bluuebunny/crossref_metadata_2025 huggingface dataset:
Declining cost of renewables and climate change curb the need for African hydropower expansion
Authors: Carlino Angelo , Wildemeersch Matthias , Chawanda Celray James , Giuliani Matteo , Sterl Sebastian , Thiery Wim , van Griensven Ann , Castelletti Andrea
Published: August 2023

Across continental Africa, more than 300 new hydropower projects are under consideration to meet the future energy demand that is expected based on the growing population and increasing energy access. Yet large uncertainties associated with hydroclimatic and socioeconomic changes challenge hydropower planning. In this work, we show that only 40 to 68% of the candidate hydropower capacity in Africa is economically attractive. By analyzing the African energy systems’ development from 2020 to 2050 for different scenarios of energy demand, land-use change, and climate impacts on water availability, we find that wind and solar outcompete hydropower by 2030. An additional 1.8 to 4% increase in annual continental investment ensures reliability against future hydroclimatic variability. However, cooperation between countries is needed to overcome the divergent spatial distribution of investment costs and potential energy deficits.
Loss of terrestrial biodiversity in Australia: Magnitude, causation, and response
Authors: Legge Sarah , Rumpff Libby , Garnett Stephen T. , Woinarski John C. Z.
Published: August 2023

Australia’s biota is species rich, with high rates of endemism. This natural legacy has rapidly diminished since European colonization. The impacts of invasive species, habitat loss, altered fire regimes, and changed water flows are now compounded by climate change, particularly through extreme drought, heat, wildfire, and flooding. Extinction rates, already far exceeding the global average for mammals, are predicted to escalate across all taxa, and ecosystems are collapsing. These losses are symptomatic of shortcomings in resourcing, law, policy, and management. Informed by examples of advances in conservation practice from invasive species control, Indigenous land management, and citizen science, we describe interventions needed to enhance future resilience. Many characteristics of Australian biodiversity loss are globally relevant, with recovery requiring society to reframe its relationship with the environment.
Chemical upcycling of polyethylene, polypropylene, and mixtures to high-value surfactants
Authors: Xu Zhen , Munyaneza Nuwayo Eric , Zhang Qikun , Sun Mengqi , Posada Carlos , Venturo Paul , Rorrer Nicholas A. , Miscall Joel , Sumpter Bobby G. , Liu Guoliang
Published: August 2023

Conversion of plastic wastes to fatty acids is an attractive means to supplement the sourcing of these high-value, high-volume chemicals. We report a method for transforming polyethylene (PE) and polypropylene (PP) at ~80% conversion to fatty acids with number-average molar masses of up to ~700 and 670 daltons, respectively. The process is applicable to municipal PE and PP wastes and their mixtures. Temperature-gradient thermolysis is the key to controllably degrading PE and PP into waxes and inhibiting the production of small molecules. The waxes are upcycled to fatty acids by oxidation over manganese stearate and subsequent processing. PP ꞵ-scission produces more olefin wax and yields higher acid-number fatty acids than does PE ꞵ-scission. We further convert the fatty acids to high-value, large–market-volume surfactants. Industrial-scale technoeconomic analysis suggests economic viability without the need for subsidies.
Hydroformylation of pyrolysis oils to aldehydes and alcohols from polyolefin waste
Authors: Li Houqian , Wu Jiayang , Jiang Zhen , Ma Jiaze , Zavala Victor M. , Landis Clark R. , Mavrikakis Manos , Huber George W.
Published: August 2023

Waste plastics are an abundant feedstock for the production of renewable chemicals. Pyrolysis of waste plastics produces pyrolysis oils with high concentrations of olefins (>50 weight %). The traditional petrochemical industry uses several energy-intensive steps to produce olefins from fossil feedstocks such as naphtha, natural gas, and crude oil. In this work, we demonstrate that pyrolysis oil can be used to produce aldehydes through hydroformylation, taking advantage of the olefin functionality. These aldehydes can then be reduced to mono- and dialcohols, oxidized to mono- and dicarboxylic acids, or aminated to mono- and diamines by using homogeneous and heterogeneous catalysis. This route produces high-value oxygenated chemicals from low-value postconsumer recycled polyethylene. We project that the chemicals produced by this route could lower greenhouse gas emissions ~60% compared with their production through petroleum feedstocks.
Justice, culture, and relationships: Australian Indigenous prescription for planetary health
Authors: Matthews Veronica , Vine Kristina , Atkinson Amba-Rose , Longman Jo , Lee Grace W. , Vardoulakis Sotiris , Mohamed Janine
Published: August 2023

Indigenous communities shoulder a disproportionate burden of ill health compounded by climate change. In Australia, the oldest surviving cultures have adapted their ecological knowledge over millennia and across climatic ages. However, European colonization has severely curtailed Indigenous peoples’ ability to adjust to climate change. An effective response to the climate crisis requires decolonizing processes to reform our relationship with the planet. From an Australian Indigenous perspective, precursors for a self-determined and healthier future are justice, culture, and relationships. We review existing studies on Indigenous-led contemporary climate and health initiatives to assess these precursors. There are examples that highlight the need to attend to issues of restorative justice as the basis for respectful valuing of culture and genuine collaboration to address the climate crisis.
Cell polarity linked to gravity sensing is generated by LZY translocation from statoliths to the plasma membrane
Authors: Nishimura Takeshi , Mori Shogo , Shikata Hiromasa , Nakamura Moritaka , Hashiguchi Yasuko , Abe Yoshinori , Hagihara Takuma , Yoshikawa Hiroshi Y. , Toyota Masatsugu , Higaki Takumi , Morita Miyo Terao
Published: August 2023

