bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimizing solar energy efficiency with an improved hill-climbing maximum power point tracking control approach: hardware implementation
Authors: El Alami Yassine , Chetouani Elmostafa , Mokhliss Hamza , Ouerradi Fatima , Aoutoul Mohssin , Bounouar Said , Bendaoud Rachid , Faize Ahmed , Rmaily Redouane
Published: August 2024

This article implements maximum power point tracking (MPPT) based on the improved hill-climbing algorithm for photovoltaic (PV) systems feeding resistive loads. A direct current-to-direct current boost converter is inserted between the PV system and the load to achieve matching. The converter is managed using MPPT based on the hill-climbing algorithm. The objective of this paper is to optimize the code program to achieve the best compromise between accuracy and rapidity by implementing this algorithm using a microcontroller. Two PV systems are tested under identical meteorological conditions. In the first, an improved hill-climbing MPPT controller is used whereas, in the second, the conventional version is employed. The experimental results obtained show a significant enhancement in terms of speed for the improved algorithm with a value of 0.4 s for the response time and 3% for the oscillation power; those values remain satisfactory in terms of precision of the algorithm compared with the conventional system studied and the compared algorithm from the literature.
Morphological effect of TiO2 nanoparticles in TiO2/g-C3N4 heterojunctions on photocatalytic dye degradation
Authors: Deng Zijian , Osuga Ryota , Matsubara Masaki , Kanie Kiyoshi , Muramatsu Atsushi
Published: August 2024

The effects of TiO2 nanoparticle (NP) morphology on the photocatalytic activity of physically assembled TiO2 NP/g-C3N4 heterojunctions (TCNPHY) were investigated. Spherical, spindle, and cubic TiO2 NPs were synthesized and separately supported on g-C3N4 nanosheets to form physically assembled TCNPHY catalysts. The photocatalytic activity for methylene blue degradation observed for TCNPHY with the cubic TiO2 NPs supported higher light absorption and a lower recombination rate; therefore, this was an adequate catalyst for the construction of catalytically active heterojunctions. The cubic TiO2 TCNPHY exhibited a degradation rate that was 2.2 times higher than that for the g-C3N4 nanosheets alone.
Endoscopic submucosal dissection for superficial esophageal cancer in the remnant esophagus after esophagectomy
Authors: Suzuki Yugo , Kikuchi Daisuke , Nakamura Satoshi , Iizuka Toshiro , Ochiai Yorinari , Hayasaka Junnosuke , Ueno Masaki , Udagawa Harushi , Hoteya Shu
Published: August 2024

Treatment of esophageal cancer in the remnant esophagus after esophagectomy is highly invasive, therefore, early detection and minimally invasive treatment are considered necessary. Consequently, we aimed to clarify the safety and efficacy of endoscopic submucosal dissection (ESD) for residual esophageal cancer compared to that for esophageal cancer in a normal cervical esophagus. This study involved 47 patients with 59 residual esophageal cancers and 92 patients with 107 cervical esophageal cancers in normal esophagus who underwent ESD between January 2008 and December 2023. Their clinicopathological findings and long-term outcomes were retrospectively collected and evaluated. The median tumor diameter was 13 mm, and the median procedure time was 31 minutes in remnant esophagus group, with no significant difference between the two groups. No serious complications such as perforation, massive intraoperative bleeding, and pneumonia were observed in the remnant group, except for one case of postoperative bleeding. The rates of complete resection and disease specific survival were not significantly different between two groups, with complete resection rate of 86.4% and 5-year disease-specific survival rate of 95.7% in the remnant esophagus group. No local recurrence was observed during the median observation period of 43 months in the remnant esophagus group. ESD for superficial cancer of the remnant esophagus showed a high complete resection rate without serious complications and good local-regional control with no evidence of local recurrence. This indicates that ESD is a safe and useful treatment for superficial cancer of the remnant esophagus.
Sex-related differences in the clinical course of aortic root and ascending aortic aneurysms: the DisSEXion Study
Authors: Notenboom Maximiliaan L , de Keijzer Adine R , Veen Kevin M , Gökalp Arjen , Bogers Ad J J C , Heijmen Robin H , van Kimmenade Roland R J , Geuzebroek Guillaume S C , Mokhles M Mostafa , Bekkers Jos A , Roos-Hesselink Jolien W , Takkenberg Johanna J M
Published: August 2024

Background and Aims

To explore male–female differences in aneurysm growth and clinical outcomes in a two-centre retrospective Dutch cohort study of adult patients with ascending aortic aneurysm (AscAA).

Methods

Adult patients in whom imaging of an AscAA (root and/or ascending: ≥40 mm) was performed between 2007 and 2022 were included. Aneurysm growth was analysed using repeated measurements at the sinuses of Valsalva (SoV) and tubular ascending aorta. Male–female differences were explored in presentation, aneurysm characteristics, treatment strategy, survival, and clinical outcomes.

