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This study examines the relationship between climate change and happiness using panel data from 140 countries between 2008 and 2020. We investigate whether greenhouse gas (GHG) emissions—specifically carbon dioxide (CO₂), methane (CH₄), and nitrous oxide (N₂O)—influence subjective well-being, while controlling for socio-economic factors such as GDP per capita, child mortality, and inequality. The analysis reveals that while emissions have limited direct effects on happiness, economic development and public health remain critical drivers of well-being. Notably, developed countries show a negative association between emissions and happiness, highlighting growing environmental concerns, whereas economic growth plays a dominant role in shaping happiness in developing countries. Robustness checks, including two-stage least squares (2SLS) regression and panel-corrected standard errors (PCSE), confirm the stability of the findings. These results suggest that climate policies should align with economic and social priorities to enhance well-being. We recommend adopting context-specific strategies—such as sustainable development and adaptation measures—that account for regional differences in environmental impacts. This study contributes to the growing literature on the climate-happiness nexus and provides valuable insights for policymakers striving to balance climate action with societal well-being.

Initiated by the Chinese president Xi Jinping in 2013, the Belt and Road initiative (BRI) is a multi-trillion-dollar agenda for facilitating trade and investment, especially massive infrastructural developments. In recent years, discussions around the BRI have been increasing as more than 130 countries and 30 international organizations have officially joined the initiative [1], collaborating in a series of transnational infrastructure projects funded by Chinese companies or the Chinese state. This dataset provides 500,711 posts and 714,794 reposting threads related to the BRI on Twitter. The dataset was collected through the Twitter API by applying a set of keywords: “belt and road”, “one belt one road”, “new silk road”, “maritime silk road”, and “silk road economic belt”, which included the words and their hashtag forms to download the raw data from Twitter. The time series of the dataset is from 7 September 2013 to 30 November 2021. Furthermore, the dataset is annotated in terms of languages, emotional polarity, geopolitical entities, and credibility by employing textual analytics in language detection, neural machine translation, and lexicon-based sentiment analysis. To facilitate future research, we classified the dataset into three databases that can be analyzed separately and reused in research related to various fields, such as political science, network science, and sociology to study public opinions about the BRI and their dissemination patterns.

Pharmaceutical manufacturing is reliant upon bioprocessing approaches to generate the range of therapeutic products that are available today. The high cost of production, susceptibility to process failure, and requirement to achieve consistent, high-quality product means that process monitoring is paramount during manufacturing. Process analytic technologies (PAT) are key to ensuring high quality product is produced at all stages of development. Spectroscopy-based technologies are well suited as PAT approaches as they are non-destructive and require minimum sample preparation. This study explored the use of a novel attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy platform, which utilises disposable internal reflection elements (IREs), as a method of upstream bioprocess monitoring. The platform was used to characterise organism health and to quantify cellular metabolites in growth media using quantification models to predict glucose and lactic acid levels both singularly and combined. Separation of the healthy and nutrient deficient cells within PC space was clearly apparent, indicating this technique could be used to characterise these classes. For the metabolite quantification, the binary models yielded R2 values of 0.969 for glucose, 0.976 for lactic acid. When quantifying the metabolites in tandem using a multi-output partial least squares model, the corresponding R2 value was 0.980. This initial study highlights the suitability of the platform for bioprocess monitoring and paves the way for future in-line developments.

Abstract The advances in cancer research achieved in the last 50 years have been remarkable and have provided a deeper knowledge of this disease in many of its conceptual and biochemical aspects. From viewing a tumor as a ‘simple’ aggregate of mutant cells and focusing on detecting key cell changes leading to the tumorigenesis, the understanding of cancer has broadened to consider it as a complex organ interacting with its close and far surroundings through tumor and non-tumor cells, metabolic mechanisms, and immune processes. Metabolism and the immune system have been linked to tumorigenesis and malignancy progression along with cancer-specific genetic mutations. However, most technologies developed to overcome the barriers to earlier detection are focused solely on genetic information. The concept of cancer as a complex organ has led to research on other analytical techniques, with the quest of finding a more sensitive and cost-effective comprehensive approach. Furthermore, artificial intelligence has gained broader consensus in the oncology community as a powerful tool with the potential to revolutionize cancer diagnosis for physicians. We herein explore the relevance of the concept of cancer as a complex organ interacting with the bodily surroundings, and focus on promising emerging technologies seeking to diagnose cancer earlier, such as liquid biopsies. We highlight the importance of a comprehensive approach to encompass all the tumor and non-tumor derived information salient to earlier cancer detection.