Organisms have evolved under gravitational force, and many sense the direction of gravity by means of statoliths in specialized cells. In flowering plants, starch-accumulating plastids, known as amyloplasts, act as statoliths to facilitate downstream gravitropism. The gravity-sensing mechanism has long been considered a mechanosensing process by which amyloplasts transmit forces to intracellular structures, but the molecular mechanism underlying this has not been elucidated. We show here that LAZY1-LIKE (LZY) family proteins involved in statocyte gravity signaling associate with amyloplasts and the proximal plasma membrane. This results in polar localization according to the direction of gravity. We propose a gravity-sensing mechanism by which LZY translocation to the plasma membrane signals the direction of gravity by transmitting information on the position of amyloplasts.
Linnaeus and his life’s work
The Man Who Organized Nature: The Life of Linnaeus
Gunnar Broberg, Translated by Anna Paterson
Princeton University Press, 2023. 512 pp.
Authors: Incorvaia Darren
Published: August 2023

A historian’s unvarnished biography reveals the complicated man who invented modern taxonomy
Tissue adhesive semiconductors
Authors: Wu Sarah J. , Zhao Xuanhe
Published: August 2023

Bioelectronic implants could use semiconductors that adhere to wet, dynamic tissues
A mammalian DNA methylation landscape
Authors: de Mendoza Alex
Published: August 2023

A study of 348 species offers clues into the diversity of mammalian life spans
We need a Weizenbaum test for AI
Authors: Stilgoe Jack
Published: August 2023

Alan Turing introduced his 1950 paper on Computing Machinery and Intelligence with the question
“Can machines think?”
But rather than engaging in what he regarded as never-ending subjective debate about definitions of intelligence, he instead proposed a thought experiment. His “imitation game” offered a test in which an evaluator held conversations with a human and a computer. If the evaluator failed to tell them apart, the computer could be said to have exhibited artificial intelligence (AI).

In the decades since Turing’s paper, AI has gone from being a fountain of scientific hype to an academic backwater to a gold rush. Throughout, the Turing test has given computer scientists a sense of direction: a quest for what Turing called a “universal machine.” Although the debate continues about whether the Turing test is a reasonable measure of artificial intelligence, the real problem is that it asks the wrong question. AI is no longer an academic debate. It is a technological reality. For society to make good decisions about AI, we should instead look to another great late 20th-century computer scientist, Joseph Weizenbaum. In a paper

“On the impact of the computer on society,” in
Science
in 1972

, Weizenbaum argued that his fellow computer scientists should try to view their activities from the standpoint of a member of the public. Whereas computer scientists wonder how to get their technology to work and use “electronic wizardry” to make it safe, Weizenbaum argued that ordinary people would ask “is it good?” and “do we need these things?” As excitement builds about the possibilities of generative AI, rather than asking whether these machines are intelligent, we should instead ask whether they are useful.
Deep spatial profiling of Venezuelan equine encephalitis virus reveals increased genetic diversity amidst neuroinflammation and cell death during brain infection
Authors: Williams Evan P. , Xue Yi , Lee Jasper , Fitzpatrick Elizabeth A. , Kong Ying , Reichard Walter , Writt Haley , Jonsson Colleen B.
Published: August 2023

Venezuelan equine encephalitis virus (VEEV) causes a febrile illness that can progress to neurological disease with the possibility of death in human cases. The evaluation and optimization of therapeutics that target brain infections demands knowledge of the host’s response to VEEV, the dynamics of infection, and the potential for within-host evolution of the virus. We hypothesized that selective pressures during infection of the brain may differ temporally and spatially and so we investigated the dynamics of the host response, viral transcript levels, and genetic variation of VEEV TC-83 in eight areas of the brain in mice over 7 days post-infection (dpi). Viral replication increased throughout the brain until 5–6 dpi and decreased thereafter with neurons as the main site of viral replication. Low levels of genetic diversity were noted on 1 dpi and were followed by an expansion in the genetic diversity of VEEV and nonsynonymous (Ns) mutations that peaked by 5 dpi. The pro-inflammatory response and the influx of immune cells mirrored the levels of virus and correlated with substantial damage to neurons by 5 dpi and increased activation of microglial cells and astrocytes. The prevalence and dynamics of Ns mutations suggest that the VEEV is under selection within the brain and that progressive neuroinflammation may play a role in acting as a selective pressure.