Results

One thousand eight hundred and fifty-eight patients were included (31.6% female). Median age at diagnosis was 65.4 years (interquartile range: 53.4–71.7) for females and 59.0 years (interquartile range: 49.3–68.0) for males (P < .001). At diagnosis, females more often had tubular ascending aortic involvement (75.5% vs. 70.2%; P = .030) while males more often had SoV involvement (42.8% vs. 21.6%; P < .001). Maximum absolute aortic diameter, at any location, at diagnosis did not differ between females (45.0 mm) and males (46.5 mm; P = .388). In females, tubular ascending growth was faster (P < .001), whereas in males, SoV growth was faster (P = .005), corrected for covariates. Unadjusted 10-year survival was 72.5% [95% confidence interval (CI) 67.8%–77.6%] for females and 78.3% (95% CI 75.3%–81.3%) for males (P = .010). Twenty-three type A dissections occurred, with an incidence rate of 8.2/1000 patient-years (95% CI 4.4–14.1) in females and 2.4/1000 patient-years (95% CI 1.2–4.5) in males [incidence rate ratio females/males: 3.4 (95% CI 1.5–8.0; P = .004)].

Conclusions

In patients having entered a diagnostic programme, involvement of aortic segments and age- and segment-related growth patterns differ between women and men with AscAA, particularly at an older age. Unravelling of these intertwined observations will provide a deeper understanding of AscAA progression and outcome in women and men and can be used as an evidence base for patient-tailored clinical guideline development.
Nationwide analysis of the relationship between low ambient temperature and acute aortic dissection-related hospitalizations
Authors: Kato Katsuhito , Nishino Takuya , Otsuka Toshiaki , Seino Yoshihiko , Kawada Tomoyuki
Published: August 2024

Aims

Acute aortic dissection (AAD) is a life-threatening cardiovascular emergency. Therefore, identifying modifiable risk factors for AAD is of great public health significance. An association between ambient temperature (AT) and AAD has been reported; however, not all findings have been elucidated. This study examined the association between AAD-related hospitalization and AT using data from the Japanese Registry of All Cardiac and Vascular Diseases Diagnostic Procedure Combination (JROAD-DPC), which is a nationwide claims-based database.

Methods and results

This nationwide time-stratified case-crossover study evaluated data of hospitalized patients with AAD from 1119 certified hospitals between 2012 and 2020 using the JROAD-DPC database. Conditional logistic regression and distributed lag non-linear models were used to investigate the association between average daily temperature and AAD-related hospitalization. Among the 96 812 cases analysed, the exposure–response curve between AT and AAD-related hospitalization showed an increase in the odds ratio for lower temperatures, with a peak at time −10°C (odds ratio: 2.28, 95% confidence interval: 1.92–2.71, compared with that at 20°C). The effects of temperature on lag days 0 and 1 were also significant.

Stratified analyses showed a greater association between AT and AAD-related hospitalization for the following variables: older age (≥75 years), female sex (44.4%, the mean age ± SD was 76 ± 12 years), low body mass index (<22), winter season, and warmer regions.

Conclusion

Low AT is associated with an increased risk of AAD-related hospitalization. Several susceptible groups are affected by cold temperatures and have a higher risk of hospitalization.
Mutations in nuclear genes encoding mitochondrial ribosome proteins restore pollen fertility in S male-sterile maize
Authors: Wang Yan , Williams-Carrier Rosalind , Meeley Robert , Fox Timothy , Chamusco Karen , Nashed Mina , Hannah L Curtis , Gabay-Laughnan Susan , Barkan Alice , Chase Christine
Published: August 2024

The interaction of plant mitochondrial and nuclear genetic systems is exemplified by mitochondria-encoded cytoplasmic male sterility (CMS) under the control of nuclear restorer-of-fertility genes. The S type of CMS in maize is characterized by a pollen collapse phenotype and a unique paradigm for fertility restoration in which numerous nuclear restorer-of-fertility lethal mutations rescue pollen function but condition homozygous-lethal seed phenotypes. Two nonallelic restorer mutations recovered from Mutator transposon-active lines were investigated to determine the mechanisms of pollen fertility restoration and seed lethality. Mu Illumina sequencing of transposon-flanking regions identified insertion alleles of nuclear genes encoding mitochondrial ribosomal proteins RPL6 and RPL14 as candidate restorer-of-fertility lethal mutations. Both candidates were associated with lowered abundance of mitochondria-encoded proteins in developing maize pollen, and the rpl14 mutant candidate was confirmed by independent insertion alleles. While the restored pollen functioned despite reduced accumulation of mitochondrial respiratory proteins, normal-cytoplasm plants heterozygous for the mutant alleles showed a significant pollen transmission bias in favor of the nonmutant Rpl6 and Rpl14 alleles. CMS-S fertility restoration affords a unique forward genetic approach to investigate the mitochondrial requirements for, and contributions to, pollen and seed development.
SKN-1 activation during infection of Caenorhabditis elegans requires CDC-48 and endoplasmic reticulum proteostasis
Authors: Gabaldón Carolaing , Karakuzu Ozgur , Garsin Danielle A
Published: August 2024

