bluuebunny/crossref_metadata_2025 huggingface dataset:
Be a Good Observer
Authors: Friedland Robert P.
Published: January 2025

Being a good observer is often more important than being exceptionally knowledgeable. The patient is trying to teach you what the problem is.
Learn from Your Patients
Authors: Friedland Robert P.
Published: January 2025

Be willing to learn what the patient has to teach you.
Be Prepared for the Unexpected
Authors: Friedland Robert P.
Published: January 2025

Although rare events are uncommon they do occur. Be prepared.
Treat the Patient, Not the Test
Authors: Friedland Robert P.
Published: January 2025

Decisions in regard to patient care should be made based on the patient's condition, not solely on the laboratory tests. Treat the patient not the test.
Consider Toxic Exposures
Authors: Friedland Robert P.
Published: January 2025

Toxic exposures mimic disorders of vascular, neoplastic or genetic origin (or others).
Family History Is an Important Part of the Interview
Authors: Friedland Robert P.
Published: January 2025

A comprehensive family history can often be very helpful in patient evaluation.
Get to Know the Patient and Show Interest (the Patient Is a Person)
Authors: Friedland Robert P.
Published: January 2025

Awareness of the patient and of how physicians learn from them and how patients learn from their physicians is crucial. Physicians need to learn about their patients so that they can make proper decisions about their care. Patients perceive their caregivers’ attitudes, and this influences their ability to follow directions. It is important to be aware of the patient’s point of view, which may be influenced by denial, deficits in cognitive function, poor understanding, and bias. Denial can be implicit or explicit and can profoundly influence all aspects of healthcare. The context of care, considering the patient's life circumstances and environment, may greatly influence health. It is hazardous to focus attention on disease causation, disease mechanisms, medications, and laboratory tests if attention to the patient is lost.
Use the Placebo Response to Your Patient’s Benefit
Authors: Friedland Robert P.
Published: January 2025

Placebo effects are responsible for over 1/3 of all drug effects.
Cognitive Function Is Relevant for All Areas of Medicine
Authors: Friedland Robert P.
Published: January 2025

All medical practitioners need to be able to assess cognitive function.
Consider the Context of Care
Authors: Friedland Robert P.
Published: January 2025

The needs of the patient must be considered in regard to the biopsychosocial context of their life.
Challenges to the Ability to Provide Humane Healthcare
Authors: Friedland Robert P.
Published: January 2025

The needs of the patient must not be obscured by excessive data and focus on laboratory investigations.
Be Attentive to Medications and Medication Errors
Authors: Friedland Robert P.
Published: January 2025

Medication errors are a major cause of sickness and death throughout the world.
Think Deeply (Think Beyond the Obvious)
Authors: Friedland Robert P.
Published: January 2025

Critical thinking describes the ability to analyze information, make judgments, ask questions, and plan actions. Many decisions in healthcare and science are made on “auto-pilot” without thinking deeply about causes and consequences of actions. Logical analysis can be assisted by respect for intuition and by understanding the many forms of bias which influence judgment. Disease models may be helpful in research efforts as long as the models’ assumptions are considered. Biomarkers may also be valuable, but their limitations must not be overlooked. Progress in science is not linear, and theories about patients and scientific problems may be incomplete but still valuable. Success in research and in research careers is most often a product of hard work and not brilliance. Respect for the evolutionary origin of human cognition and perception can help enhance the capacity for understanding complex problems. Remember that one does not need to think “out of the box.” One needs to realize that there is no box.
Although Intuition Cannot Replace Evidence, It Can Be Valuable
Authors: Friedland Robert P.
Published: January 2025

Intuition may be a valuable aid to decision making.
Biomarkers Are Not the Disease Itself
Authors: Friedland Robert P.
Published: January 2025

Biomarkers may be helpful but they must be considered in the context of the patient's life.
Fishing Expeditions May Be Productive
Authors: Friedland Robert P.
Published: January 2025

It is not necessary to have a hypothesis for every research endeavor.
Bias of the Lost Actors
Authors: Friedland Robert P.
Published: January 2025

Our experience is limited to information and interactions which we have accomplished. Survivorship bias, also called the bias of the lost actors, describes how we do not experience outcomes which are not available to us.
Learn to Critically Read the Literature
Authors: Friedland Robert P.
Published: January 2025

Much of what is published is wrong. It is vital to learn how to critically review the literature.
We Are All Neurologists
Authors: Friedland Robert P.
Published: January 2025

In order to succeed in school we need to learn how our own brain works. The endeavor to learn how we learn is of great importance.
Do Not Respect Boundaries, Be a Trespasser
Authors: Friedland Robert P.
Published: January 2025

Looking into new fields without extensive previous experience can be very valuable.
Focus, but Not Too Much
Authors: Friedland Robert P.
Published: January 2025

Although focus is important for research success it is also vital to be aware of progress in other fields.
You Are An Educator—That’s One of Your Most Important Responsibilities
Authors: Friedland Robert P.
Published: January 2025

All persons working in medicine and science need to be educators.
No Single Theory Ever Agrees with All the Facts
Authors: Friedland Robert P.
Published: January 2025

If you have an idea that is contradicted by a fact that does not mean the idea must be wrong.
It’s Good To Be First, but It Is Not Necessary
Authors: Friedland Robert P.
Published: January 2025