IMPORTANCE

Treatment of encephalitis in humans caused by Venezuelan equine encephalitis virus (VEEV) from natural or aerosol exposure is not available, and hence, there is a great interest to address this gap. In contrast to natural infections, therapeutic treatment of infections from aerosol exposure will require fast-acting drugs that rapidly penetrate the blood-brain barrier, engage sites of infection in the brain and mitigate the emergence of drug resistance. Therefore, it is important to understand not only VEEV pathogenesis, but the trafficking of the viral population within the brain, the potential for within-host evolution of the virus, and how VEEV might evolve resistance.
Construction and Modification of Debris-Flow Alluvial Fans as Captured in the Geomorphic and Sedimentary Record: Examples from the Western Sangre de Cristo Mountains, South-Central Colorado
Authors: Nicovich* Sylvia R. , Schmitt James G. , Gray Harrison J. , Klinger Ralph E. , Mahan Shannon A.
Published: August 2023

Debris-flow alluvial fans are iconic features of dynamic landscapes and are hypothesized to record tectonic and climatic change. Here, we highlight their complex formation and evolution through an exemplary suite of Quaternary debris-flow alluvial fans emanating from the western range front of the Sangre de Cristo Mountains in south-central Colorado, USA. To evaluate the constructive and modifying processes that produce fan form and the associated sedimentary signatures, we applied a combined geomorphologic and sedimentologic approach using sedimentary facies analysis, soils mapping, high-resolution topographic data, and luminescence geochronology to document timing of fan construction and modification. We explored two subsets of fans in the study area: a southern set sourced from the extensively glaciated drainages of the Blanca Peak massif, and a northern set from the unglaciated drainages south of Great Sand Dunes National Park. Both sets of fans have: (1) active and successively abandoned surfaces that show evolving degradation of primary features through modification by secondary processes, (2) associated facies that display distinct characteristics representative of primary depositional and secondary modifying sedimentary processes, and (3) evidence of primary debris flow with subsequent modification by secondary processes. We found that surface geomorphology and facies assemblages in exposed alluvial-fan deposits represent sediment transport processes on both active and abandoned lobes. The link between fan surface morphologies and the sedimentary facies of their deposits provides a basis for an evolutionary process–based interpretation of debris-flow alluvial-fan geomorphology and provides a better understanding of complexities in buried paleosurfaces (intraformational progressive unconformities), surficial deformation, and landform development as recorded in debris-flow fan deposits in the sedimentary record.
Presentation of multiple painful subcutaneous nodules: Dercum’s disease, a rare variant of lipoma
Authors: Hollands Maddison , Wee Cleo , Breidahl William , Xu Dan
Published: August 2023

A woman in her 50s presented to her general practitioner (GP) with an 8-month history of multiple painful subcutaneous nodules of various sizes in her trunk and limbs. Her previous GP made the clinical diagnosis of lipoma when they presented as non-painful nodules 2 years ago. Initial ultrasound demonstrated multiple lipomata with the largest size in the left upper thighs displaying features of subtle internal vascularity, entirely contained within the subcutaneous layer. MRI scan of thigh lesions showed multiple angiolipomas consistent with the entity of Dercum’s disease. Subsequent biopsy histology confirmed the image diagnosis of angiolipoma. She was referred to a musculoskeletal oncological surgeon for evaluation and reassurance regarding optimising medical management of her associated obesity. Her angiolipoma and obesity are well managed by her GP. This case highlights the diagnostic workup of a rare variant of lipoma, Dercum’s disease. The differential diagnosis of multiple painful lipomas was reviewed and discussed, consequently leading to the discussion of managing the associated obesity in this case.
Predictive performance of the STarT Back tool for poor outcomes in patients with low back pain: protocol for a systematic review and meta-analysis
Authors: Fang Yunhua , Chen Jie , Lin Shengmei , Cai Yangfan , Huang Lian-Hong
Published: August 2023

Introduction

Subgroups for Targeted Treatment Back Tool (SBT) is a brief multiple-construct risk prediction tool for patients with low back pain (LBP). Thus far, the predictive ability of this tool has been inconsistent. Therefore, we aim to conduct a literature review on the predictive ability of the SBT to determine the outcomes of patients with LBP. The results of this review should improve the ability of the SBT to predict poor outcomes in patients with LBP.

Methods and analysis

Databases including PubMed, EMBASE, Cochrane Central, Web of Science, Chinese National Knowledge Infrastructure Databases, Chinese Science and Technology Journal Database, and Wanfang will be searched for studies on SBT and LBP from their inception until 31 March 2023. Longitudinal studies investigating the association between SBT subgroups and LBP outcomes, including pain, disability and quality of life, will be included. The identified studies will be independently screened for eligibility by two reviewers. A standardised sheet will be used to extract data. The Newcastle-Ottawa Scale will be used to assess the methodological quality of the included studies. Heterogeneity will be evaluated by the χ2test with Cochran’s Q statistic and quantified by the I2statistic. The results will be synthesised qualitatively and presented as pooled risk ratios or beta coefficients quantitatively. The results will also be presented using their 95% confidence limits. Publication bias will be assessed using the method proposed by Egger and by visual inspection of funnel plots.

Ethics and dissemination

This study is a secondary analysis of original studies that received ethics approval. Therefore, prior ethical approval is not required for this study. The findings will be submitted to relevant peer-reviewed journals for publication and presented at profession-specific conferences.

Trial registration number

PROSPERO registration number

CRD42022309189.
Recruiting and retaining bachelor qualified nurses in German hospitals (BSN4Hospital): protocol of a mixed-methods design
Authors: Maier Claudia B , Köppen Julia , Kleine Joan , McHugh Matthew D , Sermeus Walter , Aiken Linda H
Published: August 2023

Introduction

Many countries in Europe are facing a shortage of nurses and seek effective recruitment and retention strategies. The nursing workforce is increasingly diverse in its educational background, ranging from 3-year vocational training (diploma) to bachelor and master educated nurses. This study analyses recruitment and retention strategies for academically educated nurses (minimum bachelor), including intention to leave, job satisfaction and work engagement compared with diploma nurses in innovative German hospitals; it explores recruitment and retention challenges and opportunities, and identifies lessons on recruitment and retention taking an international perspective.