During challenge of Caenorhabditis elegans with human bacterial pathogens such as Pseudomonas aeruginosa and Enterococcus faecalis, the elicited host response can be damaging if not properly controlled. The activation of Nrf (nuclear factor erythroid-related factor)/CNC (Cap-n-collar) transcriptional regulators modulates the response by upregulating genes that neutralize damaging molecules and promote repair processes. Activation of the C. elegans Nrf ortholog, SKN-1, is tightly controlled by a myriad of regulatory mechanisms, but a central feature is an activating phosphorylation accomplished by the p38 mitogen-activated kinase (MAPK) cascade. In this work, loss of CDC-48, an AAA+ ATPase, was observed to severely compromise SKN-1 activation on pathogen and we sought to understand the mechanism. CDC-48 is part of the endoplasmic reticulum (ER)-associated degradation (ERAD) complex where it functions as a remodeling chaperone enabling the translocation of proteins from the ER to the cytoplasm for degradation by the proteosome. Interestingly, one of the proteins retrotranslocated by ERAD, a process necessary for its activation, is SKN-1A, the ER isoform of SKN-1. However, we discovered that SKN-1A is not activated by pathogen exposure in marked contrast to the cytoplasmic-associated isoform SKN-1C. Rather, loss of CDC-48 blocks the antioxidant response normally orchestrated by SKN-1C by strongly inducing the unfolded protein response (UPRER). The data are consistent with the model of these 2 pathways being mutually inhibitory and support the emerging paradigm in the field of coordinated cooperation between different stress responses.
Navigating a “Good Death” During COVID-19: Understanding Real-Time End-of-Life Care Structures, Processes, and Outcomes Through Clinical Notes
Authors: Franzosa Emily , Kim Patricia S , Moreines Laura T , McDonald Margaret V , David Daniel , Boafo Jonelle , Schulman-Green Dena , Brody Abraham A , Aldridge Melissa D
Published: August 2024

Background and Objectives

The coronavirus disease 2019 (COVID-19) pandemic severely disrupted hospice care, yet there is little research regarding how widespread disruptions affected clinician and family decision-making. We aimed to understand how the pandemic affected structures, processes, and outcomes of end-of-life care.

Research Design and Methods

Retrospective narrative chart review of electronic health records of 61 patients referred and admitted to hospice from 3 New York City geriatrics practices who died between March 1, 2020, and March 31, 2021. We linked longitudinal, unstructured medical, and hospice electronic health record notes to create a real-time, multiperspective trajectory of patients’ interactions with providers using directed content analysis.

Results

Most patients had dementia and were enrolled in hospice for 11 days. Care processes were shaped by structural factors (staffing, supplies, and governmental/institutional policies), and outcomes were prioritized by care teams and families (protecting safety, maintaining high-touch care, honoring patient values, and supporting patients emotionally and spiritually). Processes used to achieve these outcomes were decision-making, care delivery, supporting a “good death,” and emotional and spiritual support.

Discussion and Implications

Care processes were negotiated throughout the end of life, with clinicians and families making in-the-moment decisions. Some adaptations were effective but also placed extraordinary pressure on paid and family caregivers. Healthcare teams’ and families’ goals to meet patients’ end-of-life priorities can be supported by ongoing assessment of patient goals and process changes needed to support them, stronger structural supports for paid and family caregivers, incentivizing relationships across primary care and hospice teams, and extending social work and spiritual care.
How do free healthcare policies impact utilization of maternal and child health services in fragile settings? Evidence from a controlled interrupted time series analysis in Burkina Faso
Authors: Aye Thit Thit , Nguyen Hoa Thi , Petitfour Laurène , Ridde Valéry , Amberg Felix , Bonnet Emmanuel , Seynou Mariam , Kiendrébéogo Joël Arthur , De Allegri Manuela
Published: August 2024

Burkina Faso has implemented a nationwide free healthcare policy (gratuité) for pregnant and lactating women and children under 5 years since April 2016. Studies have shown that free healthcare policies can increase healthcare service use. However, the emerging coronavirus disease 2019 pandemic, escalating insecurity and the political situation in recent years might have affected the implementation of such policies. No studies have looked at whether the gratuité maintained high service use under such changing circumstances. Our study aimed to assess the effects of gratuité on the utilization of facility-based delivery and curative care of children under 5 years in light of this changing context. We employed a controlled interrupted time series analysis using data from the Health Management Information System and annual statistical reports of 2560 primary health facilities from January 2013 to December 2021. We focused on facility-based deliveries and curative care for children under 5 years, with antenatal care and curative care for children over 5 years as non-equivalent controls. We employed segmented regression with the generalized least square model, accounting for autocorrelation and monthly seasonality. The monthly utilization rate among children under 5 years compared to those above 5 years (controls) immediately increased by 111.19 visits per 1000 children (95% CI: 91.12, 131.26) due to the gratuité. This immediate effect declined afterwards with a monthly change of 0.93 per 1000 children (95% CI: −1.57, −0.29). We found no significant effects, both immediate and long-term, on the use of maternal care services attributable to the gratuité. Our findings suggest that free healthcare policies can be instrumental in improving healthcare, yet more comprehensive strategies are needed to maintain healthcare utilization. Our findings reflect the overall situation in the country, while localized research is needed to understand the effect of insecurity and the pandemic at the local level and the effects of gratuité across geographies and socioeconomic statuses.
Stakeholder perspectives on the governance and accountability of Nigeria’s Basic Health Care Provision Fund
Authors: Adeoye Mary I , Obi Felix A , Adrion Emily R
Published: August 2024

