bluuebunny/crossref_metadata_2025 huggingface dataset:
Fire-modulated fluctuations in nutrient availability stimulate biome-scale floristic turnover in time, and elevated species richness, in low-nutrient fynbos heathland
Authors: Verboom G Anthony , Slingsby Jasper A , Cramer Michael D
Published: December 2023

Background and Aims

In many systems, postfire vegetation recovery is characterized by temporal changes in plant species composition and richness. We attribute this to changes in resource availability with time since fire, with the magnitude of species turnover determined by the degree of resource limitation. Here, we test the hypothesis that postfire species turnover in South African fynbos heathland is powered by fire-modulated changes in nutrient availability, with the magnitude of turnover in nutrient-constrained fynbos being greater than in fertile renosterveld shrubland. We also test the hypothesis that floristic overlaps between fynbos and renosterveld are attributable to nutritional augmentation of fynbos soils immediately after fire.

Methods

We use vegetation survey data from two sites on the Cape Peninsula to compare changes in species richness and composition with time since fire.

Key Results

Fynbos communities display a clear decline in species richness with time since fire, whereas no such decline is apparent in renosterveld. In fynbos, declining species richness is associated with declines in the richness of plant families having high foliar concentrations of nitrogen, phosphorus and potassium and possessing attributes that are nutritionally costly. In contrast, families that dominate late-succession fynbos possess adaptations for the acquisition and retention of sparse nutrients. At the family level, recently burnt fynbos is compositionally more similar to renosterveld than is mature fynbos.

Conclusions

Our data suggest that nutritionally driven species turnover contributes significantly to fynbos community richness. We propose that the extremely low baseline fertility of fynbos soils serves to lengthen the nutritional resource axis along which species can differentiate and coexist, thereby providing the opportunity for low-nutrient extremophiles to coexist spatially with species adapted to more fertile soil. This mechanism has the potential to operate in any resource-constrained system in which episodic disturbance affects resource availability.
Associations Between Generativity and Social Asymmetry Among Older Adults in Japan
Authors: Ong Anthony D , Graham Eileen K , Jackson Kathryn , Atherton Olivia E , Luo Jing , Willroth Emily C , Beck Emorie D , Yoneda Tomiko , Cintron Dakota W , Mroczek Daniel K , Steptoe Andrew
Published: December 2023

Objectives

Loneliness and social isolation are major public health concerns among older adults in Japan. Generativity, the concern for and commitment to future generations, may buffer older adults from loneliness. This study examined the cross-sectional and longitudinal associations between generativity and social asymmetry (the discrepancy between social isolation and loneliness) among older adults in Japan.

Methods

Data were from 2 waves (2008 and 2012) of the Midlife in Japan survey, a nationally representative longitudinal study of 645 adults aged 30–79 residing in the Tokyo metropolitan area. Generativity was measured using the 6-item Loyola Generativity Scale. Social asymmetry was computed as the residual score from regressing loneliness onto social isolation.

Results

Higher generativity levels were associated with lower social asymmetry scores (B=−0.21, SE=0.04), but generativity change across waves did not predict social asymmetry 4 years later (B=−0.04, SE=0.06).

Discussion

Generativity may play a protective role in buffering older adults from the adverse effects of social isolation on loneliness. Promoting generativity among older adults may be a potential intervention strategy to reduce loneliness and improve well-being in aging populations in Japan.
In Darkness We Meet: Annie Ernaux’s Account of Care and Dementia
Authors: Stončikaitė Ieva , Ortega Montero Óscar
Published: December 2023

Background and Objectives

The complexities surrounding aging, dementia, and care are timely issues that transcend beyond institutional boundaries, evincing a critical debate on later life across disciplines. The aim of this study is to offer fresh insights into the intricate paradigms of living and growing older with dementia. The study focuses on the Nobel Prize-winning author Annie Ernaux’s memoir I Remain in Darkness (1999), which provides a candid account of her mother’s journey through dementia from its onset to the gradual decline. 

Research Design and Methods

This article employs the theoretical frameworks of literary gerontology, illness narratives and life writing to address the challenges of aging, dementia and care that are represented in Ernaux’s memoir. It also addresses societal attitudes and stigma associated with aging and dementia by exploring the embarrassment that individuals and families experience when confronted with the deteriorating mental health of their loved ones. 

Results

Ernaux’s memoir explores the nuances of dementia and caregiving within both the familial and institutional context, and sheds light on the complex relationship between a mother and a daughter. Through the act of witnessing, Ernaux embarks on a path of healing, which allows her to confront her past wounds and better navigate the challenges that lie ahead. However, Ernaux’s confessional memoir also troubles the ethics of life writing and identity issues, and seems to perpetuate the pathologizing medical gaze through the exposure of her mother’s vulnerability and intimacy in the face of dementia and care.

