZT-SPECT, as for now, there are only few studies investigating cardiac perfusion and innervation with simultaneous dual-isotope imaging by CZT cameras.

Perfusion and innervation assessment by CZT camera is a feasible tool, allowing to reduce radiation dose exposure and acquisition time, thanks to CZT better spatial, temporal, and energy resolution, with higher compliance by patients. Moreover, this technique allows to integrate regional evaluation of myocardial perfusion/innervation status, providing more accurate information for risk stratification of different cardiac disease.
Deep face segmentation for improved heart and respiratory rate estimation from videos
Authors: Fiedler Marc-André , Werner Philipp , Rapczyński Michał , Al-Hamadi Ayoub
Published: May 2023

The selection of a suitable region of interest (ROI) is of great importance in camera-based vital signs estimation, as it represents the first step in the processing pipeline. Since all further processing relies on the quality of the signal extracted from the ROI, the tracking of this area is decisive for the performance of the overall algorithm. To overcome the limitations of classical approaches for the ROI, such as partial occlusions or illumination variations, a custom neural network for pixel-precise face segmentation called FaSeNet was developed. It achieves better segmentation results on two datasets compared to state-of-the-art architectures while maintaining high execution efficiency. Furthermore, the Matthews Correlation Coefficient was proposed as a loss function providing a better fitting of the network weights than commonly applied losses in the field of multi-class segmentation. In an extensive evaluation with a variety of algorithms for vital signs estimation, our FaSeNet was able to achieve better results in both heart and respiratory rate estimation. Thus, a ROI for vital signs estimation could be created that is superior to other approaches.
The role of myeloid-derived suppressor cells in liver cancer
Authors: Zhou Shiyue , Zhao Zixuan , Zhong Hao , Ren Zehao , Li Yuye , Wang Hong , Qiu Yuling
Published: May 2023

MDSCs are immature myeloid immune cells, which accumulate in models of liver cancer to reduce effector immune cell activity, contribute to immune escape and treatment resistance. The accumulation of MDSCs suppresses the role of CTL and the killing effects of NK cells, induces the accumulation of Treg cells, and blocks the antigen presentation of DCs, thus promoting the progression of liver cancer. Recently, immunotherapy has emerged a valuable approach following chemoradiotherapy in the therapy of advanced liver cancer. A considerable increasing of researches had proved that targeting MDSCs has become one of the therapeutic targets to enhance tumor immunity. In preclinical study models, targeting MDSCs have shown encouraging results in both alone and in combination administration. In this paper, we elaborated immune microenvironment of the liver, function and regulatory mechanisms of MDSCs, and therapeutic approaches to target MDSCs. We also expect these strategies to supply new views for future immunotherapy for the treatment of liver cancer.
Evolutionary Techniques for the Solution of Bio-Heat Equation Arising in Human Dermal Region Model
Authors: Ahmad Iftikhar , Ilyas Hira , Hussain Syed Ibrar , Raja Muhammad Asif Zahoor
Published: May 2023

The proposed research work analyzes the bio-inspired problem through artificial neural networks with a feed-forward approach utilized to approximate the numerical results for singular nonlinear bio-heat equation (BHE) with boundary conditions based on four different scenarios created on the variation of environmental temperature to illustrate the effects of temperature on the human dermal region. The log-sigmoid function is used to construct the fitness function, while the optimization solvers: pattern search and genetic algorithm, are then hybridized with the active set technique, interior point technique, sequential quadratic programming for accurate and reliable results of the proposed BHE with various scenarios where the convergence of the numerical results is also analyzed. Moreover, a comparison of the proposed technique is expressed through residual error that reveals the nature of the numerical results and their efficiency. Additionally, a comprehensive statistical analysis is presented for the designed technique to better illustrate the accuracy, reliability, and efficiency of the obtained results.
Immune-Ageing Evaluation of Peripheral T and NK Lymphocyte Subsets in Chinese Healthy Adults
Authors: Jia Zhenghu , Ren Zhiyao , Ye Dongmei , Li Jiawei , Xu Yan , Liu Hui , Meng Ziyu , Yang Chengmao , Chen Xiaqi , Mao Xinru , Luo Xueli , Yang Zhe , Ma Lina , Deng Anyi , Li Yafang , Han Bingyu , Wei Junping , Huang Chongcheng , Xiang Zheng , Chen Guobing , Li Peiling , Ouyang Juan , Chen Peisong , Luo Oscar Junhong , Gao Yifang , Yin Zhinan
Published: May 2023

