bluuebunny/crossref_metadata_2025 huggingface dataset:
J.S. Mill's Puzzling Position on Prostitution and his Harm Principle
Authors: Tunick Mark
Published: October 2023

J.S. Mill argues against licensing or forced medical examinations of prostitutes even if these would reduce harm, for two reasons: the state should not legitimize immoral conduct; and coercing prostitutes would violate Mill's harm principle as they do not risk causing non-consensual harm to others, their clients do. There is nothing puzzling about Mill opposing coercive restrictions on self-regarding immoral conduct while also opposing state support of that conduct. But why does Mill oppose restrictions on prostitutes’ liberty if those restrictions could prevent harm to third parties? Mill's position is not puzzling once we recognize that his harm principle is not a harm-prevention principle that warrants restrictions on liberty to prevent harm no matter who caused it (as David Lyons famously argued) but instead warrants restrictions on liberty only of individuals who are the morally relevant cause of that harm. Mill's discussion of prostitution shows he prioritizes both individuality and moral progress over harm reduction.
Violations of the heart: Parental harm in war and oppression
Authors: Friedman Rebekka , Ketola Hanna
Published: October 2023

This article examines ‘parental harm’ – a harm that occurs when a parent loses or faces the threat of losing a child. We contend that the manipulation and severing of relationships between parents and children has played a central role in war and oppression across historical contexts. Parental harm has long-term and pervasive effects and results in complex legacies for carers and their communities. Despite its grave impact, there is little research within International Relations into parental harm and understanding of its effects. We conceptualise parental harm through two frames – the ‘harm of separation’ and ‘harm to the ability to parent’ – and theorise gendered dimensions of how it is perpetuated and experienced. As such, we advance feminist understandings of family as a gendered institution that shapes the conduct of war and institutionalises racialised oppression. Our conception of parental harm offers novel insights into the relationship between intimate relations, the family, and state power and practices. We illustrate our conceptual arguments through two examples: the control and manipulation of family in antebellum slavery in the United States and the targeting of Tamil children in disappearances in Sri Lanka. These examples demonstrate the pervasiveness of parental harm across contexts and forms of violence.
Attribution of nosocomial seeding to long-term care facility COVID-19 outbreaks
Authors: Flannagan Joe , Chudasama Dimple Y , Hope Russell , Collin Simon M , Bhattacharya Alex , Merrick Rachel , Aziz Nurin Abdul , Hopkins Susan , Dabrera Gavin , Lamagni Theresa
Published: October 2023

Residents of long-term care facilities (LTCFs) were disproportionately affected by the COVID-19 pandemic. We assessed the extent to which hospital-associated infections contributed to COVID-19 LTCF outbreaks in England. We matched addresses of cases between March 2020 and June 2021 to reference databases to identify LTCF residents. Linkage to health service records identified hospital-associated infections, with the number of days spent in hospital before positive specimen date used to classify these as definite or probable. Of 149,129 cases in LTCF residents during the study period, 3,748 (2.5%) were definite or probable hospital-associated and discharged to an LTCF. Overall, 431 (0.3%) were identified as index cases of potentially nosocomial-seeded outbreaks (2.7% (431/15,797) of all identified LTCF outbreaks). These outbreaks involved 4,521 resident cases and 1,335 deaths, representing 3.0% and 3.6% of all cases and deaths in LTCF residents, respectively. The proportion of outbreaks that were potentially nosocomial-seeded peaked in late June 2020, early December 2020, mid-January 2021, and mid-April 2021. Nosocomial seeding contributed to COVID-19 LTCF outbreaks but is unlikely to have accounted for a substantial proportion. The continued identification of such outbreaks after the implementation of preventative policies highlights the challenges of preventing their occurrence.
The HAM-D6 through the lens of grief: Clinical considerations for administering the six-item Hamilton Depression Rating Scale in the context of bereavement
Authors: Goldman Maya , Napolitano Stephanie , Roberts Kailey E. , Lichtenthal Wendy G.
Published: October 2023

Objectives

Diagnosing mental health challenges in bereavement is controversial; however, regardless of one’s position on this matter, assessments of bereaved individuals continue to occur in clinical and research contexts. It is critical for evaluations to account for contextual factors that are unique to bereavement. This paper summarizes considerations for diagnosing depression in bereaved individuals, focusing on use of the six-item Hamilton Depression Rating Scale (HAM-D6).

Methods

Following a literature review of the Hamilton Depression Rating Scale (HAM-D) and various versions, we summarized decision rules we used in scoring the HAM-D6 in a study of parents bereaved by cancer. We expanded on existing scoring guidelines for each of the HAM-D6 items, including depressed mood, work and activities, general somatic symptoms, guilt, psychic anxiety, and psychomotor retardation, and illustrated clinical distinctions and probes for assessors to consider through case examples from our research with bereaved parents.

Results

Considerations for assessing depressive symptoms and behavior changes in the context of bereavement were summarized. Symptoms that may be diagnostic of depression in some populations may reflect other factors in the bereaved, such as a change in priorities, social expectations surrounding grief, or avoidance of grief activators. Nuanced factors are important for assessors to consider when administering the HAM-D6 to bereaved individuals.