It is desirable but not necessary for scientific advances to be completely original.
Judge Every Project by Asking “What Difference Will It Make To Know the Answer?”
Authors: Friedland Robert P.
Published: January 2025

Before a research project is undertaken it is worth considering what difference it will make to know the answer.
Be Aware of (Beware of   ) Statistics and Data Torturing
Authors: Friedland Robert P.
Published: January 2025

Avoid excessive statistical analysis and remember that correlations do not imply causation.
You Can Make Contributions as a Clinician Without a Laboratory
Authors: Friedland Robert P.
Published: January 2025

Careful clinical observations can lead to great advances.
Advancing personalized cancer therapy: Onko_DrugCombScreen—a novel Shiny app for precision drug combination screening
Authors: Yang Jingyu , Wang Meng , Dönitz Jürgen , Chapuy Björn , Beißbarth Tim
Published: January 2025

Identifying and validating genotype-guided drug combinations for a specific molecular subtype in cancer therapy represents an unmet medical need and is important in enhancing efficacy and reducing toxicity. However, the exponential increase in combinatorial possibilities constrains the ability to identify and validate effective drug combinations. In this context, we have developed Onko_DrugCombScreen, an innovative tool aiming at advancing precision medicine based on identifying significant drug combination candidates in a target cancer cohort compared to a comparison cohort. Onko_DrugCombScreen, inspired by the molecular tumor board process, synergizes drug knowledgebase analysis with various statistical methodologies and data visualization techniques to pinpoint drug combination candidates. Validated through a TCGA-BRCA case study, Onko_DrugCombScreen has demonstrated its proficiency in discerning established drug combinations in a specific cancer type and in revealing potential novel drug combinations. By enhancing the capability of drug combination discovery through drug knowledgebases, Onko_DrugCombScreen represents a significant advancement in personalized cancer treatment by identifying promising drug combinations, setting the stage for the development of more precise and potent combination treatments in cancer care. The Onko_DrugCombScreen Shiny app is available at https://rshiny.gwdg.de/apps/onko_drugcombscreen/. The Git repository can be accessed at https://gitlab.gwdg.de/MedBioinf/mtb/onko_drugcombscreen.
Chemical Constituents and Particle Size Distribution of Mainstream Emission from Electronic Waterpipe
Authors: Klupinski Theodore P , Adetona Anna , Ivanov Alexander , Richardson Aaron , Strozier Erich D , Aume Laura L S , Karam Hani , Makselan Stephanie D , McCauley Martha , Mullins Larry , Stiffler Billie , Lucas Eric A , Kim Hyoshin
Published: January 2025

Introduction

An electronic waterpipe (electronic hookah) uses an electronic heating element to promote the vaporization and aerosolization of an e-liquid in a waterpipe. There is little or no published information characterizing the toxicant levels or particle size distributions of electronic waterpipe mainstream emission.

Methods

Controlled laboratory experiments were performed to evaluate electronic waterpipe mainstream emission for 40 test conditions: 10 e-liquid products × 2 power settings × 2 puffing topographies. Data were collected for amounts of three volatile toxicants and selected semi-volatile compounds, mass of total particulate matter, and particle size distribution within the size range of 5–1000 nm.

Results

Amounts of the volatile toxicants acetaldehyde, acrolein, and benzene measured in mainstream emission were 33–505 µg/session, 27–415 µg/session, and 0.69–2.44 µg/session, respectively. The amounts of acetaldehyde and acrolein, when reported in units of µg/puff, are generally similar to some literature-reported amounts in e-cigarette mainstream emission and tobacco waterpipe smoke. A bimodal or trimodal particle size distribution was typically observed, and substantial concentrations of nanoparticles were detected. The amounts (in µg/puff) of the volatile toxicants and several quantitative measures of particle size distribution were significantly affected by power setting and puffing topography.

Conclusions

Given the hazards of acetaldehyde and acrolein and the distinctive toxicological profile of nanoparticles, electronic waterpipe use may present significant toxicity concerns. Operation of an electronic waterpipe is a complex process in which physics, fluid dynamics, and chemistry interact to yield mainstream emission for which the composition is sensitive to changes from various sources.

IMPLICATIONS

This publication, to our knowledge, is the first to report the amounts of toxicants and particle size distributions in electronic waterpipe mainstream emission. The results reported herein suggest that there may be significant toxicity concerns associated with electronic waterpipe use as indicated by the levels of volatile toxicants and the presence of nanoparticles in electronic waterpipe mainstream emission. This knowledge is valuable to support the research community and tobacco regulatory agencies in understanding the impact that electronic waterpipe use may have on public health.
Asset Pricing in the Information Age: Employee Expectations and Stock Returns
Authors: Sheng Jinfei
Published: January 2025