Discussion and Implications

Ernaux’s account of her mother’s dementia and aging is both a confessional piece of writing and a narrative therapy, which reveals the challenges of aging, illness, and unresolved family tensions. Her work illuminates the interconnectedness between the past, present, and future, and shows that illness narratives can act as a catalyst for transformative change, identity formation, and self-reflection. The article addresses the intricacies of old age, showcasing how life writing and humanities-based inquiry can bring to the fore key aspects of the latest stages in life, which are often unvoiced because they represent the most unpleasant and feared aspects of aging in contemporary society.
PIECES of My RELATIONSHIPS: The Cultural Adaptation of a Biographical Assessment Tool for Indigenous Older Adults in Canada
Authors: Jacklin Kristen , Pitawanakwat Karen , Blind Melissa , Ketcher Dana , Jones Louise , Piraino Emily , Bretzlaff Monica
Published: December 2023

Background and Objectives

Healthcare services are rarely designed to meet the needs of Indigenous people, resulting in culturally unsafe care and assessment tools. This paper describes a collaboration between North East Behavioural Supports Ontario (NEBSO), university researchers, and Indigenous communities to adapt a biographical assessment tool used by NEBSO to be culturally appropriate and safe for Indigenous older adults (55+) in long-term care facilities in Ontario, Canada.

Research Design and Methods

Over 36 months, this project applied an Indigenized, community-based participatory research (CBPR) and cultural safety framework to the adaptation process. Qualitative data sources include the guidance of an Indigenous Elder, an Anishinaabe Language Expert Group, and focus groups conducted along the North Shore of Lake Huron, Sudbury, and Cochrane, Ontario.

Results

The adapted tool shifts the focus from personhood to relationships, includes culturally relevant domains, and supports trauma-informed approaches. Five themes were identified during the adaptation process: (1) practicing a relational approach to care, (2) valuing Indigenous language, (3) understanding Indigenous trauma, (4) respecting cultural values and understandings, and (5) addressing systemic barriers to culturally safe care.

Discussion and Implications

Themes elucidated from this research process can inform future studies adapting mainstream practice tools and developing new tools for Indigenous populations. The collaboration and approach to this adaptation process demonstrated how cultural safety at systemic and practice levels can be addressed through CPBR partnerships between universities, organizations, and Indigenous communities. Findings support the need to evaluate the cultural safety of other assessments for older Indigenous adults in health care settings.
Protests, long-term preferences, and populism: Evidence from 1968 in Europe
Authors: Fazio Andrea
Published: December 2023

In 1968, young people grew up in an atmosphere of strong dissatisfaction and distrust against the status quo. We show that higher exposure to protests in 1968 leads to higher dissatisfaction toward national governments and raises the probability of voting for populist parties. Consistently with the impressionable years hypothesis, we find these effects valid only for those aged between 18 and 25 years during 1968. Our results are robust to a series of placebo tests and to alternative definitions of our treatment and control groups. We find that our results are driven by individuals with a middle or low level of education. We also find suggestive evidence that the mechanisms driving our results can depend on individuals’ level of education.
Who Should Scale Back? Experimental Evidence on Employer Support for Part-Time Employment and Working Hours Norms for Couples with Young Children
Authors: Philipp Marie-Fleur , Büchau Silke , Schober Pia S
Published: December 2023

This experimental study investigates how hypothetical employer support for part-time work shapes working hours norms for mothers and fathers with young children in Germany. It extends previous studies by focusing on the couple context, for instance by exploring interdependencies with each partner’s earnings potential. The analysis is framed using capability-based explanations combined with a perspective of gender as a social structure. A factorial survey experiment was implemented within the German pairfam panel. Linear and multinomial logistic multilevel regressions were conducted with 5,856 respondents. Hypothetical employer support similarly increases respondents’ recommendations to reduce working hours for mothers and fathers and supports dual part-time arrangements. In couples who face opposing incentives in terms of relative earnings or promotion prospects and employer support for part-time work, prevailing gender norms seem to reinforce the traditionalizing constraints and attenuate the de-traditionalizing influence. Respondents with more egalitarian gender beliefs respond more strongly to paternal employer support.
Host-Specific and Homologous Pairs of Melampsora larici-populina Effectors Unveil Novel Nicotiana benthamiana Stromule Induction Factors
Authors: Letanneur Claire , Brisson Alexandre , Bisaillon Mathias , Devèze Théo , Plourde Mélodie B. , Schattat Martin , Duplessis Sébastien , Germain Hugo
Published: December 2023

The poplar rust fungus Melampsora larici-populina is part of one of the most devastating group of fungi (Pucciniales) and causes important economic losses to the poplar industry. Because M. larici-populina is a heteroecious obligate biotroph, its spread depends on its ability to carry out its reproductive cycle through larch and then poplar parasitism. Genomic approaches have identified more than 1,000 candidate secreted effector proteins (CSEPs) from the predicted secretome of M. larici-populina that are potentially implicated in the infection process. In this study, we selected CSEP pairs (and one triplet) among CSEP gene families that share high sequence homology but display specific gene expression profiles among the two distinct hosts. We determined their subcellular localization by confocal microscopy through expression in the heterologous plant system Nicotiana benthamiana. Five out of nine showed partial or complete chloroplastic localization. We also screened for potential protein interactors from larch and poplar by yeast two-hybrid assays. One pair of CSEPs and the triplet shared common interactors, whereas the members of the two other pairs did not have common targets from either host. Finally, stromule induction quantification revealed that two pairs and the triplet of CSEPs induced stromules when transiently expressed in N. benthamiana. The use of N. benthamiana eds1 and nrg1 knockout lines showed that CSEPs can induce stromules through an eds1-independent mechanism. However, CSEP homologs shared the same impact on stromule induction and contributed to discovering a new stromule induction cascade that can be partially and/or fully independent of eds1.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Career Reflections: Delivering Excellence by Building Great Teams
Authors: Lockwood Charles J.
Published: December 2023