In recent decades, Nigeria has implemented a number of health financing reforms, yet progress towards Universal Health Coverage (UHC) has remained slow. In particular, the introduction of the Basic Health Care Provision Fund (BHCPF) through the National Health Act of 2014 sought to increase coverage of basic health services in Nigeria. However, recent studies have shown that health financing schemes like the BHCPF in Nigeria are suboptimal and have frequently attributed this to weak accountability and governance of the schemes. However, little is known about the accountability and governance of health financing in Nigeria, particularly from the perspective of key actors within the system. This study explores perceptions around governance and accountability through qualitative in-depth interviews with key BHCPF actors, including high-level government officers, academics and Civil Society Organizations. Thematic analysis of the findings reveals broad views among respondents that financial processes are appropriately ring-fenced, and that financial mismanagement is not the most pressing accountability gap. Importantly, respondents report that accountability processes are unclear and weak in subnational service delivery, and cite low utilization, implicit priority setting and poor quality as issues. To accelerate UHC progress, the accountability framework must be redesigned to include greater strategic participation and leadership from subnational governments.
A ‘natcon takeover’? The New Right and the future of American foreign policy
Authors: Borg Stefan
Published: August 2024

Donald Trump's capture of the Republican Party enabled a radical questioning of received wisdom within the broader conservative intellectual movement. In particular, it enabled the emergence of a post-Trump, distinctly American New Right. This policy paper examines the American New Right and its visions for United States foreign policy. In the context of contemporary American politics, the New Right is best understood as a rejection of the ‘fusionism’ that has characterized US conservatism since the early decades after the Second World War. The paper argues that there are three major identifiable parts of the New Right: the Claremonters, the post-liberals and the national conservatives. In part because of their ‘big-tent’ character, as well as deft intellectual leadership by Yoram Hazony, the national conservatives have become the most influential group within the contemporary New Right. The article also examines how the New Right has attempted to create an alternative ideational infrastructure, with a clear focus on entrenching itself through large-scale credentialing of personnel deemed to be loyal to the New Right's agenda. There is reason to speak of a ‘natcon takeover’ of traditional conservative institutions. This is particularly the case with the Heritage Foundation, the largest and most influential conservative think tank. While all segments of the New Right ostensibly embrace some notion of grand strategic restraint, the policy paper argues that the rise of national conservatism is likely to accelerate the US pivot from Europe to Asia rather than lead to neo-isolationism, as is sometimes suggested.
Advancements in nuclear imaging using radiolabeled nanobody tracers to support cancer immunotherapy
Authors: Zeven Katty , Lauwers Yoline , De Mey Lynn , Debacker Jens M , De Pauw Tessa , De Groof Timo W M , Devoogdt Nick
Published: August 2024

The evolving landscape of cancer immunotherapy has revolutionized cancer treatment. However, the dynamic tumor microenvironment has led to variable clinical outcomes, indicating a need for predictive biomarkers. Noninvasive nuclear imaging, using radiolabeled modalities, has aided in patient selection and monitoring of their treatment response. This approach holds promise for improving diagnostic accuracy, providing a more personalized treatment regimen, and enhancing the clinical response. Nanobodies or single-domain antibodies, derived from camelid heavy-chain antibodies, allow early timepoint detection of targets with high target-to-background ratios. To date, a plethora of nanobodies have been developed for nuclear imaging of tumor-specific antigens, immune checkpoints, and immune cells, both at a preclinical and clinical level. This review comprehensively outlines the recent advancements in nanobody-based nuclear imaging, both on preclinical and clinical levels. Additionally, the impact and expected future advancements on the use of nanobody-based radiopharmaceuticals in supporting cancer diagnosis and treatment follow-up are discussed.
Bacterial Genomics for National Antimicrobial Resistance Surveillance in Cambodia
Authors: Yek Christina , Lon Chanthap , Chea Sophana , Lay Sreyngim , Oum Meng Heng , Tang Gechlang , Lon Chansothea , Pacheco Andrea R , Drobish Ian , Stuehser Reagan , Ly Sokna , Sath Ratanak , Srouen Malin , Bin Chamrouen , Chak Chanthou , Seang Sosorphea , Srey Viso , Chhor Bunna , Nhem Somary , Chiek Sivhour , Dork Rina , Dekker John P , Seng Heng , Krang Sidonn , Ly Sovann , Manning Jessica E
Published: August 2024

Background

Antimicrobial resistance (AMR) surveillance in low- and middle-income countries (LMICs) often relies on poorly resourced laboratory processes. Centralized sequencing was combined with cloud-based, open-source bioinformatics solutions for national AMR surveillance in Cambodia.

Methods

Blood cultures growing gram-negative bacteria were collected at 6 Cambodian hospitals (January 2021 to October 2022). Isolates were obtained from pure plate growth and shotgun DNA sequencing performed in country. Using public nucleotide and protein databases, reads were aligned for pathogen identification and AMR gene characterization. Multilocus sequence typing was performed on whole-genome assemblies and haplotype clusters compared against published genomes.