Firms with more positive employee expectations tend to earn higher future returns, delivering annualized abnormal returns ranging from 8% to 11%. Employees’ forward-looking expectations are a stronger return predictor than employee satisfaction, which is backward-looking. Employee expectations can predict returns because they reflect information about firms’ fundamentals that has not yet been reflected in traditional data sources, such as earnings reports. Hedge funds actively trade on this information, consistent with a decay in forecasting power over longer holding horizons. Overall, this paper highlights the importance of labor in asset pricing, specifically from the perspective of employee expectations. (JEL G12, G14)
Towards the definition of disease phenotypes in pediatric SAPHO syndrome: a national multicentric study
Authors: Matucci-Cerinic Caterina , Attico Anna , Malattia Clara , Consolaro Alessandro , Rosina Silvia , Breda Luciana , La Bella Saverio , Cattalini Marco , Ricci Francesca , Conti Giovanni , Civino Adele , Baldini Letizia , Licciardi Francesco , Insalaco Antonella , La Torre Francesco , Pastore Serena , Filocamo Giovanni , Beretta Gisella Beatrice , Biscaro Francesca , Miniaci Angela , Simonini Gabriele , Marrani Edoardo , Pistorio Angela , Ruperto Nicolino , Volpi Stefano , Caorsi Roberta , Viglizzo Gianmaria , Gattorno Marco ,   on behalf of REUMAPED
Published: January 2025

Objectives

To confirm the presence of different disease phenotypes of pediatric SAPHO syndrome (pSAPHO) based on their skin manifestations in a large cohort of Italian patients.

Methods

pSAPHO were enrolled in the Eurofever Registry and the data retrospectively analysed. Patients were divided depending on their skin manifestations into an Acne-Hidradenitis suppurativa (HS) group and a Palmoplantar Pustulosis-Psoriasis Vulgaris (PPP-PV) group and were compared with patients without skin manifestations (chronic non-bacterial osteomyelitis, CNO). Comparison of frequencies between groups was performed by the means of χ2 test or by Fischer’s Exact test.

Results

54 pSAPHO with skin manifestations (35 acne-HS, 19 PPP-PV) were enrolled and compared with 167 CRMO. In the Acne-HS, 82.9% were males, in the PPP-PV, 84.2% were females, while in the CNO group there were no gender differences (p< 0.0001). The 3 groups differed significantly for age at disease onset: acne-HS median 13.3 years, PPP-PV median 10.2 years, CNO median 9.5 years (p= 0.0001). An axial pattern was more frequent in acne-HS (91.4%) and PPP-PV group (89.4%) compared with CNO (46%) (p< 0.0001). Both acne-HS (82.9%), and PPP-PV (63.2%) required more frequently a biologic therapy than CNO (36.8%), but acne-HS presented a refractory skin disease requiring steroids and different lines of treatment, while PPP-PV responded well to biologics.

Conclusions

Our data have identified two different phenotypes of pSAPHO based on skin manifestations, with different sex, age and response to treatments. These two groups have peculiar clinical features different from the CNO group. A new classification encompassing these phenotypes is warranted.
Disparities in unmet need for family planning: a comparative study of urban and rural women in Kano State, Nigeria
Authors: Ibinaiye Taiwo , Adelekan Babatunde , Bajoga Ummulkhulthum , Ezikeanyi Sampson , Chijide Joachim , Opiyo Collins , Dasogot Andat , Kuawu Koessan
Published: January 2025

This study investigated urban–rural differences in the prevalence of unmet need for family planning among women of reproductive age in Kano State, Nigeria, and identified factors contributing to these disparities. Rural–urban disparities in unmet need for family planning outcomes and women’s characteristics were assessed. Univariate multilevel mixed-effect logistic regression models were employed to quantify the association between rural/urban residences and each unmet need for family planning and related outcomes. In urban areas, factors associated with unmet need for family planning included husband/partner (OR: 0.25, 95% CI 0.07 to 0.88, p=0.031) and joint decision-making about medical treatment (OR: 0.27, 95% CI 0.09 to 0.80, p=0.018). In rural areas, middle wealth categories (OR: 1.92, 95% CI 1.07 to 3.47, p=0.029), women with 3–4 (OR: 5.41, 95% CI 1.07 to 27.1, p=0.040) and ≥5 birth events (OR: 8.44, 95% CI 1.74 to 40.82, p=0.008) and those who work but are not paid in cash (OR: 0.46, 95% CI 0.21 to 0.99, p=0.049) were associated with unmet need for family planning. Tailored interventions considering socioeconomic, cultural and geographical factors are essential to reduce barriers to family planning services and promote informed decision-making among women in Kano State.
The Changes of Lymphocytes and Immune Molecules in Irradiated Mice by Different Doses of Radiation
Authors: Yang Tingyu , Gao Rong , Gao Yehui , Huang Mingyue , Cui Jialu , Lin Lin , Cheng Hongbo , Dang Wanyun , Gao Yue , Ma Zengchun
Published: January 2025