Building great teams who can act rapidly and training energetic leaders who are empowered to innovate have been central themes in my leadership journey: Career reflections of Charles J. Lockwood, MD, MHCM, dean of the USF Health Morsani College of Medicine and executive vice president of USF Health at the University of South Florida (USF).
Real-Life Patient Educational Recording Before Esophageal Manometry
Authors: Yip Coka K. , Kim Linda Y. , Rezaie Ali , Sotelo Cinthya V. , Xu Wenrui , Chang Bianca W. , Winokur Elizabeth J.
Published: December 2023

High-resolution esophageal manometry (HREM) is a fundamental diagnostic tool in esophagology. Educational tools for this procedure have remained scarce. This quality improvement project aimed to develop an enhanced digital recording about HREM and assess the effect on patient knowledge, anxiety, satisfaction, and procedure abortion rates. The Institute for Healthcare Improvement Model for Improvement and the self-regulation theory guided this project. An interprofessional team was formed. A video recording of the pre-, peri-, and post-HREM care was created. Participants were recruited in the following four cycles: Baseline, Workstation, Manometry, and Home. Questionnaires were collected pre- and postvideo education. The results demonstrated a significant increase in knowledge from 60% to 96% (p < .001), 58% to 96% (p < .001), 79% to 96% (p < .001), and 92% to 97% (p = .02) and reductions in anxiety from 7.1 to 5.5 (p = .003), 7.6 to 6.1 (p = .003), 7.1 to 6.5 (p < .001), and 6.4 to 6.1 (p = .03) in all four groups. Almost all (99.5%) participants liked the recorded education and only 2.6% of cases were aborted during the 1-year project implementation period from June 2020 to May 2021. Findings from this project support the positive impact of recorded patient education. An educational recording is standardized and has the potential to be implemented in variable settings.
STELLATE GANGLION BLOCK REVERSES PHSML-INDUCED VASCULAR HYPOREACTIVITY THROUGH INHIBITING AUTOPHAGY-MEDIATED PHENOTYPIC TRANSFORMATION OF VSMCs
Authors: Li Cai-Juan , Du Hui-Bo , Zhao Zhen-Ao , Sun Qi , Li Yi-Ming , Chen Si-Jie , Zhang Hong , Zhang Nan , Niu Chun-Yu , Zhao Zi-Gang
Published: December 2023

Posthemorrhagic shock mesenteric lymph (PHSML) return–contributed excessive autophagy of vascular smooth muscle cells (VSMCs) is involved in vascular hyporeactivity, which is inhibited by stellate ganglion block (SGB) treatment. The contractile phenotype of VSMCs transforms into a synthetic phenotype after stimulation with excessive autophagy. Therefore, we hypothesized that SGB ameliorates PHSML-induced vascular hyporeactivity by inhibiting autophagy-mediated phenotypic transformation of VSMCs. To substantiate this hypothesis, a hemorrhagic shock model in conscious rats was used to observe the effects of SGB intervention or intravenous infusion of the autophagy inhibitor 3-methyladenine (3-MA) on intestinal blood flow and the expression of autophagy- and phenotype-defining proteins in mesenteric secondary artery tissues. We also investigated the effects of intraperitoneal administration of PHSML intravenous infusion and the autophagy agonist rapamycin (RAPA) on the beneficial effect of SGB. The results showed that hemorrhagic shock decreased intestinal blood flow and enhanced the expression of LC3 II/I, Beclin 1, and matrix metalloproteinase 2, which were reversed by SGB or 3-MA treatment. In contrast, RAPA and PHSML administration abolished the beneficial effects of SGB. Furthermore, the effects of PHSML or PHSML obtained from rats treated with SGB (PHSML-SGB) on cellular contractility, autophagy, and VSMC phenotype were explored. Meanwhile, the effects of 3-MA on PHSML and RAPA on PHSML-SGB were observed. The results showed that PHSML, but not PHSML-SGB, incubation decreased VSMC contractility and induced autophagy activation and phenotype transformation. Importantly, 3-MA administration reversed the adverse effects of PHSML, and RAPA treatment attenuated the effects of PHSML-SGB incubation on VSMCs. Taken together, the protective effect of SGB on vascular reactivity is achieved by inhibiting excessive autophagy-mediated phenotypic transformation of VSMCs to maintain their contractile phenotype.
Invasive Hemodynamic Monitoring with Pulmonary Artery Catheter in Sepsis-associated Cardiogenic Shock
Authors: Sato Ryota , Hasegawa Daisuke , Guo Stephanie C. , Nishida Kazuki , Dugar Siddharth
Published: December 2023

Background

Both sepsis-induced cardiomyopathy and worsening of pre-existing cardiac disease can contribute to circulatory shock in septic patients, The early use of pulmonary artery catheter (PAC) could play a pivotal role in the management of sepsis-associated cardiogenic shock. In this study, we aimed to evaluate the impact of early invasive hemodynamic monitoring with PAC in patients with sepsis-associated cardiogenic shock.