Abstract Background Mucopolysaccharidosis IIIC (MPSIIIC) is one of four Sanfilippo diseases sharing clinical symptoms of severe cognitive decline and shortened lifespan. The missing enzyme, heparan sulfate acetyl-CoA: α-glucosaminide-N-acetyltransferase (HGSNAT), is bound to the lysosomal membrane, therefore cannot cross the blood-brain barrier or diffuse between cells. We previously demonstrated disease correction in MPSIIIC mice using an Adeno-Associated Vector (AAV) delivering HGSNAT via intraparenchymal brain injections using an AAV2 derived AAV-truetype (AAV-TT) serotype with improved distribution over AAV9. Methods Here, intraparenchymal AAV was delivered in sheep using catheters or Hamilton syringes, placed using Brainlab cranial navigation for convection enhanced delivery, to reduce proximal vector expression and improve spread. Results Hamilton syringes gave improved AAV-GFP distribution, despite lower vector doses and titres. AAV-TT-GFP displayed moderately better transduction compared to AAV9-GFP but both serotypes almost exclusively transduced neurons. Functional HGSNAT enzyme was detected in 24-37% of a 140g gyrencephalic sheep brain using AAV9-HGSNAT with three injections in one hemisphere. Conclusions Despite variabilities in volume and titre, catheter design may be critical for efficient brain delivery. These data help inform a clinical trial for MPSIIIC.

Mutations in the CLN5 gene cause the fatal, pediatric, neurodegenerative disease CLN5 neuronal ceroid lipofuscinosis. Affected children suffer progressive neuronal loss, visual failure and premature death. Presently there is no treatment. This study evaluated dual intracerebroventricular (ICV) and intravitreal (IVT) administration of a self-complementary adeno-associated viral vector encoding ovine CLN5 (scAAV9/oCLN5) into CLN5 affected sheep (CLN5−/−) at various disease stages. CLN5 disease progression was slowed in pre-symptomatic sheep who received a moderate dose of scAAV9/oCLN5, whilst a higher ICV dose treatment in early and advanced symptomatic animals delayed or halted disease progression. Intracranial (brain) volume loss was attenuated in all treatment cohorts, and visual function was also sustained in both the early and advanced symptomatic treated sheep over the 24-month duration of the study. Robust CLN5 protein expression was detected throughout the brain and spinal cord, and improvements in central nervous system and retinal disease correlates were observed. These findings hold translational promise for extending and improving the quality of life in both pre-symptomatic and symptomatic CLN5 patients, and prompted the initiation of the first in-human Phase I/II clinical trial testing ICV/IVT administration of scAAV9 encoding human CLN5 (https://clinicaltrials.gov/; NCT05228145).

Abstract Cancer is a worldwide pandemic. The burden it imposes grows steadily on a global scale causing emotional, physical, and financial strains on individuals, families, and health care systems. Despite being the second leading cause of death worldwide, many cancers do not have screening programs and many people with a high risk of developing cancer fail to follow the advised medical screening regime due to the nature of the available screening tests and other challenges with compliance. Moreover, many liquid biopsy strategies being developed for early detection of cancer lack the sensitivity required to detect early-stage cancers. Early detection is key for improved quality of life, survival, and to reduce the financial burden of cancer treatments which are greater at later stage detection. This review examines the current liquid biopsy market, focusing in particular on the strengths and drawbacks of techniques in achieving early cancer detection. We explore the clinical utility of liquid biopsy technologies for the earlier detection of solid cancers, with a focus on how a combination of various spectroscopic and -omic methodologies may pave the way for more efficient cancer diagnostics.