The effects of different radiation doses on T and B lymphocyte functional subsets and the changes of immune cells and immune molecules were observed in mice at different times post-irradiation to provide a theoretical basis for the changes of immune cells affected by radiation. In this study, the changes of T and B immune cells and immune-related molecules were observed at 1, 3, 7, 14, and 21 d after single irradiation of 2 Gy, 4 Gy, and 6 Gy. The results showed that white blood cells (WBC), lymphocytes (LYMPH), and lymphocyte percentage (LYMPH%) in peripheral blood of mice were significantly reduced and reached the lowest point 3 d after irradiation. Flow cytometry results showed that the percentages of CD3+T and CD8+/CD3+T lymphocytes in spleen and thymus were significantly decreased, and the percentages of CD19+B lymphocytes in spleen and CD4+/CD3+T lymphocytes in thymus were also decreased. However, the percentages of splenic NK cells, CD4+/CD3+T cells, and CD4+/CD8+ ratios in spleen and thymus were increased. Most of the indicators fell to the lowest or highest point 3 d after irradiation, indicating that immune function was suppressed at this time. From 7 to 21 d after irradiation, most immune cells gradually recovered. Single irradiation of 2 Gy, 4 Gy, and 6 Gy increased the contents of IL-1β, IL-2, IL-6, IL-17, TNF-α, TGF-β, and IFN-γ in serum of mice and decreased the contents of anti-inflammatory factors IL-4 and IL-10. The serum levels of immunoglobulin IgA, IgG, IgM and complement C3, C4 were significantly increased after irradiation. Our study showed that a single dose of 2 Gy, 4 Gy, and 6 Gy induced immunosuppression in mice, and maximum immunosuppression was achieved 3 d after irradiation. At this time, CD19+B lymphocytes were the most sensitive, followed by CD3+T lymphocytes, and NK cells were the most resistant. The radiosensitivity of CD8+/CD3+T lymphocytes was slightly higher than that of CD4+/CD3+T lymphocytes.
Nutrition in the critically ill in resource-limited settings/low- and middle-income countries
Authors: Mer Mervyn , Dünser Martin W.
Published: January 2025

Purpose of review

To share current concepts and provide an overview of the contextual issues and nutrition practices in critically ill patients in resource-limited settings (RLSs)/low- and middle-income countries (LMICs). Most of the world's population reside in these settings which also carries the greatest burden of critical illness.

Recent findings

There is a paucity of evidence on nutrition practice in critically ill patients in RLSs and international guidelines are largely based on evidence derived from high-income countries (HICs). While some recommendations are adaptable to RLSs, many are not feasible or directly transferable. Despite the challenges that may prevail, pragmatic solutions can address many of the difficulties to enhance nutrition practice and improve patient outcomes.

This review provides a contemporary synopsis of nutrition practice in critically ill patients in RLSs covering the relevance of optimal nutrition, gives insights into relevant contextual issues and challenges in RLSs, evaluates recent scientific evidence and available literature pertinent to critically ill patients in RLSs, addresses nutrition guidelines, discusses some pragmatic options and solutions, deals with relevant and important complications that may arise, and offers suggestions and future considerations to enhance nutrition practice in critically ill patients in these settings.
Ubiquitous microbial contaminants associated with scientific ocean drilling
Authors: Labonte Jessica , Campbell Kathryn L. , Walker Jordan R. , Rodriguez-Pilco Milena A.
Published: January 2025

Deep-sea subsurface samples typically have low microbial biomass, making them more susceptible to contamination. Potential contaminants can be introduced during any step of the scientific process, including drilling (contamination from the drilling fluid and lubricants, seawater), sample preparation (contamination from air and human handling), and DNA extraction, amplification, and sequencing (contamination from reagents). International Ocean Discovery Program (IODP) samples that are dedicated for microbiological analyses (known as MBIO samples) are routinely tested for contamination by injecting known concentrations of fluorescent microspheres or tracers directly into the drilling fluids. These tracers are a great tool to determine the level of drilling fluid contamination on board, but they are not consistently used and contamination of the samples could occur during other steps of sample processing and analysis. Moreover, there is an increased risk of contamination dominating the results of microbial surveys using polymerase chain reaction (PCR) amplification of marker genes. Here, we built a database of common contaminants through the screening of contamination controls from available 16S rRNA gene amplicon datasets from past IODP expeditions. These controls included various lubricants used on board, drilling fluids, seawater, DNA extraction blanks, and PCR blanks. The order Burkholderiales dominated most of the very low biomass samples, including negative controls, indicating the order’s ubiquity and its potential to be overamplified with common 16S rRNA amplification protocols. We amplified the 16S rRNA gene from preserved IODP legacy microbiological core samples and tested their level of contamination using the database. We also looked at published studies that did not sequence negative controls. Our results demonstrate that the type of drilling, amount of manipulation of the sample prior to preservation, and sample depth, often associated with biomass, can influence the level of contamination within subsurface samples. This work provides an analysis framework for microbial taxonomic survey studies from low biomass subsurface samples for future scientific ocean drilling expeditions.
Source Reconstruction Without an MRI using Optically Pumped Magnetometer based Magnetoencephalography
Authors: Rhodes Natalie , Rier Lukas , Boto Elena , Hill Ryan , Brookes Matthew J.
Published: January 2025

Source modelling in magnetoencephalography (MEG) maps the spatial origins of electrophysiological signals in the brain. Typically, this requires an anatomical MRI scan of the subject’s head, from which a model of the neuromagnetic field (the forward model) is derived. Wearable MEG – based on optically pumped magnetometers (OPMs) – enables MEG measurement from participants who struggle to cope with conventional scanning environments (e.g. children), enabling study of novel cohorts. However, its value is limited if an MRI scan is still required for source modelling. Here we describe a method of warping template MRIs to 3D structured-light scans of the head, to generate “pseudo-MRIs”. We apply our method using data from 20 participants during a sensory task, measuring induced (beta band) responses and whole-brain functional connectivity. Results show that the group average locations of peak task-induced beta modulation were separated by 2.75 mm, when comparing real- and pseudo-MRI approaches. Group averaged time-frequency spectra were also highly correlated (Pearson correlation 0.99) as were functional connectome matrices (0.87), and global connectivity (0.98). In sum, our results demonstrate that source-localized OPM-MEG data, modelled with and without an individual MRI scan can be similar. This will be useful for future studies where MRI data capture is challenging.
Glycaemic variability underlies myocyte dysfunction and myocardial injury risk in diabetes
Authors: Cao Yuanzhao , Redd Meredith A. , Outhwaite Jennifer E. , Mizikovsky Dalia , Shim Woo Jun , Fang Chen , Wu Zhixuan , Daygon Dara , Stark Terra , Palfreyman Robin , Chiu Han Sheng , Tan Clarissa , Thomas Ulrich , Dragicevic Elena , Sng Julian , Barrett Helen , Dorey Emily , Shah Sonia , Short Kirsty R. , Palpant Nathan J.
Published: January 2025