Method

We performed a retrospective study using the National Inpatient Sample data from 01/2017 to 12/2019. The early use of PAC was defined as the use of PAC within 2 days from the admission. We performed the multivariable logistic regression analysis to investigate the association between the early use of PAC and in-hospital mortality in patients with sepsis-associated cardiogenic shock and sepsis without cardiogenic shock, respectively.

Results

There was no difference in in-hospital mortality between PAC and No PAC groups in sepsis without cardiogenic shock (adjusted odds ratio [aOR]: 1.05, 95% confidence interval [CI]: 0.82 – 1.35, p = 691). On the other hand, the early use of PAC was independently associated with lower in-hospital mortality in patients with sepsis-associated cardiogenic shock (aOR: 0.58, 95% confidence interval [CI]: 0.46 – 0.72, p < 0.001). The use of PAC was also associated with increased use of MCS in those with sepsis-associated cardiogenic shock (aOR: 12.26, 95% CI: 9.37 – 16.03, p < 0.001). For patients with sepsis-associated cardiogenic shock, the use of PAC after 2 days of admission was associated with significantly higher in-hospital mortality and decreased use of mechanical circulatory support.

Conclusion

The use of pulmonary artery catheters in sepsis-associated cardiogenic shock was associated with significantly lower in-hospital mortality and increased use of mechanical circulatory supports in patients with sepsis-associated cardiogenic shock.
PROGNOSTIC PERFORMANCE OF SERIAL DETERMINATION OF THE SOCIETY FOR CARDIOVASCULAR ANGIOGRAPHY AND INTERVENTIONS SHOCK CLASSIFICATION IN ADULTS WITH CRITICAL ILLNESS
Authors: Jentzer Jacob C. , Sanghavi Devang , Patel Parag C. , Bhattacharyya Anirban , van Diepen Sean , Herasevich Vitaly , Gajic Ognjen , Kashani Kianoush B.
Published: December 2023

Purpose:The aim of the study is to evaluate whether serial assessment of shock severity can improve prognostication in intensive care unit (ICU) patients.Materials and Methods:This is a retrospective cohort of 21,461 ICU patient admissions from 2014 to 2018. We assigned the Society for Cardiovascular Angiography and Interventions (SCAI) Shock Stage in each 4-h block during the first 24 h of ICU admission; shock was defined as SCAI Shock stage C, D, or E. In-hospital mortality was evaluated using logistic regression.Results:The admission SCAI Shock stages were as follows: A, 39.0%; B, 27.0%; C, 28.9%; D, 2.6%; and E, 2.5%. The SCAI Shock stage subsequently increased in 30.6%, and late-onset shock developed in 30.4%. In-hospital mortality was higher in patients who had shock on admission (11.9%) or late-onset shock (7.3%)versusno shock (4.3%). Persistence of shock predicted higher mortality (adjusted OR = 1.09; 95% CI = 1.06–1.13, for each ICU block with shock). The mean SCAI Shock stage had higher discrimination for in-hospital mortality than the admission or maximum SCAI Shock stage. Dynamic modeling of the SCAI Shock classification improved discrimination for in-hospital mortality (C-statistic = 0.64–0.71).Conclusions:Serial application of the SCAI Shock classification provides improved mortality risk stratification compared with a single assessment on admission, facilitating dynamic prognostication.
THE ROLE OF N6-METHYLADENOSINE METHYLTRANSFERASE RBM15 IN NONALCOHOLIC FATTY LIVER DISEASE
Authors: Li Shiqing , Lian Shengyi , Cheng Wei , Zhang Tao , Gong Xiaobing
Published: December 2023

Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disorder with significant health implications. N6-methyladenosine (m6A) methyltransferase is known to exert regulatory functions in liver-related diseases. This study investigates the intricate role of RNA binding motif protein 15 (RBM15) in modulating inflammation and oxidative stress in NAFLD. An NAFLD model was induced in mice (male, C57BL/6J, 72 mice in the sham group) through a high-fat diet for 9 weeks, and hepatocytes were exposed to long chain-free fatty acids. The expression levels of RBM15, ring finger protein 5 (RNF5), and rho-kinase 1 (ROCK1) were assessed. RBM15 expression was intervened (injection of AAV9 virus at week 9 and detection at week 11). Liver damage was evaluated using staining assays, along with assessments of weight changes and lipid levels. Notably, RBM15 (decreased approximately 40%/60%) and RNF5 (decreased approximately 60%/75%) were poorly expressed while ROCK1 (increased approximately 2.5-fold) was highly expressed in liver tissues and cells. RBM15 overexpression mitigated liver damage, inflammation, and oxidative stress in NAFLD mice, resulting in reduced liver-to-body weight ratio (20%) and decreased levels of alanine aminotransferase (54%), aspartate aminotransferase (36%), total cholesterol (30%), and triglycerides (30%), and inhibited inflammation and oxidative stress levels. Mechanistically, RBM15 upregulated RNF5 expression through m6A methylation modification, and RNF5 suppressed ROCK1 protein levels through ubiquitination modification. RNF5 knockdown or ROCK1 overexpression accelerated inflammation and oxidative stress in NAFLD. Taken together, RBM15 upregulated RNF5 expression through m6A methylation modification. RNF5 inhibited ROCK1 expression through ubiquitination modification to mitigate NAFLD.
Roadmap for modern development of Chinese medicine: Traditional, evidence-based, and digital-intelligent paths
Authors: Zhang Xiaoyu , Zhang Xiaowei , Li Xiao , Wang Shuangqiu , Zhao Chen , Chen Zhao , You Liangzhen , Jiang Yin , Lin Hongyuan , Wei Xuxu , Xiong Jun , Chen Xiaofan , Jin Yinghui , Xu Xue , Shang Hongcai
Published: December 2023