CLN5 neuronal ceroid lipofuscinosis (NCL, Batten disease) is a rare, inherited fatal neurodegenerative disorder caused by mutations in the CLN5 gene. The disease is characterised by progressive neuronal loss, blindness, and premature death. There is no cure. This study evaluated the efficacy of intracerebroventricular (ICV) delivery of an adeno-associated viral vector encoding ovine CLN5 (scAAV9/oCLN5) in a naturally occurring sheep model of CLN5 disease. CLN5 affected (CLN5−/−) sheep received low, moderate, or high doses of scAAV9/oCLN5 at three disease stages. The treatment delayed disease progression, extended survival and slowed stereotypical brain atrophy in most animals. Of note, one high dose treated animal only developed mild disease symptomology and survived to 60.1 months of age, triple the natural life expectancy of an untreated CLN5−/− sheep. Eyesight was not preserved at any administration age or dosage. Histopathologic examination revealed that greater transduction efficiency was achieved through higher ICV doses, and this resulted in greater amelioration of disease pathology. Together with other pre-clinical data from CLN5−/− sheep, the safety and efficacy data from these investigational new drug (IND)-enabling studies supported the initiation of the first in-human CLN5 gene therapy clinical study using the ICV delivery route for the treatment of CLN5 NCL.Clinical Trial Registration:https://clinicaltrials.gov/, identifier NCT05228145

We report the results of an extensive set of simulations exploring the sensitivity of the BlackCAT CubeSat to long-duration gamma-ray bursts (GRBs). BlackCAT is a NASA APRA-funded CubeSat mission for the detection and real-time subarcminute localization of high-redshift ( z ≳ 3.5) GRBs. Thanks to their luminous and long-lived afterglow emissions, GRBs are uniquely valuable probes of high-redshift star-forming galaxies and the intergalactic medium. In addition, each detected GRB with a known redshift serves to localize a region of high-redshift star formation in three dimensions, enabling deep follow-on searches for host galaxies and associated local and large-scale structures. We explore two distinct models for the GRB redshift distribution and luminosity function, both consistent with Swift observations. We find that, for either model, BlackCAT is expected to detect a mean of 42 bursts per year on orbit, with 6.7% to 10% of these at z > 3.5. BlackCAT bursts will be localized to an r _90 ≲ 55″ precision and reported to the community within seconds. Due to the mission orbit and pointing scheme, bursts will be located in the night sky and well placed for deep multiwavelength follow-up observations. BlackCAT is on schedule to achieve launch readiness in 2025.

We report the discovery of the unusually bright long-duration gamma-ray burst (GRB), GRB 221009A, as observed by the Neil Gehrels Swift Observatory (Swift), Monitor of All-sky X-ray Image, and Neutron Star Interior Composition Explorer Mission. This energetic GRB was located relatively nearby ( z = 0.151), allowing for sustained observations of the afterglow. The large X-ray luminosity and low Galactic latitude ( b = 4.°3) make GRB 221009A a powerful probe of dust in the Milky Way. Using echo tomography, we map the line-of-sight dust distribution and find evidence for significant column densities at large distances (≳10 kpc). We present analysis of the light curves and spectra at X-ray and UV–optical wavelengths, and find that the X-ray afterglow of GRB 221009A is more than an order of magnitude brighter at T _0 + 4.5 ks than that from any previous GRB observed by Swift. In its rest frame, GRB 221009A is at the high end of the afterglow luminosity distribution, but not uniquely so. In a simulation of randomly generated bursts, only 1 in 10 ^4 long GRBs were as energetic as GRB 221009A; such a large E _γ _,iso implies a narrow jet structure, but the afterglow light curve is inconsistent with simple top-hat jet models. Using the sample of Swift GRBs with redshifts, we estimate that GRBs as energetic and nearby as GRB 221009A occur at a rate of ≲1 per 1000 yr—making this a truly remarkable opportunity unlikely to be repeated in our lifetime.