Significance of results

Our sharing of these considerations is not intended to promote diagnosis of depression in bereavement but to highlight the unique contextual factors that distinguish symptoms of depression from common experiences of grievers when applying an assessment tool such as the HAM-D6. While validated measures can be constraining, they can have clinical utility; they may increase standardization in research, help clinicians communicate with each other, advance the field more generally to understand the varying struggles bereaved individuals experience, and systemically facilitate access to services via managed care.
How are psychological factors involved in the evaluation and treatment of sleep and circadian rhythm disorders?
Authors: Kay Daniel B. , Dzierzewski Joseph M.
Published: October 2023

Clinical sleep psychology is a branch of psychological science that aims to understand and harness psychological factors (i.e., affective, behavioral, cognitive, social, and environmental) that are involved in sleep and circadian disorders. Behavioral Sleep Medicine, a branch of sleep medicine, has a similar focus (https://www.behavioralsleep.org/). Collectively, these clinical branches of sleep psychology aim to effectively evaluate and treat sleep and circadian rhythm disorders to promote sleep health. Clinical sleep psychology has a long history, including early work in the areas of insomnia, behavioral treatment for pediatric sleep disorders, dream psychology, and hypnotic sleep (Jacobson 1934; McReynolds 1997; Mower and Mower 1938; Münsterberg 1915; Watson 1928). The past 100 years have seen considerable progress in identifying psychological factors involved in sleep and circadian rhythm disorders and their treatment, particularly in insomnia and pediatric sleep disorders. Barriers to advancement persist.
Calibration of Sr/Ca Ratio and In Situ Temperature Using Hawaiian Corals
Authors: Uchiyama Ryohei , Watanabe Tsuyoshi , Kahng Samuel E. , Yamazaki Atsuko
Published: October 2023

The Sr/Ca ratio of modern coral skeletons can record local seawater temperature (T) and is an important tool for reconstructing past environments. However, site‐specific calibrations are required to ensure accurate temperature reconstructions. Here, we examine three modern coral skeletons collected at contrasting sites on the island of Oahu, Hawaii to establish the first accurate calibrations for this region and investigate site specific influences on the calibration process. Satellite T data, which is used for many calibrations, may not be able to derive an accurate thermometer. For our shallow lagoonal sites, satellite T had smaller seasonal T ranges, which resulted in significantly higher slopes of Sr/Ca‐T compared to using in situ T. The traditional age model based on aligning only min/max values can lead to errors in the Sr/Ca‐T calibration due to variable growth rates. An enhanced age model which adds midpoint alignments between the min/max peak values can account for seasonal changes in growth rate and reduce the error. On the same island, site‐ and time period specific conditions can cause notable differences in the Sr/Ca‐T calibrations. The coral from an estuarine embayment showed a high Sr/Ca offset, likely due to high Sr/Ca in ambient seawater. For corals which experienced thermal stress, lower slopes were observed probably due to elevated Sr/Ca values during the period of thermal stress.
Anthropogenic and Biogenic Sources Drive the Molecular Fingerprints and Atmospheric Processing of Water‐Soluble Organic Aerosols at a Tropical Hill Station in the Western Ghats of India
Authors: Deshmukh Dhananjay K. , Aswini A. R. , Ramya C. B. , Hegde Prashant , Babu S. Suresh
Published: October 2023

The widespread presence of organic aerosols (OA) in the atmosphere and their dominant role in climate forcing are increasingly recognized. Measurements from the high‐altitude region provide insights into the natural processes and long‐range transport of aerosols. We studied water‐soluble organic compounds in PM1.1 during January‐March 2020 and February‐April 2021 at Ponmudi (8.8°N and 77.1°E), a tropical hill station (960 m a.s.l.) located on the Western Ghats of India. The 5‐day backward trajectories of air masses presented that continental and marine sources impacted the site during the campaign, and thus we classified samples as mixed and marine air masses. Their molecular fingerprints revealed the prevalence of oxalic acid (C2), followed by terephthalic acid in mixed air mass and malonic (C3) or succinic (C4) acid in maritime air mass aerosol samples. This feature and the phthalic to azelaic acid ratio, as well as the C3 to C4 and fumaric to maleic acid ratios, evidenced that water‐soluble OA were of anthropogenic origin and less photochemically aged in mixed air mass samples, whereas they derived from biogenic sources and more photochemical aging in marine air mass samples. However, we found their comparable contributions in water‐soluble organic carbon under mixed and marine air masses. Linear correlations between C2 relative abundance and its ratios with the precursor compounds implied that the oxidation of precursors to oxalic acid occurs during atmospheric transport. The results revealed that the input of anthropogenic and biogenic precursors followed by atmospheric processing controlled the burden of water‐soluble OA across the Western Ghats.
Weekly Forecasting of Yellow Fever Occurrence and Incidence via Eco‐Meteorological Dynamics
Authors: Servadio Joseph L. , Convertino Matteo , Fiecas Mark , Muñoz‐Zanzi Claudia
Published: October 2023