Heart disease is the leading cause of morbidity and mortality in individuals with diabetes, due largely to risks associated with ischaemic injuries such as myocardial infarction (MI). We use human population genetic data to demonstrate that current biomarkers of hyperglycaemia do not account for risk of post-MI mortality in diabetes patients. This study therefore systematically evaluates glycaemic stress underpinning cardiovascular risk in diabetes. Usingin vivoandin vitromodels, we demonstrate that glycaemic variability rather than hyperglycaemia alone is a dominant risk factor for heart muscle dysfunction and myocardial injury sensitivity in diabetes. These findings provide new preclinical models for mechanistic and drug discovery studies and inform strategies for managing cardiovascular outcomes in patients with diabetes.
Cotyledon opening during seedling deetiolation is determined by ABA-mediated splicing regulation
Authors: Martín Guiomar , Larran Alvaro , Qüesta Julia , Duque Paula
Published: January 2025

During seedling deetiolation, plants adjust their development to expose photosynthetic tissues to sunlight, enabling the transition from heterotrophic to autotrophic growth. While various plant hormones are known to influence this process, the role of abscisic acid (ABA) remains unclear. Here, we reveal that ABA plays a major role in controlling the dynamics of cotyledon aperture during seedling deetiolation. In darkness, ABA accumulates in the cotyledons to effectively repress their opening. However, light exposure reverses this effect, allowing the cotyledons to open. Our findings indicate that the ABA-mediated regulation of cotyledon dynamics is accompanied by genome-wide rearrangements in both transcriptional and splicing patterns. We demonstrate that the ABA-dependent adjustments of cotyledon and splicing dynamics in response to light depend on the positive role of two splicing factors, RS40 and RS41. Moreover, we identify transcriptional and posttranscriptional mechanisms that repress the activity of these proteins in the dark. Altogether, this work sheds light on the interplay between light and ABA, highlighting a new developmental outcome: cotyledon opening, and identifying a novel layer of gene regulation: alternative splicing.
Spatial transcriptomic analysis of HIV and tuberculosis coinfection in a humanized mouse model reveals specific transcription patterns, immune responses and early morphological alteration signaling
Authors: Adduri Sitaramaraju , Bohorquez Jose Alejandro , Adejare Omoyeni , Rincon Diego , Tucker Torry , Konduru Nagarjun V , Yi Guohua
Published: January 2025

Mycobacterium tuberculosis(Mtb) and human immunodeficiency virus (HIV) coinfection is one of the biggest public health concerns worldwide. Both pathogens are adept at modulating immune response and, in the case ofMtb, even inducing structural modification of the affected tissue. The present study aimed at understanding the early phenotypical and functional changes in immune cell infiltration in the affected organ, using a humanized mouse model. The humanized mice were infected with either HIV orMtbin single infection, or with both pathogens in coinfection. Three weeks after the infection, lung samples were collected, and spatial transcriptomics analysis was performed. This analysis revealed high infiltration of CD4+T cells inMtbinfection, but not in HIV or coinfection. Coinfected mice also showed a minimal number of NK cells compared to the other groups. In addition to infection status, histological features also influenced the immune cell infiltration pattern in the lungs. Two distinct airway regions with distinct immune cell abundance patterns were detected by spatial transcriptome profiling. A lymphoid cell aggregate detected in coinfection lung exhibited distinct transcript profile. The cellular architecture in the lymphoid cell aggregate did not follow the spatial patterns seen in mature granulomas. However, lymphoid cell aggregates exhibited granuloma gene expression signatures, and pathways associated with reactive oxygen species production, oxidative phosphorylation, and TGFβ and interferon signaling similar to granulomas. This study revealed specific transcription patterns, immune responses and morphological alteration signaling in the early stage of HIV andMtbinfections.
Single cell-resolved transcriptional dynamics of human subcutaneous adipose tissue during lifestyle- and bariatric surgery-induced weight loss
Authors: Loft Anne , Rydbirk Rasmus , Klinggaard Ellen Gammelmark , Van Hauwaert Elvira Laila , Wernberg Charlotte Wilhelmina , Møller Andreas Fønss , Dam Trine Vestergaard , Hassan Mohamed Nabil , Maniyadath Babukrishna , Nielsen Ronni , Krag Aleksander , Kalucka Joanna , Schmidt Søren Fisker , Lauridsen Mette Enok Munk , Madsen Jesper Grud Skat , Mandrup Susanne
Published: January 2025