Soil nutrient supply is one of several environmental and biotic drivers of planted forest productivity and testing the soil and tree foliage can inform nutrient management decisions. For many forest companies and research organisations the collection and analysis of a large number of soil samples for chemical properties has previously been considered expensive if not cost-prohibitive. Consequently, site nutrition status may not be measured or, as is the case with many forestry managers, efforts are directed towards foliar sampling to assess tree health and vigour. Diffuse reflectance infrared spectroscopy has emerged as a quick, cost-effective, and non-destructive method for the analysis of many soil properties. Because of the advances in diffuse reflectance spectroscopy, we see potential advantages to the forest industry and research organisations by utilising this method as a cost-effective means of analysing forest soil and foliage nutrient status. In this study we build a New Zealand planted-forest specific mid-infrared spectral training library for soil and foliage chemical properties. Nationally applicable partial least squares regression models for soil and foliage chemical properties were built from the respective libraries and were applied to an independent national data set to test their robustness. The soil properties with good (R2 >0.8) and fair (R2 0.5–0.8) predictions on the independent data set were soil pH, total carbon, total nitrogen, total phosphorus, available aluminium, available calcium, CEC (cation exchange capacity), base saturation, and the following elemental totals: aluminium, calcium, iron, potassium, magnesium, nickel, and zinc. The foliage properties with fair predictions (R2 0.5–0.8) were total calcium, total potassium and total phosphorus. Total nitrogen had an R2 of 0.47 which was a result of a narrow range in nitrogen values within the test set. The root mean squared error (RMSE) for foliage nitrogen was acceptable. Most of the key planted forest soil and tree foliage nutrient properties were able to be predicted using MIR (mid infrared) spectroscopy. However, some soil available macro-nutrients and all measured soil available micro-nutrients and foliage micro-nutrients predictions were unreliable (R2

The neuronal ceroid lipofuscinoses (NCLs; Batten disease) are fatal, mainly childhood, inherited neurodegenerative lysosomal storage diseases. Sheep affected with a CLN6 form display progressive regionally defined glial activation and subsequent neurodegeneration, indicating that neuroinflammation may be causative of pathogenesis. In this study, aggregation chimeras were generated from homozygous unaffected normal and CLN6 affected sheep embryos, resulting in seven chimeric animals with varied proportions of normal to affected cells. These sheep were classified as affected-like, recovering-like or normal-like, based on their cell-genotype ratios and their clinical and neuropathological profiles. Neuropathological examination of the affected-like animals revealed intense glial activation, prominent storage body accumulation and severe neurodegeneration within all cortical brain regions, along with vision loss and decreasing intracranial volumes and cortical thicknesses consistent with ovine CLN6 disease. In contrast, intercellular communication affecting pathology was evident at both the gross and histological level in the normal-like and recovering-like chimeras, resulting in a lack of glial activation and rare storage body accumulation in only a few cells. Initial intracranial volumes of the recovering-like chimeras were below normal but progressively recovered to about normal by two years of age. All had normal cortical thicknesses, and none went blind. Extended neurogenesis was evident in the brains of all the chimeras. This study indicates that although CLN6 is a membrane bound protein, the consequent defect is not cell intrinsic. The lack of glial activation and inflammatory responses in the normal-like and recovering-like chimeras indicate that newly generated cells are borne into a microenvironment conducive to maturation and survival.

The Bahá’í Faith is an important case for a discussion on dignity, religion and human rights. Beyond the notions of dignity enshrined in its basic teachings, a core concern of the Bahá’í community is how to build dignity into the pattern of social relations of an emerging global civilization. The oneness of humanity is the core principle around which all Bahá’í teachings revolve, and within this principle is enshrined not only the inherent, God-given nobility and dignity of every individual but also the responsibility of creating new patterns of social relations, forms of community, processes of education, and structures of institutional authority that consciously strive to create a global polity that protects and affirms the dignity of all humans, in all of their diversity. In this paper, we examine the foundations of human dignity in the Bahá’í Faith in four parts. First, we explore the use of the term “dignity” in Bahá’í sacred texts and its relationship to the concepts of “nobility" and “rights”. Second, we examine how Bahá’ís seek to put into practice their conception of dignity through a democratic system of global governance, grounded in processes of consultative deliberation, referred to as the Bahá’í Administrative Order. Third, we highlight how the Bahá’í community is seeking to cultivate conditions of dignity in its current educational endeavours, which seeks to contribute to the betterment of local communities throughout the world. Fourth, we explore the ongoing and centuries-long persecution of the Bahá’ís in Iran to understand the implications of dignity in responding to oppression.