Yellow Fever (YF), a mosquito‐borne disease, requires ongoing surveillance and prevention due to its persistence and ability to cause major epidemics, including one that began in Brazil in 2016. Forecasting based on factors influencing YF risk can improve efficiency in prevention. This study aimed to produce weekly forecasts of YF occurrence and incidence in Brazil using weekly meteorological and ecohydrological conditions. Occurrence was forecast as the probability of observing any cases, and incidence was forecast to represent morbidity if YF occurs. We fit gamma hurdle models, selecting predictors from several meteorological and ecohydrological factors, based on forecast accuracy defined by receiver operator characteristic curves and mean absolute error. We fit separate models for data before and after the start of the 2016 outbreak, forecasting occurrence and incidence for all municipalities of Brazil weekly. Different predictor sets were found to produce most accurate forecasts in each time period, and forecast accuracy was high for both time periods. Temperature, precipitation, and previous YF burden were most influential predictors among models. Minimum, maximum, mean, and range of weekly temperature, precipitation, and humidity contributed to forecasts, with optimal lag times of 2, 6, and 7 weeks depending on time period. Results from this study show the use of environmental predictors in providing regular forecasts of YF burden and producing nationwide forecasts. Weekly forecasts, which can be produced using the forecast model developed in this study, are beneficial for informing immediate preparedness measures.
Population Exposure Changes to Mean and Extreme Climate Events Over Pakistan and Associated Mechanisms
Authors: Saleem Farhan , Zhang Wenxia , Hina Saadia , Zeng Xiaodong , Ullah Irfan , Bibi Tehmina , Nnamdi Dike Victor
Published: October 2023

The increasing prevalence of warmer trends and climate extremes exacerbate the population's exposure to urban settlements. This work investigated population exposure changes to mean and extreme climate events in different Agro‐Ecological Zones (AEZs) of Pakistan and associated mechanisms (1979−2020). Spatiotemporal trends in mean and extreme temperatures revealed significant warming mainly over northern, northeastern, and southern AEZs. In contrast, mean‐to‐extreme precipitation changes showed non‐uniform patterns with a significant increase in the northeast AEZs. Population exposure to mean (extreme) temperature and precipitation events increased two‐fold during 2000–2020. The AEZs in urban settlements (i.e., Indus Delta, Northern Irrigated Plain, and Barani/Rainfall) show a maximum exposure to extreme temperatures of about 70–100 × 106 (person‐days) in the reference period (1979−1999), which increases to 140–200 × 106 person‐days in the recent period (2000−2020). In addition, the highest exposure to extreme precipitation days also increases to 40–200 × 106 person‐days during 2000–2020 than 1979−1999 (20–100 × 106) person‐days. Relative changes in exposure are large (60%–90%) for the AEZs across northeast Pakistan, justifying the spatial population patterns over these zones. Overall, the observed changes in exposure are primarily attributed to the climate effect (50%) over most AEZs except Northern Irrigated Plain for R10 and R20 events, where the interaction effect takes the lead. The population exposure rapidly increased over major AEZs of Pakistan, which could be more vulnerable to extreme events due to rapid urbanization and population growth in the near future.
How can Changes in the Human‐Flood Distance Mitigate Flood Fatalities and Displacements?
Authors: Wang Ning , Sun Fubao , Koutsoyiannis Demetris , Iliopoulou Theano , Wang Tingting , Wang Hong , Liu Wenbin , Sargentis G.‐Fivos , Dimitriadis Panayiotis
Published: October 2023

Comprehending the correlation between alterations in human‐flood distance and flood fatalities (as well as displacements) is pivotal for formulating effective human adaptive strategies in response to floods. However, this relationship remains inadequately explored in existing global analyses. To address this gap, we examine 910 flood events occurring from 2000 to 2018, resulting in significant numbers of fatalities and displacements. We find that in 53% of countries, humans tend to distance from floods, particularly in the Middle East. Such distancing greatly mitigates flood fatalities and displacements. Simultaneously, in areas with increased flood protection level (FPL), humans are less likely to move away from floods. Furthermore, FPL and human‐flood distance have decreased in regions affected by ice jam‐ and hurricane‐induced floods from 2000 to 2018. Notably, regions with human‐flood distance slightly below the average for a given flood type experience more severe flood fatalities.
Detecting the Preparatory Phase of Induced Earthquakes at The Geysers (California) Using K‐Means Clustering
Authors: Iaccarino A. G. , Picozzi M.
Published: October 2023

The generation of strong earthquakes is a long‐debated problem in seismology, and its importance is increased by the possible implications for earthquake forecasting. It is hypothesized that the earthquake generation processes are anticipated by several phenomena occurring within a nucleation region. These phenomena, also defined as preparatory processes, load stress on the fault leading it to reach a critical state. In this paper, we investigate the seismicity preceding 19 moderate (Mw ≥ 3.5) earthquakes at The Geysers, Northern California, aiming to verify the existence of a preparatory phase before their occurrence. We apply an unsupervised K‐means clustering technique to analyze time series of physics‐related features extracted from catalog information and estimated for events occurred before the mainshocks. Specifically, we study the temporal evolution of the b‐value from the Gutenberg‐Richter (b), the magnitude of completeness (Mc), the fractal dimension (Dc), the inter‐event time (dt), and the moment rate (). Our analysis shows that out of 19 moderate magnitude events considered, a common preparatory phase for 11 events is clearly identified, plus other five events for which we can guess a preparatory phase but with different characteristics from the previous ones. The latter result confirms that even within the same tectonic context different possible activation behaviors may exist. The duration of the preparatory process ranges between about 16 hr and 4 days. We observe that also for the retrieved preparatory process a decrease in b, Mc, and Dc, and an increase of . Finally, we show a clear correlation between events with a preparation phase and the location of injection's wells, suggesting an important role of fluids in the preparatory process.
Comparison of Eddy Dissipation Rate Estimated From Operational Radiosonde and Commercial Aircraft Observations in the United States
Authors: Ko Han‐Chang , Chun Hye‐Yeong , Sharman Robert D. , Kim Jung‐Hoon
Published: October 2023