Accelerating the modernization of Chinese medicine (CM) is the focus of CM development in the new era. Looking back over the past 50 years, CM has progressed along traditional, evidence-based, and digital-intelligent paths. These paths have intertwined and mutually propelled the advancement of CM modernization. This article analyzes the patterns of 3 paths, summarizes the current status of CM development along these paths, and presents a vision for future development.
Antibiotic Stewardship in Dentistry: Evaluating the Impact of Outpatient Antibiotic Prophylaxis in a Tertiary Care Hospital Setting
Authors: Rajakumar Ratheesh , Dorairajan Suresh kumar , Banu Safiya , Mahesh Poojadharshini
Published: December 2023

Aim. To assess the antibiotic prophylaxis in the prescriptions of the patients attending the Dental Outpatient department in a Tertiary care hospital. Background. Antibiotics are most commonly used in outpatient setting when compared to inpatient setting in dental department. American Dental Association guidelines for antibiotic use for dental infections plays an important role in reducing prescribing for common conditions in dentistry. As there is no proper evidence regarding efficient use of antibiotic prophylaxis in dentistry, this study is aimed to address the prophylactic use of appropriate antibiotics among the outpatients in dental department. Methods. This Retrospective Observational study was conducted in the dental outpatient department in a tertiary care hospital for a month. The data regarding the Antibiotic prophylaxis along with underlying cardiac conditions were collected from records of the patients prescription and analysed using Simple statistics. Results. A total of 150 prescriptions (Male = 78 & Female = 72) are collected. Mean age was found to be 45.8 years (0 - 90). Most dental diagnosis are Scaling, Tooth extraction, Dental caries, Luting, Filling, Splint placing, Impacted tooth, Dental Abscess and Other Procedures. 88 prescriptions were found to have Antibiotic prophylaxis, where Amoxicillin is the most prescribed antibiotic. 2 days is the mostly prescribed duration of Antibiotic therapy. 13 Prescriptions had patients with underlying cardiac conditions who were prescribed with antibiotics prophylaxis. Conclusion. The antibiotic prescribing pattern in Dental outpatient department was assessed and it was found that 85% of patients were prescribed with antibiotics other than patients with underlying cardiac conditions. Keywords: Antibiotics, Antimicrobial stewardship, Prophylaxis, Prescribing patterns, Dental, Outpatients.
Genetic variants inDDX53contribute to Autism Spectrum Disorder associated with the Xp22.11 locus
Authors: Scala Marcello , Bradley Clarrisa A. , Howe Jennifer L. , Trost Brett , Salazar Nelson Bautista , Shum Carole , Reuter Miriam S. , MacDonald Jeffrey R. , Ko Sangyoon Y. , Frankland Paul W. , Granger Leslie , Anadiotis George , Pullano Verdiana , Brusco Alfredo , Keller Roberto , Parisotto Sarah , Pedro Helio F. , Lusk Laina , McDonnell Pamela Pojomovsky , Helbig Ingo , Mullegama Sureni V. ,   Undiagnosed Diseases Network, Douine Emilie D. , Russell Bianca E. , Nelson Stanley F. , Zara Federico , Scherer Stephen W.
Published: December 2023

Autism Spectrum Disorder (ASD) exhibits an ∼4:1 male-to-female sex bias and is characterized by early-onset impairment of social/communication skills, restricted interests, and stereotyped behaviors. Disruption of the Xp22.11 locus has been associated with ASD in males. This locus includes the three-exonPTCHD1gene, an adjacent multi-isoform long noncoding RNA (lncRNA) namedPTCHD1-AS(spanning ∼1Mb), and a poorly characterized single-exon RNA helicase namedDDX53that is intronic toPTCHD1-AS. While the relationship betweenPTCHD1/PTCHD1-ASand ASD is being studied, the role ofDDX53has not been examined, in part because there is no apparent functional murine orthologue. Through clinical testing, here, we identified 6 males and 1 female with ASD from 6 unrelated families carrying rare, predicted-damaging or loss-of-function variants inDDX53. Then, we examined databases, including the Autism Speaks MSSNG and Simons Foundation Autism Research Initiative, as well as population controls. We identified 24 additional individuals with ASD harboring rare, damagingDDX53variations, including the same variants detected in two families from the original clinical analysis. In this extended cohort of 31 participants with ASD (28 male, 3 female), we identified 25 mostly maternally-inherited variations inDDX53, including 18 missense changes, 2 truncating variants, 2 in-frame variants, 2 deletions in the 3’ UTR and 1 copy number deletion. Our findings in humans support a direct link betweenDDX53and ASD, which will be important in clinical genetic testing. These same autism-related findings, coupled with the observation that a functional orthologous gene is not found in mouse, may also influence the design and interpretation of murine-modelling of ASD.
HumanELY: Human evaluation of LLM yield, using a novel web-based evaluation tool
Authors: Awasthi Raghav , Mishra Shreya , Mahapatra Dwarikanath , Khanna Ashish , Maheshwari Kamal , Cywinski Jacek , Papay Frank , Mathur Piyush
Published: December 2023

Abstract

Large language models (LLMs) have caught the imagination of researchers,developers and public in general the world over with their potential for transformation. Vast amounts of research and development resources are being provided to implement these models in all facets of life. Trained using billions of parameters, various measures of their accuracy and performance have been proposed and used in recent times. While many of the automated natural language assessment parameters measure LLM output performance for use of language, contextual outputs are still hard to measure and quantify. Hence, human evaluation is still an important measure of LLM performance,even though it has been applied variably and inconsistently due to lack of guidance and resource limitations.