Results

Genes associated with acquired resistance to fluoroquinolones were identified in 59%, trimethoprim/sulfamethoxazole in 45%, and aminoglycosides in 52% of 715 isolates. Extended-spectrum β-lactamase encoding genes were identified in 34% isolates, most commonly blaCTX-M-15, blaCTX-M-27, and blaCTX-M-55 in Escherichia coli sequence types 131 and 1193. Carbapenemase genes were identified in 12% isolates, most commonly blaOXA-23, blaNDM-1, blaOXA-58, and blaOXA-66 in Acinetobacter species. Phylogenetic analysis revealed clonal strains of Acinetobacter baumannii, representing suspected nosocomial outbreaks, and genetic clusters of quinolone-resistant typhoidal Salmonella and extended-spectrum β-lactamase E. coli cases suggesting community transmission.

Conclusions

With accessible sequencing platforms and bioinformatics solutions, bacterial genomics can supplement AMR surveillance in LMICs.
Visualizing multilayer spatiotemporal epidemiological data with animated geocircles
Authors: Ondov Brian , Patel Harsh B , Kuo Ai-Te , Kastner John , Han Yunheng , Wei Hong , Elmqvist Niklas , Samet Hanan
Published: August 2024

Objective

The COVID-19 pandemic emphasized the value of geospatial visual analytics for both epidemiologists and the general public. However, systems struggled to encode temporal and geospatial trends of multiple, potentially interacting variables, such as active cases, deaths, and vaccinations. We sought to ask (1) how epidemiologists interact with visual analytics tools, (2) how multiple, time-varying, geospatial variables can be conveyed in a unified view, and (3) how complex spatiotemporal encodings affect utility for both experts and non-experts.

Materials and Methods

We propose encoding variables with animated, concentric, hollow circles, allowing multiple variables via color encoding and avoiding occlusion problems, and we implement this method in a browser-based tool called CoronaViz. We conduct task-based evaluations with non-experts, as well as in-depth interviews and observational sessions with epidemiologists, covering a range of tools and encodings.

Results

Sessions with epidemiologists confirmed the importance of multivariate, spatiotemporal queries and the utility of CoronaViz for answering them, while providing direction for future development. Non-experts tasked with performing spatiotemporal queries unanimously preferred animation to multi-view dashboards.

Discussion

We find that conveying complex, multivariate data necessarily involves trade-offs. Yet, our studies suggest the importance of complementary visualization strategies, with our animated multivariate spatiotemporal encoding filling important needs for exploration and presentation.

Conclusion

CoronaViz’s unique ability to convey multiple, time-varying, geospatial variables makes it both a valuable addition to interactive COVID-19 dashboards and a platform for empowering experts and the public during future disease outbreaks. CoronaViz is open-source and a live instance is freely hosted at http://coronaviz.umiacs.io.
Reproductive parameters of a new biocontrol agent, Eupeodes americanus (Diptera: Syrphidae) and comparison with the commercialized Aphidoletes aphidimyza (Diptera: Cecidomyiidae)
Authors: Ouattara Téné Yacine , Fournier Marc , Gonzalez Noémie , Rojo Santos , Lucas Eric
Published: August 2024

The American hoverfly Eupeodes americanus (Wiedemann) (Diptera: Syrphidae) is an aphidophagous predator during its larval stage and is currently being evaluated for inclusion in biocontrol programs as a new biocontrol agent. However, little is known about its reproductive aptitudes. The objective of the present study was to determine the reproductive parameters of E. americanus and to compare them with those of a commercialized and widely used biological control agent for aphids, the aphid midge Aphidoletes aphidimyza (Rondani) (Diptera: Cecidomyiidae). The preoviposition period, oviposition period, adult longevity, lifetime and daily fecundity, egg hatching rate, and fertility were determined for E. americanus females and compared to those of A. aphidimyza. Trials were conducted under laboratory conditions in rearing cages on the broad bean plant Vicia faba L. (Fabaceae), infested with pea aphids Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae). The results revealed that the preoviposition period, oviposition period, and adult longevity were significantly longer in E. americanus than in A. aphidimyza. The daily fecundity and egg-hatching rate were similar in both species. However, lifetime fecundity and fertility were considerably higher in E. americanus than in A. aphidimyza. This study demonstrates that the reproductive capacity of E. americanus is clearly superior to that of A. aphidimyza and therefore supports its inclusion in the aphid pest management program as a new biocontrol agent.
SPC squatting
Authors: Stief Marco
Published: August 2024