The one‐third power of the energy dissipation rate (EDR), a primary aviation turbulence metric, is calculated using high vertical‐resolution radiosonde data (HVRRD) and compared with flight‐EDR observed from commercial airlines. Comparisons are made along the main flight routes over the United States and at z = 20–45 kft for 6 years (2012–2017). The horizontal distributions of moderate‐or‐greater (MOG) ratio of HVRRD‐EDR show large values over the Rocky Mountains, consistent with those of flight‐EDR. Vertically, the MOG ratios of HVRRD‐EDR show local peaks at z = 20–23 kft and 41–44 kft, while those of flight‐EDR at z = 23–26 kft and 35–41 kft. Temporally, HVRRD‐EDR has maximum MOG values in JJA and minimum values in DJF at z = 20–30 kft, which is opposite to the flight‐EDR. At z = 30–40 kft, HVRRD‐EDR shows nearly no seasonal variation but flight‐EDR has large values in MAM and small values in JJA. At z = 40–45 kft, HVRRD‐EDR (flight‐EDR) shows large values in MAM and small values in SON (DJF). Discrepancies in spatiotemporal distributions between the two data sets likely stem from: (a) turbulence observed from the two data sets cannot be the same event, (b) the limitation of HVRRD‐EDR in capturing shear‐instability under statically stable condition (i.e., Kelvin‐Helmholtz instability) which probably accounts for most flight‐EDR events at upper levels, and (c) limitation in aircraft measurements response to fluctuations at smaller scales than the aircraft size.
Personalised lung cancer risk stratification and lung cancer screening: do general practice electronic medical records have a role?
Authors: Jani Bhautesh Dinesh , Sullivan Michael K. , Hanlon Peter , Nicholl Barbara I. , Lees Jennifer S. , Brown Lamorna , MacDonald Sara , Mark Patrick B. , Mair Frances S. , Sullivan Frank M.
Published: October 2023

Background

In the United Kingdom (UK), cancer screening invitations are based on general practice (GP) registrations. We hypothesize that GP electronic medical records (EMR) can be utilised to calculate a lung cancer risk score with good accuracy/clinical utility.

Methods

The development cohort was Secure Anonymised Information Linkage-SAIL (2.3 million GP EMR) and the validation cohort was UK Biobank-UKB (N = 211,597 with GP-EMR availability). Fast backward method was applied for variable selection and area under the curve (AUC) evaluated discrimination.

Results

Age 55–75 were included (SAIL: N = 574,196; UKB: N = 137,918). Six-year lung cancer incidence was 1.1% (6430) in SAIL and 0.48% (656) in UKB. The final model included 17/56 variables in SAIL for the EMR-derived score: age, sex, socioeconomic status, smoking status, family history, body mass index (BMI), BMI:smoking interaction, alcohol misuse, chronic obstructive pulmonary disease, coronary heart disease, dementia, hypertension, painful condition, stroke, peripheral vascular disease and history of previous cancer and previous pneumonia. The GP-EMR-derived score had AUC of 80.4% in SAIL and 74.4% in UKB and outperformed ever-smoked criteria (currently the first step in UK lung cancer screening pilots).

Discussion

A GP-EMR-derived score may have a role in UK lung cancer screening by accurately targeting high-risk individuals without requiring patient contact.
ZNF281 inhibits mitochondrial biogenesis to facilitate metastasis of hepatocellular carcinoma
Authors: Zhao Qingfang , Zhang Chenguang , Zhang Xialu , Wang Shanshan , Guo Ting , Yin Yuzhe , Zhang Hui , Li Zhuo , Si Yang , Lu Yabin , Cheng Shan , Ding Wei
Published: October 2023

Zinc finger protein 281 (ZNF281) has been shown to promote tumor progression. However, the underlying mechanism remains to be further elucidated. In this study, ZNF281 knockdown increased the expression of mitochondrial transcription factor A (TFAM) in hepatocellular carcinoma (HCC) cells, accompanied with increment of mitochondrial content, oxygen consumption rate (OCR) and levels of TCA cycle intermetabolites. Mechanistic investigation revealed that ZNF281 suppressed the transcription of TFAM, nuclear respiratory factor 1 (NRF1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Furthermore, ZNF281 interacted with NRF1 and PGC-1α, and was recruited onto the promoter regions of TFAM, TFB1M and TFB2M repressing their expression. Knockdown of TFAM reversed ZNF281 depletion induced up-regulation of mitochondrial biogenesis and function, as well as impaired epithelial mesenchymal transition, invasion and metastasis of HCC cells. Our research uncovered a novel suppressive function of ZNF281 on mitochondrial biogenesis through inhibition of the NRF1/PGC-1α-TFAM axis, which may hold therapeutic potentials for HCC.
Cigarette smoke causes a bioenergetic crisis in RPE cells involving the downregulation of HIF-1α under normoxia
Authors: Henning Yoshiyuki , Willbrand Katrin , Larafa Safa , Weißenberg Gesa , Matschke Veronika , Theiss Carsten , Görtz Gina-Eva , Matschke Johann
Published: October 2023