During sustained weight gain, human white adipose tissue undergoes dramatic remodeling that may compromise adipose tissue function and lead to obesity comorbidities such as cardiometabolic disease. These comorbidities can be at least partially reversed by weight loss; however, the degree to which human adipose tissue is remodeled during weight loss is currently unclear. Here, we have used snRNA-seq combined with bulk RNA-seq and 3D light microscopy to investigate the cellular and transcriptional alterations in abdominal subcutaneous adipose tissue (ASAT) from a unique cohort of obese individuals undergoing initially modest (8-10%) lifestyle-induced weight loss followed by a more dramatic (20-45%) bariatric surgery-induced weight loss. We show that in response to this weight loss, ASAT in both males and females underwent dramatic compositional and transcriptional remodeling. Most notably, surgery-indued weight loss led to an increase in the adipose vascular compartment, a dramatic reduction in proinflammatory immune cells, and a tissue-wide reduction in inflammatory gene signatures. In response to modest weight loss, we observed an increase in specific progenitor populations and an induction of proadipogenic genes, indicating that this process is important for the early adaptation of AT to weight loss that might contribute to the early overall beneficial effects on insulin sensitivity and systemic inflammation.
Processivity and BDNF-dependent modulation of signalling endosome axonal transport are impaired in aged mice
Authors: Villarroel-Campos David , Rhymes Elena R. , Tosolini Andrew P. , Malik Bilal , Vagnoni Alessio , Schiavo Giampietro , Sleigh James N.
Published: January 2025

A healthy nervous system is reliant upon an efficient transport network to deliver essential cargoes throughout the extensive and polarised architecture of neurons. The trafficking of cargoes, such as organelles and proteins, is particularly challenging within the long projections of neurons, which, in the case of axons, can be more than four orders of magnitude longer than cell bodies. It is therefore unsurprising that disruptions in axonal transport have been reported across neurological diseases. A decline in this essential process has also been identified in many aging models, perhaps compounding age-related neurodegeneration. Via intravital imaging, we recently determined that, despite a reduction in overall motility, the run speed and displacement of anterograde mitochondrial transport were unexpectedly enhanced in aged mouse peripheral nerves. Here, to determine how aging impacts a different axonal cargo, we evaluatedin vivotrafficking of signalling endosomes in motor axons of mouse sciatic nerves from 3 to 22 months. Contrasting with mitochondria, we did not detect alterations in signalling endosome speed, but found a consistent rise in pausing that manifested after 18 months. We then treated muscles with brain-derived neurotrophic factor (BDNF), which regulates axonal transport of signalling endosomes in motor neurons; however, we observed no change in the processivity defect at 22 months, consistent with downregulation of the BDNF receptor TrkB at the neuromuscular junction. Together, these findings indicate that aging negatively impacts signalling endosome trafficking in motor axons likely through dampened BDNF signalling at the motor neuron-muscle interface.

Graphical Abstract
Immunity gene silencing increases transient protein expression inNicotiana benthamiana
Authors: Dodds Isobel L. , Watts Emma C. , Schuster Mariana , Buscaill Pierre , Tumtas Yasin , Holton Nicholas J. , Song Shijian , Stuttmann Johannes , Joosten Matthieu H. A. J. , Bozkurt Tolga O. , van der Hoorn Renier A. L.
Published: January 2025

Agroinfiltration ofNicotiana benthamianais routinely used for transient gene expression in plant sciences and molecular pharming. Here, we depleted transcripts of 21 different immunity-related genes through virus-induced gene silencing (VIGS) to identify genes that hamper transient expression in juvenile plants. These experiments uncovered that silencing ofethylene insensitive- 2(EIN2), receptor-like kinaseCERK1, transcription factor regulatornonexpressor of pathogenesis-related genes 1(NPR1) andisochorismate synthase(ICS), increases transient GFP expression by 2-, 4-, 4- and 11-fold, respectively. Accordingly, thenpr1a/npr1bdouble mutant ofN. benthamianadoes indeed facilitate increased protein accumulation when transiently expressed. These results indicate that glycan perception through CERK1, and ET and SA signaling pathways via EIN2 and NPR1/ICS, respectively, contribute to suppressed transient gene expression in frequently used juvenileN. benthamianaplants.
Multimodal synapse analysis reveals restricted integration of transplanted neurons remodeled by TREM2
Authors: Zarb Yvette , Thorwirth Manja , Markkula Oskar , Paoli Emanuele , Martinez-Reza Maria Fernanda , Todorov Mihail , Koupoutidou Christina , Schwarz Veronika , Kislinger Georg , Mezydlo Alexandra , Puglisi Matteo , Willem Michael , Ninkovic Jovica , Conzelmann Karl-Klaus , Schifferer Martina , Haass Christian , Kerschensteiner Martin , Portugues Ruben , Kopp-Scheinpflug Conny , Goetz Magdalena
Published: January 2025

Neural circuit responses arise from computations across diverse synapses within a neuron, making synaptic integration a crucial parameter to restore function after injury. Neuron transplantation offers a promising approach for circuit restoration after injury, but our knowledge of transplanted neuron (tN) synaptic connectivity remains limited. Here, we used a stab wound injury model, to examine how synapses of tNs mature and integrate using multimodal read-outs. We analyzed the morphological, ultrastructural and functional aspects of tN synapses and found surprising misalignments, such as many spines without synapses or many shaft synapses that are not inhibitory, pointing towards immature aspects even 3 months post transplantation. Spatial transcriptomics revealed persistent inflammatory signatures at the transplant site including Trem2 upregulation. Indeed, the excessive pruning of the brain-wide input connectome of tNs was much improved in an environment devoid of TREM2, highlighting the importance of tackling the chronic inflammation for adequate tN integration.
Novel Laser Technology Enables 10x Faster SRS Imaging and Rapid Tuning in Biological Samples
Authors: Reinkensmeier Lenny , Siegmund René , Bates Mark , Stibenz Gero , Trabs Peter , Popien Stefan , Rimke Ingo , Heuke Sandro , Egner Alexander
Published: January 2025