Ageing is often accompanied with a decline in immune system function, resulting in immune ageing. Numerous studies have focussed on the changes in different lymphocyte subsets in diseases and immunosenescence. The change in immune phenotype is a key indication of the diseased or healthy status. However, the changes in lymphocyte number and phenotype brought about by ageing have not been comprehensively analysed. Here, we analysed T and natural killer (NK) cell subsets, the phenotype and cell differentiation states in 43,096 healthy individuals, aged 20–88 years, without known diseases. Thirty-six immune parameters were analysed and the reference ranges of these subsets were established in different age groups divided into 5-year intervals. The data were subjected to random forest machine learning for immune-ageing modelling and confirmed using the neural network analysis. Our initial analysis and machine modelling prediction showed that naïve T cells decreased with ageing, whereas central memory T cells (Tcm) and effector memory T cells (Tem) increased cluster of differentiation (CD) 28-associated T cells. This is the largest study to investigate the correlation between age and immune cell function in a Chinese population, and provides insightful differences, suggesting that healthy adults might be considerably influenced by age and sex. The age of a person's immune system might be different from their chronological age. Our immune-ageing modelling study is one of the largest studies to provide insights into ‘immune-age’ rather than ‘biological-age’. Through machine learning, we identified immune factors influencing the most through ageing and built a model for immune-ageing prediction. Our research not only reveals the impact of age on immune parameter differences within the Chinese population, but also provides new insights for monitoring and preventing some diseases in clinical practice.
Forensic Linguistics in Australia
Authors: Eades Diana , Fraser Helen , Heydon Georgina
Published: May 2023

This Element presents an account of forensic linguistics in Australia since the first expert linguistic evidence in 1959, through early work in the 1970s-1980s, the defining of the discipline in the 1990s, and into the current era. It starts with a consideration of some widespread misconceptions about language that affect the field and some problematic ideologies in the law, which underly much of the discussion throughout the Element. The authors' report of forensic linguists' work is structured in terms of the linguistic, interactional and sociocultural contexts of the language data being analysed, whether in expert evidence, in research, or in practical applications of linguistics in a range of legal settings. The Element concludes by highlighting mutual engagement between forensic linguistic practitioners and both the judiciary and legal scholars, and outlines some of the key factors which support a critical forensic linguistics approach in much of the work in the authors' country.
Naked men on the run, regression to childhood: cultural figures of the trauma during the First World War
Authors: Fiorino Vinzia
Published: May 2023

Although there is a wide-ranging historiography dealing with psychoneurosis, various manifestations of psychic suffering widespread among traumatised soldiers during the Great War have received less attention. This essay, based on an analysis of soldiers' clinical files in Italian psychiatric hospitals, draws out these phenomena. The main forms assumed by this kind of trauma are three: soldiers who strip off their uniform and wander around naked; a sort of regression to childhood; and a particular type of hysteria. The essay stresses how existingstereotypes about women were adapted to form a new way of describing masculinity in crisis, and the new political subject: the masses. Too many emotions, too many nerves, define the affected men: they are subjects deprived of personality, and their predicament highlights the transition from soldier-hero to mass-soldier.
Racial Integration, Cost-Benefit Analysis, and Philosophical Humility
Authors: Stanley Sharon
Published: May 2023

D. C. Matthew offers an original and important critique of racial integration. His claim that integration will aggravate phenotypic devaluation of blackness, threatening black self-worth, is persuasive. However, his stronger normative argument that blacks should reject integration as a consequence because the potential harms to black self-worth outweigh its purported benefits is less convincing, as it rests on a dubious cost-benefit analysis. Ultimately, I argue that we should resist the impulse to offer a definitive cost-benefit analysis of racial integration in any case, given the uncertainty of such a complex process unfolding in a speculative future.
Integration and Reaction
Authors: Sundstrom Ronald R.
Published: May 2023

D. C. Matthew argues that although integration offers blacks social and economic benefits, it also creates the conditions for phenotypic devaluation that leads to harm against black self-worth and servile behaviour. Therefore, he advises against integration because the resulting self-worth harms outweigh the benefits of integration. I argue that Matthew's cost-benefit calculation against integration lacks the requisite evidence, and amounts to a luxury belief that will result in more harm. Moreover, his interpretation of behaviour — which he construes as being indicative of a lack of self-worth — is unfounded. Further, his cost-benefit calculation results in socially reactionary sexual policing and ideological purity tests.
L'argument de Quine contre les logiques déviantes
Authors: Wagner Henri
Published: May 2023