Age-related macular degeneration (AMD) is the most common blinding disease in the elderly population. However, there are still many uncertainties regarding the pathophysiology at the molecular level. Currently, impaired energy metabolism in retinal pigment epithelium (RPE) cells is discussed as one major hallmark of early AMD pathophysiology. Hypoxia-inducible factors (HIFs) are important modulators of mitochondrial function. Moreover, smoking is the most important modifiable risk factor for AMD and is known to impair mitochondrial integrity. Therefore, our aim was to establish a cell-based assay that enables us to investigate how smoking affects mitochondrial function in conjunction with HIF signaling in RPE cells. For this purpose, we treated a human RPE cell line with cigarette smoke extract (CSE) under normoxia (21% O2), hypoxia (1% O2), or by co-treatment with Roxadustat, a clinically approved HIF stabilizer. CSE treatment impaired mitochondrial integrity, involving increased mitochondrial reactive oxygen species, disruption of mitochondrial membrane potential, and altered mitochondrial morphology. Treatment effects on cell metabolism were analyzed using a Seahorse Bioanalyzer. Mitochondrial respiration and ATP production were impaired in CSE-treated cells under normoxia. Surprisingly, CSE-treated RPE cells also exhibited decreased glycolytic rate under normoxia, causing a bioenergetic crisis, because two major metabolic pathways that provide ATP were impaired by CSE. Downregulation of glycolytic rate was HIF-dependent because HIF-1α, the α-subunit of HIF-1, was downregulated by CSE on the protein level, especially under normoxia. Moreover, hypoxia incubation and treatment with Roxadustat restored glycolytic flux. Taken together, our in vitro model provides interesting insights into HIF-dependent regulation of glycolysis under normoxic conditions, which will enable us to investigate signaling pathways involved in RPE metabolism in health and disease.
Pasteurella sp. associated with fatal septicaemia in six African elephants
Authors: Foggin Chris M. , Rosen Laura E. , Henton Marijke M. , Buys Angela , Floyd Toby , Turner Andrew D. , Tarbin Jonathan , Lloyd Antony S. , Chaitezvi Columbas , Ellis Richard J. , Roberts Helen C. , Dastjerdi Akbar , Nunez Alejandro , van Vliet Arnoud H. M. , Steinbach Falko
Published: October 2023

The sudden mortality of African elephants (Loxodonta africana) in Botswana and Zimbabwe in 2020 provoked considerable public interest and speculation. Poaching and malicious poisoning were excluded early on in the investigation. Other potential causes included environmental intoxication, infectious diseases, and increased habitat stress due to ongoing drought. Here we show evidence of the mortalities in Zimbabwe as fatal septicaemia associated with Bisgaard taxon 45, an unnamed close relative of Pasteurella multocida. We analyse elephant carcasses and environmental samples, and fail to find evidence of cyanobacterial or other intoxication. Post-mortem and histological findings suggest a bacterial septicaemia similar to haemorrhagic septicaemia caused by P. multocida. Biochemical tests and 16S rDNA analysis of six samples and genomic analysis of one sample confirm the presence of Bisgaard taxon 45. The genome sequence contains many of the canonical P. multocida virulence factors associated with a range of human and animal diseases, including the pmHAS gene for hyaluronidase associated with bovine haemorrhagic septicaemia. Our results demonstrate that Bisgaard taxon 45 is associated with a generalised, lethal infection and that African elephants are susceptible to opportunistically pathogenic Pasteurella species. This represents an important conservation concern for elephants in the largest remaining metapopulation of this endangered species.
Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization
Authors: Zhang Fang-Ling , Hu Zhen , Wang Yi-Fan , Zhang Wen-Juan , Zhou Bo-Wei , Sun Qi-Shun , Lin Ze-Bin , Liu Ke-Xuan
Published: October 2023

Intestinal organoid transplantation is a promising therapy for the treatment of mucosal injury. However, how the transplanted organoids regulate the immune microenvironment of recipient mice and their role in treating intestinal ischemia-reperfusion (I/R) injury remains unclear. Here, we establish a method for transplanting intestinal organoids into intestinal I/R mice. We find that transplantation improve mouse survival, promote self-renewal of intestinal stem cells and regulate the immune microenvironment after intestinal I/R, depending on the enhanced ability of macrophages polarized to an anti-inflammatory M2 phenotype. Specifically, we report that L-Malic acid (MA) is highly expressed and enriched in the organoids-derived conditioned medium and cecal contents of transplanted mice, demonstrating that organoids secrete MA during engraftment. Both in vivo and in vitro experiments demonstrate that MA induces M2 macrophage polarization and restores interleukin-10 levels in a SOCS2-dependent manner. This study provides a therapeutic strategy for intestinal I/R injury.
Identification of CCZ1 as an essential lysosomal trafficking regulator in Marburg and Ebola virus infections
Authors: Monteil Vanessa , Kwon Hyesoo , John Lijo , Salata Cristiano , Jonsson Gustav , Vorrink Sabine U. , Appelberg Sofia , Youhanna Sonia , Dyczynski Matheus , Leopoldi Alexandra , Leeb Nicole , Volz Jennifer , Hagelkruys Astrid , Kellner Max J. , Devignot Stéphanie , Michlits Georg , Foong-Sobis Michelle , Weber Friedemann , Lauschke Volker M. , Horn Moritz , Feldmann Heinz , Elling Ulrich , Penninger Josef M. , Mirazimi Ali
Published: October 2023