Stimulated Raman Scattering (SRS) microscopy was developed for the label-free detection of molecular groups, addressing the speed limitations of spontaneous Raman microscopy. Standard SRS microscopy typically operates with laser sources at an 80 MHz repetition rate and a color-tuning speed of approximately 0.1 Hz to target different molecular groups. Here, we present a novel laser system that overcomes these speed limitations, achieving an order-of-magnitude improvement in both color-tuning and imaging speed. Our system features a reduced repetition rate of 40 MHz, enabling SRS imaging that is ten times faster than standard systems while maintaining the same average power at the sample. This is achieved through increased pulse energy and laser modulation at half the repetition rate. Furthermore, the system provides nearly ten times faster color-tuning across an extended range (660–1010 nm) by employing angle-tuning of nonlinear crystals instead of temperature-tuning. The improved performance is demonstrated in direct comparison with a standard SRS laser system, showcasing the potential for significantly enhanced imaging capabilities.
Exploring the sequential structure of students’ physics problem-solving approaches using process mining and sequence analysis
Authors: Tschisgale Paul , Kubsch Marcus , Wulff Peter , Petersen Stefan , Neumann Knut
Published: January 2025

Problem solving is considered an essential ability for becoming an expert in physics, and individualized feedback on the structure of problem-solving processes is a key component to support students in developing this ability. Problem-solving processes consist of multiple elements whose order forms the sequential structure of these processes. Specific sequential structures can be expected to better reflect expert problem solving and more likely lead to successful solutions. However, this sequential structure often receives limited attention in assessments, thereby neglecting possibly valuable diagnostic information that could be used for individualized feedback. Consequently, a deeper understanding of the sequential structure of students’ written physics problem-solving approaches could leverage novel potentials for physics instruction and feedback provision. This study therefore aimed to examine how the sequential structure of written problem-solving approaches differs between high- and low-performing problem solvers as well as to what extent specific sequential elements are predictive of problem-solving performance. To achieve this, we employed methods from process mining and sequence analysis research. Our findings revealed that low-performing problem solvers often lack structure in their problem-solving approaches, contrasting with notably more systematic approaches of the high-performing problem solvers. Additionally, the order in which assumptions and conceptual aspects are addressed in a problem-solving approach seems to be an indicator of problem-solving performance. The findings of this study enhance our understanding of physics problem-solving processes and highlight opportunities for improving instruction and feedback for physics problem solving by considering the sequential structure of students’ physics problem-solving approaches.

Published by the American Physical Society
2025
Unit-cell parameters determination from a set of independent electron diffraction zonal patterns
Authors: Gorelik Tatiana E. , Miehe Gerhard , Bücker Robert , Yoshida Kaname
Published: January 2025

Due to the short de Broglie wavelength of electrons compared with X-rays, the curvature of their Ewald sphere is low, and individual electron diffraction patterns are nearly flat in reciprocal space. As a result, a reliable unit-cell determination from a set of randomly oriented electron diffraction patterns, an essential step in serial electron diffraction, becomes a non-trivial task. Here we describe an algorithm for unit-cell determination from a set of independent electron diffraction patterns, as implemented in the program PIEP (Program for Interpreting Electron diffraction Patterns), written in the early 1990s. We evaluate the performance of the algorithm by unit-cell determination of two known structures – copper perchlorophthalocyanine (CuPcCl16) and lysozyme, challenging the algorithm by high-index zone patterns and long crystallographic axes. Finally, we apply the procedure to a new, structurally uncharacterized five amino acid peptide.
Safer facility floor designing: a tribological insight into optimising ceramic tile surface textures for enhanced slip resistance
Authors: Kim In-Ju
Published: January 2025

Purpose

This study aims to enhance pedestrian safety by investigating the slip resistance of facility floors with ceramic tile surfaces and identifying critical surface roughness parameters that influence slip resistance.

Design/methodology/approach

Dynamic friction tests and comprehensive surface roughness analyses were conducted on ceramic tiles. Statistical analysis identified optimal roughness ranges for key parameters (Ra, Rp, Rt, Rz and Rv) to ensure the dynamic friction coefficient exceeds 0.5 to meet safety requirements. This study assessed different textures under dry, damp and foamy conditions.

Findings

The findings reveal that ceramic tile surfaces with higher peak heights and deeper valleys provide superior traction, particularly in damp and foamy conditions. The results demonstrate that specific surface textures can effectively mitigate slip and fall hazards by enhancing grip and increasing surface interaction points. This study establishes optimal roughness ranges for the critical parameters, providing a robust framework for improving slip resistance.