Supplementary protection certificates (SPCs) for pharmaceutical products are an important complement to patent protection which is often inadequate in commercial terms. SPCs are designed to ensure that originators can amortize their high investments in research and clinical trials. But unlike in the USA, for example, the European SPC is not simply a patent term extension. Rather, it is a unique form of intellectual property right whose subject matter is not the overall patented invention, but the active ingredient or combination of active ingredients of a patented and authorized pharmaceutical product. This link between the basic patent and market authorization has led to many questions of interpretation and Court of Justice of the European Union (CJEU) rulings since the SPC Regulation was adopted. An issue that has not yet been decided by the CJEU concerns the discrepancy between the ownership of the patent and the marketing authorisation under pharmaceutical law. This scenario, in which a patent proprietor relies on the marketing authorisation of a third party (possibly even a competitor) in said patent proprietor’s application for an SPC, is also referred to as “SPC squatting”. The following article discusses the admissibility of such a practice de lege lata, which also becomes relevant in light of current reform efforts by the legislator.
Deubiquitinase BAP1 is crucial for surface expression of T cell receptor (TCR) complex, T cell-B cell conjugate formation, and T cell activation
Authors: Radhakrishnan Dhwani , Kotulová Jana , Hofmanová Lucie , Sithara Anjana Anilkumar , Turi Marcello , Žihala David , Ďurech Michal , Vrána Jan , Uleri Valeria , Niederlova Veronika , Stepanek Ondrej , Chyra Zuzana , Jelínek Tomáš , Hájek Roman , Hrdinka Matouš
Published: August 2024

The adaptive immune response critically hinges on the functionality of T cell receptors, governed by complex molecular mechanisms, including ubiquitination. In this study, we delved into the role of in T cell immunity, focusing on T cell–B cell conjugate formation and T cell activation. Using a CRISPR-Cas9 screening approach targeting deubiquitinases genes in Jurkat T cells, we identified BAP1 as a key positive regulator of T cell-B cell conjugate formation. Subsequent investigations into BAP1 knockout cells revealed impaired T cell activation, evidenced by decreased MAPK and NF-kB signaling pathways and reduced CD69 expression upon T cell receptor stimulation. Flow cytometry and qPCR analyses demonstrated that BAP1 deficiency leads to decreased surface expression of T cell receptor complex components and reduced mRNA levels of the co-stimulatory molecule CD28. Notably, the observed phenotypes associated with BAP1 knockout are specific to T cells and fully dependent on BAP1 catalytic activity. In-depth RNA-seq and mass spectrometry analyses further revealed that BAP1 deficiency induces broad mRNA and protein expression changes. Overall, our findings elucidate the vital role of BAP1 in T cell biology, especially in T cell-B cell conjugate formation and T cell activation, offering new insights and directions for future research in immune regulation.
Commercial products are not effective at repelling European deer keds, Lipoptena cervi (Diptera: Hippoboscidae) but may increase mortality after exposure
Authors: Skvarla Michael J , Poh Karen , Norman Calvin , Machtinger Erika T
Published: August 2024

European deer keds, Lipoptena cervi (Linnaeus, 1758), are hematophagous ectoparasitic flies known to bite cervids and noncervids, including humans. To prevent deer keds from landing and biting hosts, 5 commercially available insect repellents (DEET, IR3535, oil of lemon eucalyptus (OLE), picaridin, and permethrin) and water control were evaluated to determine repellency efficacy and postexposure mortality of deer keds. While there was a significant difference between the groups tested, a post hoc analysis revealed that no treatment was significantly different from the water control. Deer ked survival was different amongst the treatments, with deer keds exposed to permethrin dying much sooner than those exposed to other treatments or control (median survival for permethrin = 0.58 h). Post-hoc pairwise comparisons revealed that deer keds exposed to DEET or IR3535 had similar survival rates (4.82 and 5.15 h, respectively). Still, there were significantly lower survival times for DEET compared to OLE (6.33 h) and picaridin (15.00 h). Deer keds exposed to the water control survived the longest (23.12 h). Overall, deer ked repellency was not significantly different from the control, but permethrin-treated clothes can effectively kill deer keds in a short amount of time, thereby protecting those who recreate outdoors or encounter animals carrying deer keds.
Disability, Offense, and the Expressivist Objection to Medical Aid in Dying
Authors: Kious Brent M
Published: August 2024

One criticism of medical aid in dying (MAID) is the expressivist objection: MAID is morally wrong because it expresses judgments about disabilities or persons with disabilities, that are offensive, disrespectful, or discriminatory. The expressivist objection can be made at the level of individual patients, medical providers, or the state. The expressivist objection originated with selective abortion, and responses to it in that context typically claim either that selective abortion does not express specific judgments about disabilities, or that any judgments expressed are not offensive. This response is inadequate: MAID often does express negative judgments about disabilities, which could reasonably be seen as offensive. But, does this offensiveness make MAID wrong? Drawing on Joel Feinberg’s account of offense, I argue that it is unlikely that the offensiveness of the judgments expressed by individuals who seek MAID or through the state’s legalization of MAID is enough to make it morally impermissible.
Climate warming advances plant reproductive phenology in China’s northern grasslands
Authors: Bai Lu , Tian Lei , Ren Zhiguo , Song Xiaohui , Yu Kailiang , Meng Lin , Hou Zhanfeng , Ren Haiyan
Published: August 2024