Marburg and Ebola filoviruses are two of the deadliest infectious agents and several outbreaks have occurred in the last decades. Although several receptors and co-receptors have been reported for Ebola virus, key host factors remain to be elucidated. In this study, using a haploid cell screening platform, we identify the guanine nucleotide exchange factor CCZ1 as a key host factor in the early stage of filovirus replication. The critical role of CCZ1 for filovirus infections is validated in 3D primary human hepatocyte cultures and human blood-vessel organoids, both critical target sites for Ebola and Marburg virus tropism. Mechanistically, CCZ1 controls early to late endosomal trafficking of these viruses. In addition, we report that CCZ1 has a role in the endosomal trafficking of endocytosis-dependent SARS-CoV-2 infections, but not in infections by Lassa virus, which enters endo-lysosomal trafficking at the late endosome stage. Thus, we have identified an essential host pathway for filovirus infections in cell lines and engineered human target tissues. Inhibition of CCZ1 nearly completely abolishes Marburg and Ebola infections. Thus, targeting CCZ1 could potentially serve as a promising drug target for controlling infections caused by various viruses, such as SARS-CoV-2, Marburg, and Ebola.
Implementing psychological interventions delivered by respiratory professionals for people with COPD. A stakeholder interview study
Authors: Wileman V. , Rowland V. , Kelly M. , Steed L. , Sohanpal R. , Pinnock H. , Taylor S. J. C.
Published: October 2023

Implementing psychological interventions in healthcare services requires an understanding of the organisational context. We conducted an interview study with UK National Health Service stakeholders to understand the barriers and facilitators for implementing psychological interventions for people with chronic obstructive pulmonary disorder (COPD). We used TANDEM as an exemplar intervention; a psychological intervention recently evaluated in a randomised controlled trial. Twenty participants providing care and/or services to people with COPD were purposively sampled from NHS primary/secondary care, and commissioning organisations. Participants were recruited via professional networks and referrals. Verbatim transcripts of semi-structured interviews were analysed using thematic analysis. Four themes were identified: (1) Living with COPD and emotional distress affects engagement with physical and psychological services; (2) Resource limitations affects service provision in COPD; (3) Provision of integrated care is important for patient well-being; and (4) Healthcare communication can be an enabler or a barrier to patient engagement. People need support with physical and psychological symptoms inherent with COPD and healthcare should be provided holistically. Respiratory healthcare professionals are considered able to provide psychologically informed approaches, but resources must be available for training, staff supervision and service integration. Communication between professionals is vital for clear understanding of an intervention’s aims and content, to facilitate referrals and uptake. There was widespread commitment to integrating psychological and physical care, and support of respiratory healthcare professionals’ role in delivering psychological interventions but significant barriers to implementation due to concerns around resources and cost efficiency. The current study informs future intervention development and implementation.
Quantum logic gate synthesis as a Markov decision process
Authors: Alam M. Sohaib , Berthusen Noah F. , Orth Peter P.
Published: October 2023

Reinforcement learning has witnessed recent applications to a variety of tasks in quantum programming. The underlying assumption is that those tasks could be modeled as Markov decision processes (MDPs). Here, we investigate the feasibility of this assumption by exploring its consequences for single-qubit quantum state preparation and gate compilation. By forming discrete MDPs, we solve for the optimal policy exactly through policy iteration. We find optimal paths that correspond to the shortest possible sequence of gates to prepare a state or compile a gate, up to some target accuracy. Our method works in both the absence and presence of noise and compares favorably to other quantum compilation methods, such as the Ross–Selinger algorithm. This work provides theoretical insight into why reinforcement learning may be successfully used to find optimally short gate sequences in quantum programming.
All-analog photoelectronic chip for high-speed vision tasks
Authors: Chen Yitong , Nazhamaiti Maimaiti , Xu Han , Meng Yao , Zhou Tiankuang , Li Guangpu , Fan Jingtao , Wei Qi , Wu Jiamin , Qiao Fei , Fang Lu , Dai Qionghai
Published: October 2023

Photonic computing enables faster and more energy-efficient processing of vision data1–5. However, experimental superiority of deployable systems remains a challenge because of complicated optical nonlinearities, considerable power consumption of analog-to-digital converters (ADCs) for downstream digital processing and vulnerability to noises and system errors1,6–8. Here we propose an all-analog chip combining electronic and light computing (ACCEL). It has a systemic energy efficiency of 74.8 peta-operations per second per watt and a computing speed of 4.6 peta-operations per second (more than 99% implemented by optics), corresponding to more than three and one order of magnitude higher than state-of-the-art computing processors, respectively. After applying diffractive optical computing as an optical encoder for feature extraction, the light-induced photocurrents are directly used for further calculation in an integrated analog computing chip without the requirement of analog-to-digital converters, leading to a low computing latency of 72 ns for each frame. With joint optimizations of optoelectronic computing and adaptive training, ACCEL achieves competitive classification accuracies of 85.5%, 82.0% and 92.6%, respectively, for Fashion-MNIST, 3-class ImageNet classification and time-lapse video recognition task experimentally, while showing superior system robustness in low-light conditions (0.14 fJ μm−2 each frame). ACCEL can be used across a broad range of applications such as wearable devices, autonomous driving and industrial inspections.
Evidence for a liquid silicate layer atop the Martian core
Authors: Khan A. , Huang D. , Durán C. , Sossi P. A. , Giardini D. , Murakami M.
Published: October 2023