Methods and analysis

The study will apply a convergent mixed-methods design, including qualitative and quantitative methods. The qualitative study will include semistructured interviews among hospital managers, nurses, students and stakeholders in Germany. In addition, expert interviews will be conducted internationally in countries with a higher proportion of bachelor/master nurses in hospitals. The quantitative, cross-sectional study will consist of a survey among professional nurses (bachelor/master, diploma nurses) in German hospitals. Study settings are hospitals with a higher-than-average proportion of bachelor nurses or relevant recruitment, work environment or retention strategies in place. Analyses will be conducted in several phases, first in parallel, then combined via triangulation: the parallel analysis technique will analyse the qualitative and quantitative data separately via content analyses (interviews) and descriptive, bivariate and multivariate analyses (survey). Subsequently, data sources will be collectively analysed via a triangulation matrix focusing on developing thematic exploratory clusters at three systemic levels: microlevel, mesolevel and macrolevel. The analyses will be relevant for generating lessons for clinical nursing, management and policy in Germany and internationally.

Ethics and dissemination

Ethics approval was obtained by the Charité Ethics Committee.

Several dissemination channels will be used, including publications and presentations, for the scientific community, nursing management, clinical nurses and the wider public in Germany and internationally.
Improving survival in alcohol-related hepatitis: what's new?
Authors: Shearer Jessica , Johnson Amy , Masson Steven
Published: August 2023

Alcohol-related hepatitis (AH) is the most florid presentation of alcohol-related liver disease and carries a high short-term and long-term mortality rate. Specific treatment options remain inadequate. The current management approach for AH focuses on early identification, careful screening and treatment of infection, as well as identification of those patients who may benefit from corticosteroid therapy based on validated prognostic scoring systems.

In recent years, there has been growing interest in exploring novel therapies for AH, which may offer alternative treatment options beyond the traditional approaches. Additionally, early liver transplantation (LT) has emerged as a promising option in selected cases with growing evidence supporting its role. In this review, we will discuss the current evidence base for the assessment and treatment of AH, and how these advances are shaping practice to improve outcomes in the UK.
Disease-modifying interactions between chronic kidney disease and osteoarthritis: a new comorbid mouse model
Authors: Julovi Sohel M , Dao Aiken , Trinh Katie , O’Donohue Alexandra K , Shu Cindy , Smith Susan , Shingde Meena , Schindeler Aaron , Rogers Natasha M , Little Christopher B
Published: August 2023

Objective

The prevalence of comorbid chronic kidney disease (CKD) and osteoarthritis (OA) is increasing globally. While sharing common risk factors, the mechanism and consequences of concurrent CKD-OA are unclear. The aims of the study were to develop a preclinical comorbid model, and to investigate the disease-modifying interactions.

Methods

Seventy (70) male 8–10 week-old C57BL/6 mice were subjected to 5/6 nephrectomy (5/6Nx)±destabilisation of medial meniscus (DMM) or sham surgery. OA pathology and CKD were assessed 12 weeks postinduction by blinded histology scoring, micro-CT, immunohistochemistry for osteoclast and matrix metalloproteinase (MMP)-13 activity, and serum analysis of bone metabolic markers.

Results

The 5/6Nx model recapitulated characteristic features of CKD, with renal fibrosis and deranged serum alkaline phosphatase, calcium and phosphate. There was no histological evidence of cartilage pathology induced by 5/6Nx alone, however, synovial MMP-13 expression and subchondral bone osteoclastic activity were increased (p<0.05), with accompanying reductions (p<0.05) in subchondral trabecular bone, bone volume and mineral density. DMM significantly (p<0.05) increased tibiofemoral cartilage damage, subchondral bone sclerosis, marginal osteophytes and synovitis, in association with increased cartilage and synovial MMP-13. DMM alone induced (p<0.05) renal fibrosis, proteinuria and increased (p<0.05) 5/6Nx-induced serum urea. However, DMM in 5/6Nx-mice resulted in significantly reduced (p<0.05) cartilage pathology and marginal osteophyte development, in association with reduced subchondral bone volume and density, and inhibition of 5/6Nx-induced subchondral bone osteoclast activation.

Conclusion

This study assessed a world-first preclinical comorbid CKD-OA model. Our findings demonstrate significant bidirectional disease-modifying interaction between CKD and OA.
Pair production of the open superstrings from the parallel-dressed D3-branes in the compact spacetime
Authors: Barghi-Janyar Niloufar , Kamani Davoud
Published: August 2023

We employ the boundary state formalism to compute the pair creation rate of the open superstrings from the interaction of two parallel D3-branes. The branes live in the partially compact spacetime. In addition, they have been dressed with the internal gauge potentials and the Kalb–Ramond field.
Self-force effects around charged (2+1)-dimensional BTZ black hole in the Einstein–Gauss–Bonnet gravity
Authors: Ahmed Ayyesha K. , Siddiqui Azad A.
Published: August 2023

In this paper, we discuss a mode sum regularization method for the self-force acting on a charged test particle moving around a Banados, Teitelboim and Zanelli (BTZ) black hole. First, we have calculated the self-force on each individual mode. Then we evaluated our result by summing up the contribution on each mode. We studied a general scheme for static black holes and then present the result for radial trajectories around [Formula: see text]-dimensional charged BTZ black hole in Einstein–Gauss–Bonnet (EGB) gravity. We find that the parameter which is coupling ([Formula: see text]) GR to Einstein–Gauss–Bonnet gravity has a significant impact on the self-force.
Trusting My Predictions: On the Value of Instance-Level Analysis
Authors: Lorena Ana C. , Paiva Pedro Y. A. , Prudêncio Ricardo B. C.
Published: August 2023