Despite much recent progress, our understanding of plant phenology response to climate change remains incomplete. In particular, how and to what extent climate warming affects the vegetative and reproductive phenology of different plant functional groups in northern grassland ecosystems remains largely unexplored. Here, we compiled data of 1758 observations from 25 individual studies and carried out a meta-analysis of plant phenology in relation to temperature changes across a range of plant species and functional groups in northern China. We show that climate warming tended to extend the duration of reproductive phenology while having no effect on the duration of vegetative phenology. We also identified specific temperature sensitivities for different phenological stages: 1.73 days °C−1 for budding, −3.38 days °C−1 for leaf spreading and 0.56 days °C−1 for yellow withered stage, respectively. Notably, warming resulted in earlier leaf spreading in shrubs and semi-shrubs, but caused a delay in the budding time of sedges. In terms of reproductive phenology, temperature sensitivity was −1.73 days °C−1 for flowering time, −2.53 days °C−1 for fruit ripening and −0.11 days °C−1 for fruit shedding, respectively. Warming advanced the flowering and fruit repining time of all functional groups except for legumes. Our results indicate that elevated temperatures advanced reproductive phenology and extended its duration in northern grasslands, while showing no impact on vegetative phenology. Our findings demonstrate the differential responses of different functional groups to warming, highlighting the diverse growth strategies and adaptation of grassland plants in a warming world.
The Kumbh Mela religious mass gathering in India: reducing risks for crowd-surge associated deaths and crush injuries
Authors: Sharma Avinash , McCloskey Brian , Parker Salim , Shafi Shuja , Azhar Esam I , Memish Ziad A , Zumla Alimuddin
Published: August 2024

Deaths and injuries due to crowd surges are increasingly reported from mass gathering events worldwide. The 2025 Kumbh Mela religious pilgrimage is expected to attract ~100 million pilgrims from across India, Asia and other continents. Reducing the risk of crowd surges at the Kumbh Mela remains a crucial public health preparedness priority.
International Energy Investment Law
Authors: Cameron Peter
Published: August 2024

The focus of this book is the law on international investment relating to the energy sector, and particularly the guarantees it offers investors for making long-term commitments. Through a study of energy contracts and investment treaties, the book asks whether the law is successful in delivering the kind of long-term stability for the business environment that energy investors typically seek, and further, what limits there may be on those guarantees and why. A subordinate question the book addresses is whether there are distinct features of the legal protection of international investments in the energy sector that justify the use of the term ‘international energy investment law’.
Energy Investment Law
Authors: Cameron Peter
Published: August 2024

This chapter explains that investments in various kinds of energy comprise a higher proportion of total international investment than any other sector of the global economy. It discusses the strategic sensitivity of energy investments to nation-states that has guaranteed a strong state interest and established sound legal arrangements among states to support certain transactions and the resolution of differences. It also clarifies how states take responsibility for the allocation of rights to investors and regulate the resulting activities, even often participating in them to some degree. The chapter describes energy investments as usually international, large-scale, and longer in duration than most types of investments. It highlights the legal framework for energy investment that comprises the large number of international investment treaties or agreements (IIAs), including the multilateral Energy Charter Treaty (ECT).
The Classic Tests of Contract-Based Stability
Authors: Cameron Peter
Published: August 2024

This chapter traces robust conflicts in the history of international energy investment between host governments in countries with energy resources or energy networks and foreign companies that are invited in to develop resources or networks under long-term contracts. It cites conflicts that emerged between investors and states with respect to the generation, transmission and sale of electricity and gas, and with respect to investments in various forms of renewable energy. It also talks about conflicts in the development of oil and gas resources, which were evident in Latin America and the Middle East as early as the 1930s. The chapter examines the arbitral awards made in the 1970s and early 1980s that followed the wave of unilateral state actions at the time. It discusses the 'classic tests' of the validity, scope, and function of contractual stabilization in international energy arrangements.
Latin America
Authors: Cameron Peter
Published: August 2024

This chapter details the government policies that initiated coordinated swings toward and then sharply away from foreign investment in Latin America. It cites the international investment treaty regime and investor-state arbitration that have been challenged and sometimes rejected by several states of the region. It also refers to regional or domestic forums for dispute settlement that have been championed as an alternative and more appropriate venue for dispute settlement. The chapter emphasizes how the Latin American region provides a case study of challenges to various kinds of stability guarantees and give important examples of awards in proceedings that have arisen from state actions to comprehensively revise arrangements with investors in energy projects. It looks at investments in the energy sector have that figured prominently in disputes between foreign investors and host states.
Principles of the Digital Services Act
Authors: Husovec Martin
Published: August 2024

Numerous questions were at the heart of the parliamentary discussions over the provisions of the Digital Services Act (DSA), the EU’s new regulatory framework for digital services. How should liberal democracies prevent illegal and harmful online activities and protect fundamental rights? How should digital service providers assess the impact of their technology on others? And how should technology companies moderate user-generated content? Principles of the Digital Services Act analyses the DSA’s key provisions, dissecting its mechanisms and components, to understand the new law’s likely impact on digital services in Europe and beyond. The book puts the new legal framework into its political, economic, and social contexts by explaining its grounding within the frameworks of economic regulation and human rights. It examines the European legislature’s approach to the DSA, offering a detailed historical account of the legislative and pre-legislative process. The book argues that the envisaged regulatory system has the potential to boost trust in the digital environment. However, its mechanisms must be able to rely on the robust network of civil society organisations, and the regulators should follow a set of principles. In this way, the DSA’s goal can be achieved through means that are firmly aligned with respect for individual liberties, including the freedom of expression. Combining academic research with practical insights, Principles of the Digital Services Act offers a robust analysis of how to apply and further develop the most important tools of the DSA, to rebuild trust in the digital environment.
Injunctions and Orders
Authors: Husovec Martin
Published: August 2024