L'ambition de cet article est de restituer la radicalité de l'argument central contre les logiques déviantes que W.V.O. Quine déploie dans Philosophy of Logic. Cet argument a pour objet de mettre au jour l'inanité du concept de logique déviante, c'est-à-dire son caractère dénué de sens. En rendre compte requiert alors de prendre la mesure de sa dimension anti-psychologiste. Nous tâchons ainsi de montrer que le défi le plus radical de Quine ne consiste pas à opposer au logicien déviant que changer de lois logiques, c'est changer la signification des termes de constantes logiques.
Investigating the shared genetic architecture of post-traumatic stress disorder and gastrointestinal tract disorders: a genome-wide cross-trait analysis
Authors: Zhou Siquan , Luo Hang , Tian Ye , Li Haoqi , Zeng Yaxian , Wang Xiaoyu , Shan Shufang , Xiong Jingyuan , Cheng Guo
Published: May 2023

Background

Observational studies suggest a correlation between post-traumatic stress disorder (PTSD) and gastrointestinal tract (GIT) disorders. However, the genetic overlap, causal relationships, and underlining mechanisms between PTSD and GIT disorders were absent.

Methods

We obtained genome-wide association study statistics for PTSD (23 212 cases, 151 447 controls), peptic ulcer disease (PUD; 16 666 cases, 439 661 controls), gastroesophageal reflux disease (GORD; 54 854 cases, 401 473 controls), PUD and/or GORD and/or medications (PGM; 90 175 cases, 366 152 controls), irritable bowel syndrome (IBS; 28 518 cases, 426 803 controls), and inflammatory bowel disease (IBD; 7045 cases, 449 282 controls). We quantified genetic correlations, identified pleiotropic loci, and performed multi-marker analysis of genomic annotation, fast gene-based association analysis, transcriptome-wide association study analysis, and bidirectional Mendelian randomization analysis.

Results

PTSD globally correlates with PUD (rg = 0.526, p = 9.355 × 10−7), GORD (rg = 0.398, p = 5.223 × 10−9), PGM (rg = 0.524, p = 1.251 × 10−15), and IBS (rg = 0.419, p = 8.825 × 10−6). Cross-trait meta-analyses identify seven genome-wide significant loci between PTSD and PGM (rs13107325, rs1632855, rs1800628, rs2188100, rs3129953, rs6973700, and rs73154693); three between PTSD and GORD (rs13107325, rs1632855, and rs3132450); one between PTSD and IBS/IBD (rs4937872 and rs114969413, respectively). Proximal pleiotropic genes are mainly enriched in immune response regulatory pathways, and in brain, digestive, and immune systems. Gene-level analyses identify five candidates: ABT1, BTN3A2, HIST1H3J, ZKSCAN4, and ZKSCAN8. We found significant causal effects of GORD, PGM, IBS, and IBD on PTSD. We observed no reverse causality of PTSD with GIT disorders, except for GORD.

Conclusions

PTSD and GIT disorders share common genetic architectures. Our work offers insights into the biological mechanisms, and provides genetic basis for translational research studies.
A domain-theoretic framework for robustness analysis of neural networks
Authors: Zhou Can , Shaikh Razin A. , Li Yiran , Farjudian Amin
Published: May 2023

A domain-theoretic framework is presented for validated robustness analysis of neural networks. First, global robustness of a general class of networks is analyzed. Then, using the fact that Edalat’s domain-theoreticL-derivative coincides with Clarke’s generalized gradient, the framework is extended for attack-agnostic local robustness analysis. The proposed framework is ideal for designing algorithms which are correct by construction. This claim is exemplified by developing a validated algorithm for estimation of Lipschitz constant of feedforward regressors. The completeness of the algorithm is proved over differentiable networks and also over general position${\mathrm{ReLU}}$networks. Computability results are obtained within the framework of effectively given domains. Using the proposed domain model, differentiable and non-differentiable networks can be analyzed uniformly. The validated algorithm is implemented using arbitrary-precision interval arithmetic, and the results of some experiments are presented. The software implementation is truly validated, as it handles floating-point errors as well.
Soil Moisture Variations From Boreal Forests to the Tundra
Authors: Kemppinen J. , Niittynen P. , Rissanen T. , Tyystjärvi V. , Aalto J. , Luoto M.
Published: May 2023