Originality/value

This study offers practical guidelines for designing safer ceramic tiles, emphasising the importance of tailored surface roughness to improve traction. It highlights the importance of considering environmental factors in slip resistance assessments, offering valuable insights for manufacturers, designers and policymakers. By focusing on specific surface textures, this study advances the development of safer built environments in public facilities. Future research directions should explore a broader range of tile finishes, footwear types and contaminant scenarios to refine the understanding of traction performance further.
Comparative transcriptomics and metabolomics provide insight into degeneration‐related physiological mechanisms of Morchella importuna after long‐term preservation
Authors: Chen Ying , Cao Xuelian , Xie Liyuan , Tang Jie , Liu Lixu , Wang Di , Wu Xiang , Liu Tianhai , Yu Yang , Wang Yong , Martin Francis , Peng Weihong , Tan Hao
Published: January 2025

Ascomycetes fungi are often prone to degeneration. Agricultural production of the prized ascomycete mushroom Morchella importuna (black morel) typically suffers from reduced yield and malformed ascocarps owing to culture degeneration. This study compared M. importuna cultures subjected to five different long‐term preservation treatments, using transcriptomics and metabolomics. Avoiding repeated subculturing in combination with nutrient‐limited conditions was found to be the most beneficial method for maintaining the fruiting capability of morels. The expression of the gene sets involved in cysteine and methionine metabolism and nucleocytoplasmic transport was upregulated under nutrient‐limited and nutrient‐rich conditions, respectively. This increased expression was accompanied by differential accumulation of metabolites involved in nucleobase metabolism. Repeated subculturing triggered dissimilar changes in the functional modules under nutrient‐rich and nutrient‐limited conditions. A diverse set of cellular biochemical processes related to carbon metabolism were altered by repeated subculturing under nutrient‐rich conditions, whereas glycerophospholipid and purine metabolism were key functions affected by repeated subculturing under nutrient‐limited conditions. Altogether, metabolic alterations related to sulfur‐containing amino‐acid biosynthesis, DNA repair, and cellular structural maintenance contributed to improved preservation outcomes in terms of morel fruiting capability. Our findings contribute to a more detailed understanding of the molecular mechanisms related to subculturing and fruiting of ascomycete macrofungi after long‐term preservation.
Uruguayan Grasslands: A Threatened Natural Asset
Authors: Guido Anaclara , López‐Mársico Luis , Rodríguez Claudia , Gallego Federico , Lezama Felipe , Baeza Santiago , Pañella Pedro , Ríos Cecilia , Costa Beatriz , Pezzani Fabiana , García Silvina , Piñeiro Gervasio , Fernández Gastón , Tommasino Andrea , Mello Ana Laura , Altesor Alice , Paruelo José
Published: January 2025

Grasslands are often mis‐defined, mainly due to the legacy of colonial narratives in several regions, which have described them as deforested, unproductive or wastelands. They have been largely ignored in global conservation and protection policies, leading to increased exploitation. Although there is much accumulated evidence on the ecosystem services that grasslands provide, in Uruguay, this ecosystem is still neglected in parts of society and for most sustainability policies. Twenty percent of Uruguayan grasslands have been replaced by other land uses (crops and forestry) in recent decades. Nevertheless, large areas of natural grasslands still remain and their preservation is crucial. The aim of this work was to show the value of Uruguayan grasslands through a brief review of their natural history and their multiple natural assets (i.e., biodiversity, ecosystem services, cultural identity and economic activities). We also outline some of the advances in public policy initiatives, but emphasise that such policies are critically underdeveloped in terms of conservation, threatening the existence of grasslands in Uruguay for future generations.
Glycopyrronium 320 μg/mL in children and adolescents with severe sialorrhoea and neurodisabilities: An open‐label study extension of the SALIVA trial
Authors: Fayoux Pierre , Dinomais Mickael , Shaw Helen , Villain Frédéric , Schwartz Déborah , Gautheron Vincent , Letellier Guy , Auvin Stéphane
Published: January 2025

Aims

To test the long‐term efficacy, safety, and impact on quality of life (QoL) of an oral paediatric formulation of 320 μg/mL glycopyrronium in the 36‐week SALIVA (Sialanar plus orAl rehabiLitation against placebo plus oral rehabilitation for chIldren and adolescents with seVere sialorrhoeA and neurodisabilities) trial.

Method

In the initial 12‐week blinded period, 87 children with neurodisabilities and severe sialorrhoea were randomized to 320 μg/mL glycopyrronium versus placebo. In the subsequent 24‐week open‐label study extension, 74 children received 320 μg/mL glycopyrronium (37 continued glycopyrronium, 37 switched from placebo).

Results

The open‐label study extension population included 39 males and 35 females. The median age was 10 years 2 months (quartile 1, quartile 3: 7 years 5 months, 14 years 7 months; range: 3 years 5 months–17 years 8 months). Over 36 weeks, continued 320 μg/mL glycopyrronium resulted in a median 39‐point reduction in Drooling Impact Scale (DIS) score from baseline (quartile 1, quartile 3: −51, −21; p < 0.001), with an 81.1% response rate (DIS improvement ≥ 13.6 points) and a 70.3% good response rate (≥ 28 points). Improvements in the impact of drooling on QoL seen in the blinded period were sustained with continued glycopyrronium. Treatment‐related adverse events occurred most frequently during titration (0–4 weeks: 40.9%; 5–20 weeks: 32.4% in those who switched). Constipation was the most common adverse event.

Interpretation

Long‐term treatment with 320 μg/mL glycopyrronium resulted in significant sustained improvements in drooling and QoL, with fewer adverse events after initial titration and overall good tolerability.