Seismic recordings made during the InSight mission1 suggested that Mars’s liquid core would need to be approximately 27% lighter than pure liquid iron2,3, implying a considerable complement of light elements. Core compositions based on seismic and bulk geophysical constraints, however, require larger quantities of the volatile elements hydrogen, carbon and sulfur than those that were cosmochemically available in the likely building blocks of Mars4. Here we show that multiply diffracted P waves along a stratified core–mantle boundary region of Mars in combination with first-principles computations of the thermoelastic properties of liquid iron-rich alloys3 require the presence of a fully molten silicate layer overlying a smaller, denser liquid core. Inverting differential body wave travel time data with particular sensitivity to the core–mantle boundary region suggests a decreased core radius of 1,675 ± 30 km associated with an increased density of 6.65 ± 0.1 g cm−3, relative to previous models2,4–8, while the thickness and density of the molten silicate layer are 150 ± 15 km and 4.05 ± 0.05 g cm−3, respectively. The core properties inferred here reconcile bulk geophysical and cosmochemical requirements, consistent with a core containing 85–91 wt% iron–nickel and 9–15 wt% light elements, chiefly sulfur, carbon, oxygen and hydrogen. The chemical characteristics of a molten silicate layer above the core may be revealed by products of Martian magmatism.
A single photoreceptor splits perception and entrainment by cotransmission
Authors: Xiao Na , Xu Shuang , Li Ze-Kai , Tang Min , Mao Renbo , Yang Tian , Ma Si-Xing , Wang Peng-Hao , Li Meng-Tong , Sunilkumar Ajay , Rouyer François , Cao Li-Hui , Luo Dong-Gen
Published: October 2023

Vision enables both image-forming perception, driven by a contrast-based pathway, and unconscious non-image-forming circadian photoentrainment, driven by an irradiance-based pathway1,2. Although two distinct photoreceptor populations are specialized for each visual task3–6, image-forming photoreceptors can additionally contribute to photoentrainment of the circadian clock in different species7–15. However, it is unknown how the image-forming photoreceptor pathway can functionally implement the segregation of irradiance signals required for circadian photoentrainment from contrast signals required for image perception. Here we report that the Drosophila R8 photoreceptor separates image-forming and irradiance signals by co-transmitting two neurotransmitters, histamine and acetylcholine. This segregation is further established postsynaptically by histamine-receptor-expressing unicolumnar retinotopic neurons and acetylcholine-receptor-expressing multicolumnar integration neurons. The acetylcholine transmission from R8 photoreceptors is sustained by an autocrine negative feedback of the cotransmitted histamine during the light phase of light–dark cycles. At the behavioural level, elimination of histamine and acetylcholine transmission impairs R8-driven motion detection and circadian photoentrainment, respectively. Thus, a single type of photoreceptor can achieve the dichotomy of visual perception and circadian photoentrainment as early as the first visual synapses, revealing a simple yet robust mechanism to segregate and translate distinct sensory features into different animal behaviours.
Land cover and forest health indicator datasets for central India using very-high resolution satellite data
Authors: Khanwilkar Sarika , Galletti Chris , Mondal Pinki , Urpelainen Johannes , Nagendra Harini , Jhala Yadvendradev , Qureshi Qamar , DeFries Ruth
Published: October 2023

Satellite imagery has been used to provide global and regional estimates of forest cover. Despite increased availability and accessibility of satellite data, approaches for detecting forest degradation have been limited. We produce a very-high resolution 3-meter (m) land cover dataset and develop a normalized index, the Bare Ground Index (BGI), to detect and map exposed bare ground within forests at 90 m resolution in central India. Tree cover and bare ground was identified from Planet Labs Very High-Resolution satellite data using a Random Forest classifier, resulting in a thematic land cover map with 83.00% overall accuracy (95% confidence interval: 61.25%–90.29%). The BGI is a ratio of bare ground to tree cover and was derived by aggregating the land cover. Results from field data indicate that the BGI serves as a proxy for intensity of forest use although open areas occur naturally. The BGI is an indicator of forest health and a baseline to monitor future changes to a tropical dry forest landscape at an unprecedented spatial scale.
Chromosome-scale assembly of the wild wheat relative Aegilops umbellulata
Authors: Abrouk Michael , Wang Yajun , Cavalet-Giorsa Emile , Troukhan Maxim , Kravchuk Maksym , Krattinger Simon G.
Published: October 2023

Wild wheat relatives have been explored in plant breeding to increase the genetic diversity of bread wheat, one of the most important food crops. Aegilops umbellulata is a diploid U genome-containing grass species that serves as a genetic reservoir for wheat improvement. In this study, we report the construction of a chromosome-scale reference assembly of Ae. umbellulata accession TA1851 based on corrected PacBio HiFi reads and chromosome conformation capture. The total assembly size was 4.25 Gb with a contig N50 of 17.7 Mb. In total, 36,268 gene models were predicted. We benchmarked the performance of hifiasm and LJA, two of the most widely used assemblers using standard and corrected HiFi reads, revealing a positive effect of corrected input reads. Comparative genome analysis confirmed substantial chromosome rearrangements in Ae. umbellulata compared to bread wheat. In summary, the Ae. umbellulata assembly provides a resource for comparative genomics in Triticeae and for the discovery of agriculturally important genes.
Pair barracuda swarm optimization algorithm: a natural-inspired metaheuristic method for high dimensional optimization problems
Authors: Guo Jia , Zhou Guoyuan , Yan Ke , Sato Yuji , Di Yi
Published: October 2023