Soil moisture has a profound influence on life on Earth, and this vital water resource varies across space and time. Here, we explored soil moisture variations in boreal forest and tundra environments, where comprehensive soil moisture datasets are scarce. We installed soil moisture sensors up to 14 cm depth at 503 measurement sites within seven study areas across northern Europe. We recorded 6,138,528 measurements to capture soil moisture variations of the snowless season from April to September 2020. We described the spatio‐temporal patterns of soil moisture, and test how these patterns are linked to topography and how these links vary in space and time. We found large spatial variation and often less pronounced temporal variation in soil moisture across the measurement sites within all study areas. We found that throughout the measurement periods both univariate and multivariate models with topographic predictors showed great temporal variation in their performance and in the relative influence of the predictors within and across the areas. We found that the soil moisture‐topography relationships are site‐specific, as the topography‐based models often performed poorly when transferred from one area to another. There was no general solution that would work well in all the study areas when modeling soil moisture variation with topography. This should be carefully considered before applying topographic proxies for soil moisture. Overall, these data and results highlight the strong spatio‐temporal heterogeneity of soil moisture conditions in boreal forest and tundra environments.
Pangenomics of the death cap mushroom Amanita phalloides, and of Agaricales, reveals dynamic evolution of toxin genes in an invasive range
Authors: Drott Milton T , Park Sung Chul , Wang Yen-wen , Harrow Lynn , Keller Nancy P , Pringle Anne
Published: May 2023

The poisonous European mushroom Amanita phalloides (the “death cap”) is invading California. Whether the death caps’ toxic secondary metabolites are evolving as it invades is unknown. We developed a bioinformatic pipeline to identify the MSDIN genes underpinning toxicity and probed 88 death cap genomes from an invasive Californian population and from the European range, discovering a previously unsuspected diversity of MSDINs made up of both core and accessory elements. Each death cap individual possesses a unique suite of MSDINs, and toxin genes are significantly differentiated between Californian and European samples. MSDIN genes are maintained by strong natural selection, and chemical profiling confirms MSDIN genes are expressed and result in distinct phenotypes; our chemical profiling also identified a new MSDIN peptide. Toxin genes are physically clustered within genomes. We contextualize our discoveries by probing for MSDINs in genomes from across the order Agaricales, revealing MSDIN diversity originated in independent gene family expansions among genera. We also report the discovery of an MSDIN in an Amanita outside the “lethal Amanitas” clade. Finally, the identification of an MSDIN gene and its associated processing gene (POPB) in Clavaria fumosa suggest the origin of MSDINs is older than previously suspected. The dynamic evolution of MSDINs underscores their potential to mediate ecological interactions, implicating MSDINs in the ongoing invasion. Our data change the understanding of the evolutionary history of poisonous mushrooms, emphasizing striking parallels to convergently evolved animal toxins. Our pipeline provides a roadmap for exploring secondary metabolites in other basidiomycetes and will enable drug prospecting.
Whey-based diet containing medium chain triglycerides modulates the gut microbiota and protects the intestinal mucosa from chemotherapy while maintaining therapy efficacy
Authors: Wardill Hannah R. , Da Silva Ferreira Ana Rita , Kumar Himanshu , Bateman Emma H. , Cross Courtney B. , Bowen Joanne M. , Havinga Rick , Harmsen Hermie J. M. , Knol Jan , Dorresteijn Bram , van Dijk Miriam , van Bergenhenegouwen Jeroen , Tissing Wim J. E.
Published: May 2023