The HR 2562 system is a rare case where a brown dwarf companion resides in a cleared inner hole of a debris disk, offering invaluable opportunities to study the dynamical interaction between a substellar companion and a dusty disk. We present the first ALMA observation of the system as well as the continued Gemini Planet Imager monitoring of the companion’s orbit with six new epochs from 2016 to 2018. We update the orbital fit, and in combination with absolute astrometry from GAIA, place a 3 σ upper limit of 18.5 M _J on the companion’s mass. To interpret the ALMA observations, we used radiative transfer modeling to determine the disk properties. We find that the disk is well resolved and nearly edge-on. While the misalignment angle between the disk and the orbit is weakly constrained, due to the short orbital arc available, the data strongly support a (near) coplanar geometry for the system. Furthermore, we find that the models that describe the ALMA data best have inner radii that are close to the companion’s semimajor axis. Including a posteriori knowledge of the system’s SED further narrows the constraints on the disk’s inner radius and places it at a location that is in reasonable agreement with (possibly interior to) predictions from existing dynamical models of disk truncation by an interior substellar companion. HR 2562 has the potential over the next few years to become a new test bed for dynamical interaction between a debris disk and a substellar companion.

We report the radio and high-energy properties of a new outburst from the radio-loud magnetar 1E 1547.0−5408. Following the detection of a short burst from the source with Swift-BAT on 2022 April 7, observations by NICER detected an increased flux peaking at (6.0 ± 0.4) × 10 ^−11 erg s ^−1 cm ^−2 in the soft X-ray band, falling to a baseline level of 1.7 × 10 ^−11 erg s ^−1 cm ^−2 over a 17 day period. Joint spectroscopic measurements by NICER and NuSTAR indicated no change in the hard nonthermal tail despite the prominent increase in soft X-rays. Observations at radio wavelengths with Murriyang, the 64 m Parkes radio telescope, revealed that the persistent radio emission from the magnetar disappeared at least 22 days prior to the initial Swift-BAT detection and was redetected two weeks later. Such behavior is unprecedented in a radio-loud magnetar, and may point to an unnoticed slow rise in the high-energy activity prior to the detected short bursts. Finally, our combined radio and X-ray timing revealed the outburst coincided with a spin-up glitch, where the spin frequency and spin-down rate increased by 0.2 ± 0.1 μ Hz and (−2.4 ± 0.1) × 10 ^−12 s ^−2 , respectively. A linear increase in the spin-down rate of (−2.0 ± 0.1) × 10 ^−19 s ^−3 was also observed over 147 days of postoutburst timing. Our results suggest that the outburst may have been associated with a reconfiguration of the quasi-polar field lines, likely signaling a changing twist, accompanied by spatially broader heating of the surface and a brief quenching of the radio signal, yet without any measurable impact on the hard X-ray properties.

Issue: The impact of neurological disorders is recognised globally, with one in six people affected in their lifetime and few treatments to slow or halt disease progression. This is due in part to the increasing ageing population, and is confounded by the high failure rate of translation from rodent-derived therapeutics to clinically effective human neurological interventions. Improved translation is demonstrated using higher order mammals with more complex/comparable neuroanatomy. These animals effectually span this translational disparity and increase confidence in factors including routes of administration/dosing and ability to scale, such that potential therapeutics will have successful outcomes when moving to patients. Coupled with advancements in genetic engineering to produce genetically tailored models, livestock are increasingly being used to bridge this translational gap. Approach: In order to aid in standardising characterisation of such models, we provide comprehensive neurological assessment protocols designed to inform on neuroanatomical dysfunction and/or lesion(s) for large animal species. We also describe the applicability of these exams in different large animals to help provide a better understanding of the practicalities of cross species neurological disease modelling. Recommendation: We would encourage the use of these assessments as a reference framework to help standardise neurological clinical scoring of large animal models.