High-dimensional optimization presents a novel challenge within the realm of intelligent computing, necessitating innovative approaches. When tackling high-dimensional spaces, traditional evolutionary tools often encounter pitfalls, including dimensional catastrophes and a propensity to become trapped in local optima, ultimately compromising result accuracy. To address this issue, we introduce the Pair Barracuda Swarm Optimization (PBSO) algorithm in this paper. PBSO employs a unique strategy for constructing barracuda pairs, effectively mitigating the challenges posed by high dimensionality. Furthermore, we enhance global search capabilities by incorporating a support barracuda alongside the leading barracuda pair. To assess the algorithm’s performance, we conduct experiments utilizing the CEC2017 standard function and compare PBSO against five state-of-the-art natural-inspired optimizers in the control group. Across 29 test functions, PBSO consistently secures top rankings with 9 first-place, 13 second-place, 5 third-place, 1 fourth-place, and 1 fifth-place finishes, yielding an average rank of 2.0345. These empirical findings affirm that PBSO stands as the superior choice among all test algorithms, offering a dependable solution for high-dimensional optimization challenges.
KDM5 family of demethylases promotes CD44-mediated chemoresistance in pancreatic adenocarcinomas
Authors: Wang Dan , Zhang Yingjun , Liao Zhouning , Ge Heming , Güngör Cenap , Li Yuqiang
Published: October 2023

A growing body of evidence suggests that the histone demethylase-lysine demethylase 5 (KDM5) family is associated with drug resistance in cancer cells. However, it is still not clear whether KDM5 family members promote chemotherapy resistance in pancreatic ductal adenocarcinomas (PDAC). Comprehensive bioinformatics analysis was performed to investigate the prognostic value, and functional mechanisms of KDM5 family members in PDAC. The effects of KDM5 family members on drug resistance in PDAC cells and the relationship with CD44, as a stem cell marker, were explored by gene knockout and overexpression strategies. Finally, our findings were validated by functional experiments such as cell viability, colony formation and invasion assays. We found that the expression of KDM5A/C was significantly higher in gemcitabine-resistant cells than in sensitive cells, consistent with the analysis of the GSCALite database. The knockdown of KDM5A/C in PDAC cells resulted in diminished drug resistance, less cell colonies and reduced invasiveness, while KDM5A/C overexpression showed the opposite effect. Of note, the expression of KDM5A/C changed accordingly with the knockdown of CD44. In addition, members of the KDM5 family function in a variety of oncogenic pathways, including PI3K/AKT and Epithelial-Mesenchymal Transition. In conclusion, KDM5 family members play an important role in drug resistance and may serve as new biomarkers or potential therapeutic targets in PDAC patients.
Real-time driver monitoring system with facial landmark-based eye closure detection and head pose recognition
Authors: Kim Dohun , Park Hyukjin , Kim Tonghyun , Kim Wonjong , Paik Joonki
Published: October 2023

This paper introduces a real-time Driver Monitoring System (DMS) designed to monitor driver behavior while driving, employing facial landmark estimation-based behavior recognition. The system utilizes an infrared (IR) camera to capture and analyze video data. Through facial landmark estimation, crucial information about the driver’s head posture and eye area is extracted from the detected facial region, obtained via face detection. The proposed method consists of two distinct modules, each focused on recognizing specific behaviors. The first module employs head pose analysis to detect instances of inattention. By monitoring the driver’s head movements along the horizontal and vertical axes, this module assesses the driver’s attention level. The second module implements an eye-closure recognition filter to identify instances of drowsiness. Depending on the continuity of eye closures, the system categorizes them as either occasional drowsiness or sustained drowsiness. The advantages of the proposed method lie in its efficiency and real-time capabilities, as it solely relies on IR camera video for computation and analysis. To assess its performance, the system underwent evaluation using IR-Datasets, demonstrating its effectiveness in monitoring and recognizing driver behavior accurately. The presented real-time Driver Monitoring System with facial landmark-based behavior recognition offers a practical and robust approach to enhance driver safety and alertness during their journeys.
SLC7A11, a potential immunotherapeutic target in lung adenocarcinoma
Authors: Shan Qingqing , Zhang Chi , Li Yangke , Li Qunying , Zhang Yifan , Li Xue , Shi Junqing , Hu Fengying
Published: October 2023

SLC7A11 has significant translational value in cancer treatment. However, there are few studies on whether SLC7A11 affects the immune status of lung adenocarcinoma (LUAD). Information on SLC7A11 expression and its impact on prognosis was obtained from the cancer genome atlas and gene expression omnibus databases. The differentially expressed genes (DEGs) were analysed by GO and KEGG. GSEA enrichment analysis was performed in the SLC7A11-high and SLC7A11-low groups. The relationship between SLC7A11 and tumour immunity, immune checkpoints, and immune cell infiltration was studied using R language. We analysed the correlation between SLC7A11 and chemotactic factors (CFs) and chemokine receptors using the TISIDB database. SLC7A11 is overexpressed in many tumours, including LUAD. The 5-year overall survival of patients in the SLC7A11-high group was lower than in the SLC7A11-low group. KEGG analysis found that the DEGs were enriched in ferroptosis signaling pathways. GSEA analysis found that the survival-related signaling pathways were enriched in the SLC7A11-low group. The SLC7A11-low group had higher immune scores and immune checkpoint expression. SLC7A11 was negatively correlated with many immune cells (CD8+ T cells, immature dendritic cells), CFs, chemokine receptors (such as CCL17/19/22/23, CXCL9/10/11/14, CCR4/6, CX3CR1, CXCR3) and MHCs (major histocompatibility complex). SLC7A11 may regulate tumour immunity and could be a potential therapeutic target for LUAD.