Cytotoxicity (i.e. cell death) is the core mechanism by which chemotherapy induces its anti-cancer effects. Unfortunately, this same mechanism underpins the collateral damage it causes to healthy tissues. The gastrointestinal tract is highly susceptible to chemotherapy’s cytotoxicity, resulting in ulcerative lesions (termed gastrointestinal mucositis, GI-M) that impair the functional capacity of the gut leading to diarrhea, anorexia, malnutrition and weight loss, which negatively impact physical/psychological wellbeing and treatment adherence. Preventing these side effects has proven challenging given the overlapping mechanisms that dictate chemotherapy efficacy and toxicity. Here, we report on a novel dietary intervention that, due to its localized gastrointestinal effects, is able to protect the intestinal mucosal from unwanted toxicity without impairing the anti-tumor effects of chemotherapy. The test diet (containing extensively hydrolyzed whey protein and medium chain triglycerides (MCTs)), was investigated in both tumor-naïve and tumor-bearing models to evaluate its effect on GI-M and chemo-efficacy, respectively. In both models, methotrexate was used as the representative chemotherapeutic agent and the diet was provided ad libitum for 14 days prior to treatment. GI-M was measured using the validated biomarker plasma citrulline, and chemo-efficacy defined by tumor burden (cm3/g body weight). The test diet significantly attenuated GI-M (P = 0.03), with associated reductions in diarrhea (P < 0.0001), weight loss (P < 0.05), daily activity (P < 0.02) and maintenance of body composition (P < 0.02). Moreover, the test diet showed significant impact on gut microbiota by increasing diversity and resilience, whilst also altering microbial composition and function (indicated by cecal short and brained chain fatty acids). The test diet did not impair the efficacy of methotrexate against mammary adenocarcinoma (tumor) cells. In line with the first model, the test diet minimized intestinal injury (P = 0.001) and diarrhea (P < 0.0001). These data support translational initiatives to determine the clinical feasibility, utility and efficacy of this diet to improve chemotherapy treatment outcomes.
Intricacies of TGF-β signaling in Treg and Th17 cell biology
Authors: Wang Junying , Zhao Xingqi , Wan Yisong Y.
Published: May 2023

Balanced immunity is pivotal for health and homeostasis. CD4+ helper T (Th) cells are central to the balance between immune tolerance and immune rejection. Th cells adopt distinct functions to maintain tolerance and clear pathogens. Dysregulation of Th cell function often leads to maladies, including autoimmunity, inflammatory disease, cancer, and infection. Regulatory T (Treg) and Th17 cells are critical Th cell types involved in immune tolerance, homeostasis, pathogenicity, and pathogen clearance. It is therefore critical to understand how Treg and Th17 cells are regulated in health and disease. Cytokines are instrumental in directing Treg and Th17 cell function. The evolutionarily conserved TGF-β (transforming growth factor-β) cytokine superfamily is of particular interest because it is central to the biology of both Treg cells that are predominantly immunosuppressive and Th17 cells that can be proinflammatory, pathogenic, and immune regulatory. How TGF-β superfamily members and their intricate signaling pathways regulate Treg and Th17 cell function is a question that has been intensely investigated for two decades. Here, we introduce the fundamental biology of TGF-β superfamily signaling, Treg cells, and Th17 cells and discuss in detail how the TGF-β superfamily contributes to Treg and Th17 cell biology through complex yet ordered and cooperative signaling networks.
Early events in amyloid-β self-assembly probed by time-resolved solid state NMR and light scattering
Authors: Jeon Jaekyun , Yau Wai-Ming , Tycko Robert
Published: May 2023

Self-assembly of amyloid-β peptides leads to oligomers, protofibrils, and fibrils that are likely instigators of neurodegeneration in Alzheimer’s disease. We report results of time-resolved solid state nuclear magnetic resonance (ssNMR) and light scattering experiments on 40-residue amyloid-β (Aβ40) that provide structural information for oligomers that form on time scales from 0.7 ms to 1.0 h after initiation of self-assembly by a rapid pH drop. Low-temperature ssNMR spectra of freeze-trapped intermediates indicate that β-strand conformations within and contacts between the two main hydrophobic segments of Aβ40 develop within 1 ms, while light scattering data imply a primarily monomeric state up to 5 ms. Intermolecular contacts involving residues 18 and 33 develop within 0.5 s, at which time Aβ40 is approximately octameric. These contacts argue against β-sheet organizations resembling those found previously in protofibrils and fibrils. Only minor changes in the Aβ40 conformational distribution are detected as larger assemblies develop.
Comparative mRNA booster effectiveness against death or hospitalization with COVID-19 pneumonia across at-risk US Veteran populations
Authors: Kelly J. Daniel , Leonard Samuel , Boscardin W. John , Hoggatt Katherine J. , Lum Emily N. , Austin Charles C. , Byers Amy , Tien Phyllis C. , Austin Peter C. , Bravata Dawn M. , Keyhani Salomeh
Published: May 2023