To provide a structured way to perform comprehensive human evaluation of LLM output, we propose the first guidance and tool called HumanELY. Our approach and tool built using prior knowledge helps perform evaluation of LLM outputs in a comprehensive, consistent, measurable and comparable manner. HumanELY comprises of five key evaluation metrics: relevance, coverage, coherence, harm and comparison. Additional submetrics within these five key metrics provide for Likert scale based human evaluation of LLM outputs. Our related webtool uses this HumanELY guidance to enable LLM evaluation and provide data for comparison against different users performing human evaluation. While all metrics may not be relevant and pertinent to all outputs, it is important to assess and address their use.

Lastly, we demonstrate comparison of metrics used in HumanELY against some of the recent publications in the healthcare domain. We focused on the healthcare domain due to the need to demonstrate highest levels of accuracy and lowest levels of harm in a comprehensive manner. We anticipate our guidance and tool to be used for any domain where LLMs find an use case.

Link to the HumanELY Tool

https://www.brainxai.com/humanely
Nowcasting Reported COVID-19 Hospitalizations Using De-Identified, Aggregated Medical Insurance Claims Data
Authors: Shen Xueda , Rumack Aaron , Wilder Bryan , Tibshirani Ryan J.
Published: December 2023

We propose, implement, and evaluate a method for nowcasting the daily number of new COVID-19 hospitalizations, at the level of individual US states, based on de-identified, aggregated medical insurance claims data. Our analysis proceeds under a hypothetical scenario in which, during the Delta wave, states only report data on the first day of each month, and on this day, report COVID-19 hospitalization counts for each day in the previous month. In this hypothetical scenario (just as in reality), medical insurance claims data continues to be available daily. At the beginning of each month, we train a regression model, using all data available thus far, to predict hospitalization counts from medical insurance claims. We then use this model to nowcast the (unseen) values of COVID-19 hospitalization counts from medical insurance claims, at each day in the following month. Our analysis uses properly-versioned data, which would have been available in real-time at the time predictions are produced (instead of using data that would have only been available in hindsight). In spite of the difficulties inherent to real-time estimation (e.g., latency and backfill) and the complex dynamics behind COVID-19 hospitalizations themselves, we find altogether that medical insurance claims can be an accurate predictor of hospitalization reports, with mean absolute errors typically around 0.4 hospitalizations per 100,000 people, i.e., proportion of variance explained around 75%. Perhaps more importantly, we find that nowcasts made using medical insurance claims are able to qualitatively capture the dynamics (upswings and downswings) of hospitalization waves, which are key features that inform public health decision-making.
Impaired activation of the prefrontal executive network during working memory processing in multiple sclerosis
Authors: Rossi Chiara , Vidaurre Diego , Costers Lars , D’hooghe Marie B , Akbarian Fahimeh , D’haeseleer Miguel , Woolrich Mark , Nagels Guy , Schependom Jeroen Van
Published: December 2023

Abstract

In multiple sclerosis (MS), working memory (WM) impairment occurs soon after disease onset and significantly affects the patient’s quality of life. Functional imaging research in MS aims to investigate the neurophysiological underpinnings of WM impairment. In this context, we utilized a data-driven technique, the time delay embedded- hidden Markov model (TDE-HMM), to extract spectrally defined functional networks in magnetoencephalographic (MEG) data acquired during a WM visual-verbal n-back task. We observed that two networks show an altered activation in RR-MS patients. First, the activation of an early theta prefrontal network linked to stimulus encoding and attentional control significantly decreased in RR-MS compared to HC. This diminished activation correlated with reduced accuracy in task performance in the MS group, suggesting an impaired encoding and learning process. Secondly, a frontoparietal network characterized by beta coupling is activated between 300 and 600 ms after stimulus onset; this resembles the characteristic event-related P300, a cognitive marker extensively explored in EEG studies. The activation of this network is amplified in patients treated with benzodiazepine, in line with the well-known benzodiazepine-induced beta enhancement. Altogether, the TDE-HMM technique extracted task-relevant functional networks showing disease-specific and treatment- related alterations, revealing potential new markers to assess and track WM impairment in MS.

Highlights

We decomposed the brain dynamics underlying a WM n-back task in data-driven, spectrally defined whole-brain networks in both healthy controls and people with relapsing-remitting-MS (pwMS).

PwMS showed a significantly decreased activation of an early theta prefrontal network linked to stimulus encoding and attentional control.

The weaker activation of this prefrontal theta network is correlated with worse task performance.

A beta frontoparietal network with a P300-like temporal evolution was significantly modulated by the use of benzodiazepines.