Machine Learning solutions have spread along many domains, including critical applications. The development of such models usually relies on a dataset containing labeled data. This dataset is then split into training and test sets and the accuracy of the models in replicating the test labels is assessed. This process is often iterated in a cross-validation procedure for obtaining average performance estimates. But is the average of the predictive performance on test sets enough for assessing the trustfulness of a Machine Learning model? This paper discusses the importance of knowing which individual observations of a dataset are more challenging than others and how this characteristic can be measured and used in order to improve classification performance and trustfulness. A set of strategies for measuring the hardness level of the instances of a dataset is surveyed and a Python package containing their implementation is provided.
Identification of Splice Variants and Isoforms in Transcriptomics and Proteomics
Authors: Su Taojunfeng , Hollas Michael A.R. , Fellers Ryan T. , Kelleher Neil L.
Published: August 2023

Alternative splicing is pivotal to the regulation of gene expression and protein diversity in eukaryotic cells. The detection of alternative splicing events requires specific omics technologies. Although short-read RNA sequencing has successfully supported a plethora of investigations on alternative splicing, the emerging technologies of long-read RNA sequencing and top-down mass spectrometry open new opportunities to identify alternative splicing and protein isoforms with less ambiguity. Here, we summarize improvements in short-read RNA sequencing for alternative splicing analysis, including percent splicing index estimation and differential analysis. We also review the computational methods used in top-down proteomics analysis regarding proteoform identification, including the construction of databases of protein isoforms and statistical analyses of search results. While many improvements in sequencing and computational methods will result from emerging technologies, there should be future endeavors to increase the effectiveness, integration, and proteome coverage of alternative splicing events.
The All of Us Data and Research Center: Creating a Secure, Scalable, and Sustainable Ecosystem for Biomedical Research
Authors: Mayo Kelsey R. , Basford Melissa A. , Carroll Robert J. , Dillon Moira , Fullen Heather , Leung Jesse , Master Hiral , Rura Shimon , Sulieman Lina , Kennedy Nan , Banks Eric , Bernick David , Gauchan Asmita , Lichtenstein Lee , Mapes Brandy M. , Marginean Kayla , Nyemba Steve L. , Ramirez Andrea , Rotundo Charissa , Wolfe Keri , Xia Weiyi , Azuine Romuladus E. , Cronin Robert M. , Denny Joshua C. , Kho Abel , Lunt Christopher , Malin Bradley , Natarajan Karthik , Wilkins Consuelo H. , Xu Hua , Hripcsak George , Roden Dan M. , Philippakis Anthony A. , Glazer David , Harris Paul A.
Published: August 2023

The All of Us Research Program's Data and Research Center (DRC) was established to help acquire, curate, and provide access to one of the world's largest and most diverse datasets for precision medicine research. Already, over 500,000 participants are enrolled in All of Us, 80% of whom are underrepresented in biomedical research, and data are being analyzed by a community of over 2,300 researchers. The DRC created this thriving data ecosystem by collaborating with engaged participants, innovative program partners, and empowered researchers. In this review, we first describe how the DRC is organized to meet the needs of this broad group of stakeholders. We then outline guiding principles, common challenges, and innovative approaches used to build the All of Us data ecosystem. Finally, we share lessons learned to help others navigate important decisions and trade-offs in building a modern biomedical data platform.
Host Plant Effects on Sexual Selection Dynamics in Phytophagous Insects
Authors: Jarrett Benjamin J.M. , Miller Christine W.
Published: August 2023

Natural selection is notoriously dynamic in nature, and so, too, is sexual selection. The interactions between phytophagous insects and their host plants have provided valuable insights into the many ways in which ecological factors can influence sexual selection. In this review, we highlight recent discoveries and provide guidance for future work in this area. Importantly, host plants can affect both the agents of sexual selection (e.g., mate choice and male–male competition) and the traits under selection (e.g., ornaments and weapons). Furthermore, in our rapidly changing world, insects now routinely encounter new potential host plants. The process of adaptation to a new host may be hindered or accelerated by sexual selection, and the unexplored evolutionary trajectories that emerge from these dynamics are relevant to pest management and insect conservation strategies. Examining the effects of host plants on sexual selection has the potential to advance our fundamental understanding of sexual conflict, host range evolution, and speciation, with relevance across taxa.
How to Build a Fire: The Genetics of Autoinflammatory Diseases
Authors: Zhang Jiahui , Lee Pui Y. , Aksentijevich Ivona , Zhou Qing
Published: August 2023

Systemic autoinflammatory diseases (SAIDs) are a heterogeneous group of disorders caused by excess activation of the innate immune system in an antigen-independent manner. Starting with the discovery of the causal gene for familial Mediterranean fever, more than 50 monogenic SAIDs have been described. These discoveries, paired with advances in immunology and genomics, have allowed our understanding of these diseases to improve drastically in the last decade. The genetic causes of SAIDs are complex and include both germline and somatic pathogenic variants that affect various inflammatory signaling pathways. We provide an overview of the acquired SAIDs from a genetic perspective and summarize the clinical phenotypes and mechanism(s) of inflammation, aiming to provide a comprehensive understanding of the pathogenesis of autoinflammatory diseases.
Finding Needles in the Haystack: Strategies for Uncovering Noncoding Regulatory Variants
Authors: Chen You , Paramo Mauricio I. , Zhang Yingying , Yao Li , Shah Sagar R. , Jin Yiyang , Zhang Junke , Pan Xiuqi , Yu Haiyuan
Published: August 2023