Studies of comparative mRNA booster effectiveness among high-risk populations can inform mRNA booster-specific guidelines. The study emulated a target trial of COVID-19 vaccinated U.S. Veterans who received three doses of either mRNA-1273 or BNT162b2 vaccines. Participants were followed for up to 32 weeks between July 1, 2021 to May 30, 2022. Non-overlapping populations were average and high risk; high-risk sub-groups were age ≥65 years, high-risk co-morbid conditions, and immunocompromising conditions. Of 1,703,189 participants, 10.9 per 10,000 persons died or were hospitalized with COVID-19 pneumonia over 32 weeks (95% CI: 10.2, 11.8). Although relative risks of death or hospitalization with COVID-19 pneumonia were similar across at-risk groups, absolute risk varied when comparing three doses of BNT162b2 with mRNA-1273 (BNT162b2 minus mRNA-1273) between average-risk and high-risk populations, confirmed by the presence of additive interaction. The risk difference of death or hospitalization with COVID-19 pneumonia for high-risk populations was 2.2 (0.9, 3.6). Effects were not modified by predominant viral variant. In this work, the risk of death or hospitalization with COVID-19 pneumonia over 32 weeks was lower among high-risk populations who received three doses of mRNA-1273 vaccine instead of BNT162b2 vaccine; no difference was found among the average-risk population and age >65 sub-group.
Cultured meat platform developed through the structuring of edible microcarrier-derived microtissues with oleogel-based fat substitute
Authors: Yen Feng-Chun , Glusac Jovana , Levi Shira , Zernov Anton , Baruch Limor , Davidovich-Pinhas Maya , Fishman Ayelet , Machluf Marcelle
Published: May 2023

With the increasing global demand for meat, cultured meat technologies are emerging, offering more sustainable solutions that aim to evade a future shortage of meat. Here, we demonstrate a cultured meat platform composed of edible microcarriers and an oleogel-based fat substitute. Scalable expansion of bovine mesenchymal stem cells on edible chitosan-collagen microcarriers is optimized to generate cellularized microtissues. In parallel, an oleogel system incorporated with plant protein is developed as a fat substitute, which is comparable to beef fat in appearance and texture. Combining the cellularized microtissues with the developed fat substitute, two types of cultured meat prototypes are introduced: layered cultured meat and burger-like cultured meat. While the layered prototype benefits enhanced stiffness, the burger-like prototype has a marbling meat-like appearance and a softer texture. Overall, this platform and the established technological basis may contribute to the development of different cultured meat products and promote their commercial production.
Plasmodium sporozoite search strategy to locate hotspots of blood vessel invasion
Authors: Formaglio Pauline , Wosniack Marina E. , Tromer Raphael M. , Polli Jaderson G. , Matos Yuri B. , Zhong Hang , Raposo Ernesto P. , da Luz Marcos G. E. , Amino Rogerio
Published: May 2023

Plasmodiumsporozoites actively migrate in the dermis and enter blood vessels to infect the liver. Despite their importance for malaria infection, little is known about these cutaneous processes. We combine intravital imaging in a rodent malaria model and statistical methods to unveil the parasite strategy to reach the bloodstream. We determine that sporozoites display a high-motility mode with a superdiffusive Lévy-like pattern known to optimize the location of scarce targets. When encountering blood vessels, sporozoites frequently switch to a subdiffusive low-motility behavior associated with probing for intravasation hotspots, marked by the presence of pericytes. Hence, sporozoites present anomalous diffusive motility, alternating between superdiffusive tissue exploration and subdiffusive local vessel exploitation, thus optimizing the sequential tasks of seeking blood vessels and pericyte-associated sites of privileged intravasation.
In situ observation of crystal rotation in Ni-based superalloy during additive manufacturing process
Authors: Zhang Dongsheng , Liu Wei , Li Yuxiao , Sun Darui , Wu Yu , Luo Shengnian , Chen Sen , Tao Ye , Zhang Bingbing
Published: May 2023

Understanding the dynamic process of epitaxial microstructure forming in laser additive manufacturing is very important for achieving products with a single crystalline texture. Here, we perform in situ, real-time synchrotron Laue diffraction experiments to capture the microstructural evolution of nickel-based single-crystal superalloys during the rapid laser remelting process. In situ synchrotron radiation Laue diffraction characterises the crystal rotation behaviour and stray grain formation process. With a complementary thermomechanical coupled finite element simulation and molecular dynamics simulation, we identify that the crystal rotation is governed by the localised heating/cooling heterogeneity-induced deformation gradient and recognise that the sub-grain rotation caused by rapid dislocation movement could be the origin of granular stray grains at the bottom of the melt pool.