The model distinguished disease-induced and treatment-induced dynamic network alterations.
Rationally designed modular STAT-activating scaffolds enforce cell-intrinsic transcriptional programs augmenting the anti-tumor potency of CAR T cells
Authors: Saxby Christopher P , Ishida Taylor K , Rosser James M , Curtis Benjamin C , Baldwin Michael L , Spurrell Cailyn H , Giles Justin , Valdez Ardizon , Gustafson Joshua , Johnson Adam J , Appelbaum Jacob S , Jensen Michael C
Published: December 2023

Chimeric antigen receptor (CAR)-expressing T cells can mediate anti-tumor responses in a variety of preclinical models and clinical settings, however, strategies to enhance anti-tumor potency is the subject of intense investigation. Signals emanating from gamma-c cytokine receptors modulate the transcriptional state of activated T cells impacting proliferation, survival, differentiation, and effector functioning through the STAT family of transcription factors. Design of ligand-independent cell-intrinsic cytokine STAT activation scaffolds is a conceptually attractive strategy to provide CAR T cells with a surrogate for exogenous cytokine support. Here, we designed a series of ligand-autonomous STAT inducer (LASI) scaffolds comprised of an extracellular identification tag, a homodimerizing transmembrane domain, and a membrane proximal IL7R Box1 domain followed by STAT5 and/or STAT3 docking sequences derived from IL7R and IL21R, respectively. We constructed LASI scaffolds having STAT5 (LASI-5), STAT3 (LASI-3), and combined STAT5 and STAT3 (LASI-5+3) docking domains and then interrogated their impact in primary human CD8+anti-CD19 (4-1BB:zeta) CAR T cells. While LASI-5 expression had limited effects on CAR T cells, LASI-3 transcriptional programming was found to be indispensable to achieving anti-tumor functional enhancement associated with limited terminal differentiation, heightened T cell proliferation in response to antigen, and dampened expression of exhaustion-associated genes. Moreover, CAR T cells supplemented with LASI-3 or 5+3 displayed superior potency against human leukemia tumors in NSG mice. LASI-5+3 mediated the highest magnitude of CAR T cell engraftmentin vivothat evolved into a fatal lymphoproliferative syndrome. However, the same efficacy enhancement was achieved with LASI-3 without the lymphoproliferative complication. Our findings provide a rationale for utilization of constitutively expressed LASI-3 to enhance the anti-tumor potency of CAR T cells, the need to regulate the activity of LASI-5+3, and a generalizable scaffold design for studying additional combinations of STAT family transcription factors.
Assessing the Ability of GPT to Generate Illness Scripts: An Evaluation Study
Authors: Yanagita Yasutaka , Yokokawa Daiki , Fukuzawa Fumitoshi , Uchida Shun , Uehara Takanori , Ikusaka Masatomi
Published: December 2023

Background

Illness scripts, which are structured summaries of clinical knowledge concerning diseases, are crucial in disease prediction and problem representation during clinical reasoning. Clinicians iteratively enhance their illness scripts through their clinical practice. Because illness scripts are unique to each physician, no systematic summary of specific examples of illness scripts has been reported.

Objective

Generative artificial intelligence (AI) stands out as an educational aid in continuing medical education. The effortless creation of a typical illness script by generative AI could enhance the comprehension of disease concepts and increase diagnostic accuracy. This study investigated whether generative AI possesses the capability to generate illness scripts.

Methods

We used ChatGPT, a generative AI, to create illness scripts for 184 diseases based on the diseases and conditions integral to the National Model Core Curriculum for undergraduate medical education (2022 revised edition) and primary care specialist training in Japan. Three physicians applied a three-tier grading scale: “A” if the content of each disease’s illness script proves sufficient for training medical students, “B” if it is partially lacking but acceptable, and “C” if it is deficient in multiple respects. Moreover, any identified deficiencies in the illness scripts were discussed during the evaluation process.

Results

Leveraging ChatGPT, we successfully generated each component of the illness script for 184 diseases without any omission. The illness scripts received “A,” “B,” and “C” ratings of 56.0% (103/184), 28.3% (52/184), and 15.8% (29/184), respectively.

Conclusion

Useful illness scripts were seamlessly and instantaneously created by ChatGPT using prompts appropriate for medical students. The technology-driven illness script is a valuable tool for introducing medical students to disease conceptualization.
Nitrogen availability and TOR signalling are important for preventing catastrophic mitosis in fission yeast
Authors: Zemlianski Viacheslav , Marešová Anna , Princová Jarmila , Holič Roman , Häsler Robert , del Río Manuel José Ramos , Lhoste Laurane , Zarechyntsava Maryia , Převorovský Martin
Published: December 2023

Mitosis is a critical stage in the cell cycle, controlled by a vast network of regulators responding to multiple internal and external factors. The fission yeastSchizosaccharomyces pombemay demonstrate catastrophic mitotic phenotypes due to mutations or drug treatments. One of the factors provoking catastrophic mitosis is a disturbed lipid metabolism, resulting from e.g. mutations in acetyl-CoA/biotin carboxylase (cut6), in fatty acid synthase (fas2/lsd1), or in the transcriptional regulator of lipid metabolism (cbf11) genes, as well as treatment with inhibitors of fatty acid synthesis. It was previously shown that mitotic fidelity in lipid metabolism mutants can be partially rescued by ammonium chloride. In this study we demonstrate that mitotic fidelity can be improved by multiple good nitrogen sources. Moreover, this rescue is not limited to lipid metabolism disturbances but also applies to a number of unrelated mitotic mutants. Interestingly, the rescue is not achieved by restoring the lipid metabolism state, but rather indirectly. We found that the TOR regulatory network plays a major role in mediating such rescue, highlighting a novel role for TOR in mitotic fidelity.
Climate Change and Phenological Monitoring of the Indigenous Godello Variety in a Territory of Heroic Viticulture and Biosphere Reserve
Authors: Fernandez-Conde Mª Eva , Bisarya Dipti , Taglinao Liwayway Perlado , Cortiñas J. Antonio
Published: December 2023