Despite accumulating evidence implicating noncoding variants in human diseases, unraveling their functionality remains a significant challenge. Systematic annotations of the regulatory landscape and the growth of sequence variant data sets have fueled the development of tools and methods to identify causal noncoding variants and evaluate their regulatory effects. Here, we review the latest advances in the field and discuss potential future research avenues to gain a more in-depth understanding of noncoding regulatory variants.
Pooled Genome-Scale CRISPR Screens in Single Cells
Authors: Schraivogel Daniel , Steinmetz Lars M. , Parts Leopold
Published: August 2023

Assigning functions to genes and learning how to control their expression are part of the foundation of cell biology and therapeutic development. An efficient and unbiased method to accomplish this is genetic screening, which historically required laborious clone generation and phenotyping and is still limited by scale today. The rapid technological progress on modulating gene function with CRISPR-Cas and measuring it in individual cells has now relaxed the major experimental constraints and enabled pooled screening with complex readouts from single cells. Here, we review the principles and practical considerations for pooled single-cell CRISPR screening. We discuss perturbation strategies, experimental model systems, matching the perturbation to the individual cells, reading out cell phenotypes, and data analysis. Our focus is on single-cell RNA sequencing and cell sorting–based readouts, including image-enabled cell sorting. We expect this transformative approach to fuel biomedical research for the next several decades.
Hear and Now: Ongoing Clinical Trials to Prevent Drug-Induced Hearing Loss
Authors: Lee John , Fernandez Katharine , Cunningham Lisa L.
Published: August 2023

Each year over half a million people experience permanent hearing loss caused by treatment with therapeutic drugs with ototoxic side effects. There is a major unmet clinical need for therapies that protect against this hearing loss without reducing the therapeutic efficacy of these lifesaving drugs. At least 17 clinical trials evaluating 10 therapeutics are currently underway for therapies aimed at preventing aminoglycoside- and/or cisplatin-induced ototoxicity. This review describes the preclinical and clinical development of each of these approaches, provides updates on the status of ongoing trials, and highlights the importance of appropriate outcome measures in trial design and the value of reporting criteria in the dissemination of results.
Impact of sleep on chronobiology of micturition among healthy older adults
Authors: Tyagi Shachi , Resnick Neil M. , Clarkson Becky D. , Zhang Gehui , Krafty Robert T. , Perera Subashan , Subramanya Arohan R. , Buysse Daniel J.
Published: August 2023

Nocturia (waking to void) is the most common cause of sleep interruption among older adults, and increased nighttime urine production is its primary etiology. We showed that in healthy older adults sleep affects the 24-h secretory rhythm of hormones that regulate salt-water balance, which potentially alters nighttime urine output. Further studies are needed to elucidate the impact of chronic insomnia on the secretory rhythms of these hormones.
Amiloride evokes significant natriuresis and weight loss in kidney transplant recipients with and without albuminuria
Authors: Hinrichs Gitte Rye , Nielsen Jette Rude , Birn Henrik , Bistrup Claus , Jensen Boye Lagerbon
Published: August 2023

Amiloride has a significant natriuretic effect in kidney transplant recipients (KTRs) that relates to urinary albumin excretion. The epithelial Na+ channel may be a relevant direct pharmacological target to counter Na+ retention and hypertension in KTRs. Epithelial Na+ channel blockers should be further investigated as a mean to mitigate Na+ and water retention and to potentially obtain optimal blood pressure control in KTRs.
Thirty years of the NaCl cotransporter: from cloning to physiology and structure
Authors: Gamba Gerardo
Published: August 2023

The primary structure of the thiazide-sensitive NaCl cotransporter (NCC) was resolved 30 years ago by the molecular identification of the cDNA encoding this cotransporter, from the winter’s flounder urinary bladder, following a functional expression strategy. This review outlines some aspects of how the knowledge about thiazide diuretics and NCC evolved, the history of the cloning process, and the expansion of the SLC12 family of electroneutral cotransporters. The diseases associated with activation or inactivation of NCC are discussed, as well as the molecular model by which the activity of NCC is regulated. The controversies in the field are discussed as well as recent publication of the three-dimensional model of NCC obtained by cryo-electron microscopy, revealing not only the amino acid residues critical for Na+ and Cl− translocation but also the residues critical for polythiazide binding to the transporter, opening the possibility for a new era in thiazide diuretic therapy.
Acute effects of daily step count on postprandial metabolism and resting fat oxidation: a randomized controlled trial
Authors: Rogers Emily M. , Banks Nile F. , Jenkins Nathaniel D. M.
Published: August 2023

This randomized controlled trial demonstrated that walking 10,000, compared with 2,000, steps/day significantly reduced postprandial lipemia (PPL), an independent predictor of cardiovascular disease (CVD) following same-day evening meal consumption. These experimental data support walking 10,000 steps/day to lower CVD risk.
Skeletal muscle endurance declines with impaired mitochondrial respiration and inadequate supply of acetyl-CoA during muscle fatigue in 5/6 nephrectomized rats
Authors: Fusagawa Hiroyori , Sato Tatsuya , Yamada Takashi , Ashida Yuki , Kimura Iori , Naito Azuma , Tokuda Nao , Yamauchi Nao , Ichise Nobutoshi , Terashima Yoshinori , Ogon Izaya , Teramoto Atsushi , Yamashita Toshihiko , Tohse Noritsugu
Published: August 2023

Mitochondrial dysfunction is associated with decreased skeletal muscle endurance in chronic kidney disease (CKD), but the muscle physiological phenotype and major changes in intramuscular metabolites during muscle fatigue in CKD-related cachexia remain unclear. By using a 5/6 nephrectomized CKD rat model, the present study revealed that CKD is associated with reduced tetanic force in response to repetitive stimuli in a subacute phase, impaired mitochondrial respiration, and inadequate supply of acetyl-CoA during muscle fatigue.
Intermittent hypoxia: a call for harmonization in terminology
Authors: Panza Gino S. , Burtscher Johannes , Zhao Fei
Published: August 2023

Mild intermittent hypoxia may be a potent novel strategy to improve cardiovascular function, motor and cognitive function, and altitude acclimatization. However, there is still a stigma surrounding the field of intermittent hypoxia (IH). Major contributors to this stigma may be due to the overlapping terminology, heterogeneous methodological approaches, and an almost dogmatic focus on different mechanistic underpinnings in different fields of research. Many clinicians and investigators explore the pathophysiological outcomes following long-term exposure to IH in an attempt to improve our understanding of sleep apnea (SA) and develop new treatment plans. However, others use IH as a tool to improve physiological outcomes such as blood pressure, motor function, and altitude acclimatization. Unfortunately, studies investigating the pathophysiology of SA or the potential benefit of IH use similar, unstandardized terminologies facilitating a confusion surrounding IH protocols and the intentions of various studies. In this perspective paper, we aim to highlight IH terminology-related issues with the aim of spurring harmonization of the terminology used in the field of IH research to account for distinct outcomes of hypoxia exposure depending on protocol and individuum.
Characterization of cerebral macro- and microvascular hemodynamics during transient hypotension
Authors: Shoemaker Leena N. , Milej Daniel , Sajid Aleena , Mistry Jigneshkumar , Lawrence Keith St , Shoemaker J. Kevin
Published: August 2023

To characterize the relationship between cerebrovascular patterns within the large middle cerebral artery (MCA) and a downstream microvascular segment, we used a novel combination of transcranial Doppler ultrasound of the MCA and optical monitoring of a downstream microvascular segment, respectively, under conditions of transiently reduced mean arterial pressure (i.e., lower body negative pressure, −80 mmHg). A rapid increase in vessel compliance accompanied the maintenance of MCA blood velocity and downstream microvascular flow.
Lung endothelium, tau, and amyloids in health and disease
Authors: Balczon Ron , Lin Mike T. , Voth Sarah , Nelson Amy R. , Schupp Jonas C. , Wagener Brant M. , Pittet Jean-Francois , Stevens Troy
Published: August 2023

Lung endothelia in the arteries, capillaries, and veins are heterogeneous in structure and function. Lung capillaries in particular represent a unique vascular niche, with a thin yet highly restrictive alveolar-capillary barrier that optimizes gas exchange. Capillary endothelium surveys the blood while simultaneously interpreting cues initiated within the alveolus and communicated via immediately adjacent type I and type II epithelial cells, fibroblasts, and pericytes. This cell-cell communication is necessary to coordinate the immune response to lower respiratory tract infection. Recent discoveries identify an important role for the microtubule-associated protein tau that is expressed in lung capillary endothelia in the host-pathogen interaction. This endothelial tau stabilizes microtubules necessary for barrier integrity, yet infection drives production of cytotoxic tau variants that are released into the airways and circulation, where they contribute to end-organ dysfunction. Similarly, beta-amyloid is produced during infection. Beta-amyloid has antimicrobial activity, but during infection it can acquire cytotoxic activity that is deleterious to the host. The production and function of these cytotoxic tau and amyloid variants are the subject of this review. Lung-derived cytotoxic tau and amyloid variants are a recently discovered mechanism of end-organ dysfunction, including neurocognitive dysfunction, during and in the aftermath of infection.
Chemical, Physical, and Technological Characteristics of Palm Olein and Canola Oil Blends
Authors: Allam Ayman Younes , Khan Zakir Showkat , Bhat Mohmad Sayeed , Naik Bindu , Wani Sajad Ahmad , Rustagi Sarvesh , Aijaz Tahmeed , Elsadek Mohamed Farouk , Chen Tse-Wei
Published: August 2023