An evaluation of the phenological behaviour of the indigenous Godello variety of vineyard was conducted within the Souto Chao plot in the year 2023. This plot is located in a wine-growing region holding a Designation of Origin (Ribeira Sacra DO) located in the North-West of the Iberian Peninsula. A similar study had been conducted in 2017 and 2018, focusing on the same Godello variety within the identical plot involving the same plant as the current study.

The assessment utilized the BBCH scale, a system proposed byBiologische Bundesanstalt für Land und Forstwirtschaft, Bundessortenamt und CHemische Industrie.

The average duration of the vegetative cycle in the initial two years under examination was 167 days (161 and 174 days in 2017 and 2018, respectively), while in 2023 it was 164 days. In these three years studies during 2017, 2018 and 2023, the longest phenological phase was of 79 days when majority of the berries were touching).

The primary objective of this study is to ascertain the nature and extent of changes in the crop’s phenology within the timeframe between the initial two years analysed (2017 and 2018) and the present year, 2023.
Coupling Cell Size Regulation and Proliferation Dynamics ofC. glutamicumReveals Cell Division Based on Surface Area
Authors: Nieto César , Täuber Sarah , Blöbaum Luisa , Vahdat Zahra , Grünberger Alexander , Singh Abhyudai
Published: December 2023

Single cells actively coordinate growth and division to regulate their size, yet how this size homeostasis at the single-cell level propagates over multiple generations to impact clonal expansion remains fundamentally unexplored. Classicaltimermodels for cell proliferation (where the duration of the cell cycle is an independent variable) predict that the stochastic variation in colony size will increase monotonically over time. In stark contrast, implementing size control according toadderstrategy (where on average a fixed size added from cell birth to division) leads to colony size variations that eventually decay to zero. While these results assume a fixed size of the colony-initiating progenitor cell, further analysis reveals that the magnitude of the intercolony variation in population number is sensitive to heterogeneity in the initial cell size. We validate these predictions by tracking the growth of isogenic microcolonies ofCorynebacterium glutamicumin microfluidic chambers. Approximating their cell shape to a capsule, we observe that the degree of random variability in cell size is different depending on whether the cell size is quantified as per length, surface area, or volume, but size control remains an adder regardless of these size metrics. A comparison of the observed variability in the colony population with the predictions suggests that proliferation matches better with a cell division based on the cell surface. In summary, our integrated mathematical-experimental approach bridges the paradigms of single-cell size regulation and clonal expansion at the population levels. This innovative approach provides elucidation of the mechanisms of size homeostasis from the stochastic dynamics of colony size for rod-shaped microbes.
Neural entrainment to both target and distracting speech causally contributes to speech perception in a multi-speaker scenario
Authors: Erkens Jules , Marx Mathieu , Zoefel Benedikt
Published: December 2023

Segregating important stimuli from distractors is crucial for successful speech perception. Neural activity aligned to speech, also termed “neural entrainment”, is thought to be instrumental for this purpose. However, the relative contribution of neural entrainment to target and distractors in speech perception remained unclear. In this study, we used transcranial alternating current stimulation (tACS) to manipulate entrainment to two simultaneously presented sequences of rhythmic speech while participants attended to one of them. A random temporal relationship between speech streams allowed us to disentangle effects of tACS on target and distractor processing, and to examine their combined effect on a behavioural measure of speech perception. We found that the phase relation between tACS and both target and distracting speech modulated word report accuracy, and to a similar degree. The phasic modulation of target processing correlated with that of the distractor across subjects, and their combined effect on speech perception was stronger than each of the two alone. In contrast to our expectation, the tACS phases leading to most accurate perception were uncorrelated between target and distracting speech modulations. Together, our results suggest that entrainment to target and distracting speech jointly and causally contributes to speech perception. They also demonstrate how effect sizes might be increased in future work and for technological or clinical applications.

Significance statement

Synchronising neural activity to moments of important information in speech is beneficial for its perception. Successful speech perception is a consequence of both target processing and the suppression of potential distractors; so far, it has remained unclear whether brain-speech synchronisation plays a more important role for either of these two tasks. We used transcranial brain stimulation (tACS) in a multi-speaker scenario to independently manipulate synchronisation to target- or distracting speech, respectively. We found that both manipulations led to changes in speech perception that were of comparable magnitude, and their combined effect was stronger than either of them alone. These results give an insight into the cortical processing of competing speech streams and how brain-speech synchronisation causally contributes to their perception. Our findings also have implications for practical applicability of brain stimulation protocols, showing how they could be used and made more effective in improving speech perception. This approach could have potential for medical application such as additional support in hearing aids.