Because of the limited technical properties of their native forms, oils and fats are frequently blended to achieve the desired textural and oxidative properties. In this study, canola and palm oil blends were prepared in nine different proportions: B1 (90 : 10), B2 (80 : 20), B3 (70 : 30), B4 (60 : 40), B5 (50 : 50), B6 (40 : 60), B7 (30 : 70), B8 (20 : 80), and B9 (10 : 90). Pure palm oil (PO) and canola oil (CO) were used as the controls. All blends were assessed for physicochemical properties, fatty acid composition, heat treatment, and polymer content. The results indicated negative cold tests only for B1 and B2 blends with 10 and 20% PO, respectively. Iodine value decreased with increasing palm oil concentration and was lowest (62.03 ± 0.526) for blend B9, i.e., 90% PO. The fatty acid profile indicated more saturated fatty acids and a higher percentage of oleic acid in PO than in CO. The fatty acid profile values of blends B1–B9 were between those of the pure PO and CO. Linoleic and linolenic acids were more in blends B1–B9 than those in pure PO. The polymer content of PO (7.17%) was found to be lower than that of CO (10.32%) after 60 h of heating at 180°C. In addition, biologically active substances (BASs), which could be formed during the frying process, were tested by measuring the inhibition zone of E. coli growth. PO retarded BAS formation. The blended palm or canola oils resulted in better stability and increased organoleptic characteristics and hence can be suitable as economical and healthy alternatives to pure palm or canola oil.
A New Nomogram for Predicting 30-Day In-Hospital Mortality Rate of Acute Cholangitis Patients in the Intensive Care Unit
Authors: Pan Li-Na , Pan Shen-Ao , Hong Guang-Liang , Chen Kun-Wei
Published: August 2023

Purpose. Acute cholangitis (AC) is a widespread acute inflammatory disease and the main cause of septic shock, which has a high death rate in hospitals. At present, the prediction models for short-term mortality of AC patients are still not ideal. We aimed at developing a new model that could forecast the short-term mortality rate of AC patients. Methods. Data were extracted from the Medical Information Mart for Intensive Care IV version 2.0 (MIMIC-IV v2.0). There were a total of 506 cases of AC patients that were included. Patients were given a 7 : 3 split between the training set and the validation set after being randomly assigned to one of the groups. Multivariate logistic regression was used to create an AC patient predictive nomogram for 30-day mortality. The overall efficacy of the model is evaluated using the area under the receiver operating characteristic curve (AUC), the calibration curve, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), and a decision curve analysis (DCA). Results. Out of 506 patients, 14.0% (71 patients) died. The training cohort had 354 patients, and the validation cohort had 152 patients. GCS, SPO2, albumin, AST/ALT, glucose, potassium, PTT, and peripheral vascular disease were the independent risk factors according to the multivariate analysis results. The newly established nomogram had better prediction performance than other common scoring systems (such as SOFA, OASIS, and SAPS II). For two cohorts, the calibration curve demonstrated coherence between the nomogram and the ideal observation

P
 
>
 
0.05

. The clinical utility of the nomogram in both sets was revealed by decision curve analysis. Conclusion. The novel prognostic model was effective in forecasting the 30-day mortality rate for acute cholangitis patients.
HDACi-dependent Microenvironmental Normalization Overcomes Tumor Burden–induced T-cell Exhaustion
Authors: Nguyen Andrew , Brown Dominique , Krishnan Ramya , Bastin Donald , Deng Li , Chen Lan , Salem Omar , Walsh Scott R. , Bramson Jonathan L. , Wan Yonghong
Published: August 2023

Purpose:

T-cell exhaustion limits immunotherapy for the treatment of solid tumors. Although immune checkpoint blockade and adoptive T-cell therapy (ACT) can mediate tumor regression, their potency is often determined by tumor burden. Here, we identified tumor burden–related pathway changes that are conducive to T-cell exhaustion. We then determined whether microenvironmental reprogramming via epigenetic modulation could reverse T-cell exhaustion and improve immunotherapeutic responsiveness.

Experimental Design:

We developed a murine syngeneic tumor model wherein an increased burden ablated therapeutic responsiveness to ACT, which corresponded with systemic induction of T-cell exhaustion. Transcriptome analysis of these large tumors allowed us to characterize changes to immunosuppressive pathway expression during class I histone deacetylase inhibitor MS-275 treatment. We then measured the therapeutic impact of MS-275 during ACT and assessed T-cell exhaustion by transcriptome/phenotypic analysis.

Results:

ACT durably regressed small tumors but failed to control large tumors, which were associated with systemic T-cell exhaustion and ablation of T-cell responses. Large tumors were defined by an immunosuppressive pathway signature. MS-275 reversed this pathway signature and promoted durable regression of large tumors during ACT. Prototypical exhaustion marker Tim-3 was selectively upregulated in transferred T cells despite displaying a reduced exhaustion signature. Instead, we observed enhanced activation-dependent signaling correlating with enrichment of the IL2–STAT5 signaling axis. Activated CD8+ T-cell responses were predominantly skewed toward terminal effector cell–like CD44+ Tim-3hi TCF1− CD127− KLRG1+ differentiation.

Conclusions:

Tumor burden–induced pathway changes can be reversed through epigenetic reprogramming, enabling the conversion from T-cell exhaustion to effector lineage differentiation.
Table S4 from Pan-Cancer Pharmacogenomic Analysis of Patient-Derived Tumor Cells Using Clinically Relevant Drug Exposures
Authors: Chang Stephen H. , Ice Ryan J. , Chen Michelle , Sidorov Maxim , Woo Rinette W.L. , Rodriguez-Brotons Aida , Jian Damon , Kim Han Kyul , Kim Angela , Stone David E. , Nazarian Ari , Oh Alyssia , Tranah Gregory J. , Nosrati Mehdi , de Semir David , Dar Altaf A. , Desprez Pierre-Yves , Kashani-Sabet Mohammed , Soroceanu Liliana , McAllister Sean D.
Published: August 2023

Supplementary Table 4 LOBICO PDXC % sens vs insens