The chapter describes the special place of injunctive relief and other types of orders under the European Union system of liability exemptions for third-party content. It explains why such orders are exempted from the liability framework if they are issued by authorities and do not amount to general monitoring. The text is accompanied by several examples of specific orders that have been litigated in the past two decades. Finally, the reader learns about the shortcomings of the latest case law trying to limit the permissible scope of such injunctions and how the provisions on orders in the Digital Services Act affect the pre-existing framework.
Risk-Based Approach to Digital Services
Authors: Husovec Martin
Published: August 2024

The chapter describes why digital services had to become regulated like many other industries and whether the risk-based approach is appropriate. After concluding that the approach is justified for several reasons, such as information asymmetry and fast innovation cycles, the chapter looks at the key characteristics of digital services and compares them with some of the often-used examples from other industries, such as banking or food safety. It concludes that while parallels are useful, the communication tools cannot be regulated in the same way, and the regulators should not rely on the precautionary principle as they do in other areas. Instead, the regulators must remain deferential to legislatures about what content is prohibited or allowed. This limited risk management approach, it is argued, is to be preferred to full risk management, which does not shy away from changing the underlying content rules.
Transparency
Authors: Husovec Martin
Published: August 2024

The chapter maps the various transparency obligations advanced by the Digital Services Act. First, the chapter describes access to data held by very large online platforms and very large search engines and conceptualises this access in light of the DSA’s regulatory goals. It is argued that data access is among the most important tools envisaged by the whole regulation because it allows researchers to set the enforcement agenda for Big Tech and the European Commission. Second, the chapter looks at the transparency reports that apply to the various tiers of services to map the content moderation efforts of platforms, such as the takedown or appeal rates, and resources used to tackle the challenges.
The DSA as a Cornerstone of the EU Single Market
Authors: Husovec Martin
Published: August 2024

The chapter describes the role of national rulemaking before the adoption of the Digital Services Act and after it. Under the E-Commerce Directive, the country-of-origin principle, and various notification mechanisms increasingly constrained the national law-making. Post-DSA, it is argued, the new harmonised rules offer very little space for national legislatures to introduce new domestic regulations. The only exceptions are the rules about illegal content, super-users, and orders that can be issued by domestic authorities or courts. Many other rules, especially those concerning due diligence in the DSA’s scope, will be pre-empted and thus inapplicable. Therefore, the Member States are likely to focus their attention on initiatives at the European level and push for more detailed Codes of Conduct.
The DSA as a Mixed Enforcement System
Authors: Husovec Martin
Published: August 2024

The chapter describes the public and private enforcement mechanisms of the Digital Services Act (DSA). Public enforcement mechanisms are at the heart of the legislative text. The DSA’s provisions mostly rely on administrative enforcement by the European Commission and the Digital Service Coordinators. Despite this, it is argued that private enforcement is not pre-empted and remains crucial. Private enforcement is argued to have a lot of potential to improve public participation and increase enforcement efforts in the Member States. Among private enforcement tools, the place of collective redress exercised by consumer organisations is considered to be key. Thus, it is argued that the system of the DSA should be better described as a mixed enforcement system that is not entirely reliant on administrative authorities.
Due Process and Transparency Requirements for Investigating Competition Cases in Taiwan
Authors: Chen Andy C M
Published: August 2024

This chapter uses the enforcement experience of Taiwan to illustrate how due process and transparency requirements are implemented in competition. Part I introduces the regulatory framework for due process and transparency requirements in Taiwan. Part II describes how these requirements are implemented during investigation procedures for competition cases. Part III highlights the problems associated with implementation in practice. Part IV examines the likely causes for these problems and offers preliminary thoughts on how these problems should be addressed, and Part V concludes. As a mature jurisdiction of competition law in Asia, the fundamental principles and rules honoured by other experienced jurisdictions in this regard have already been in existence in both the general legislations on administrative investigations and sanctions, as well as in the specific competition legislations in Taiwan. However, the implementation of these provisions can be limited by the provisos that authorize the Taiwan Fair Trade Commission the discretion to deny due process or transparency requests from investigated parties.
Procedural Fairness in Japan
Authors: Shiraishi Tadashi
Published: August 2024

In Japan, debates on procedural fairness have been closely connected to administrative fines, which were first introduced to the Antimonopoly Act by the 1977 Amendment. This chapter first examines the 1977, 2005, 2009, and 2013 Amendments. A weak administrative fine system was introduced in 1977, strengthened in 2005 and 2009, and repercussions appeared in 2013. Then, the competition authority regained power in the debates on procedural fairness after the 2013 Amendment. The chapter also mentions the commitment decision procedure from the perspective of administrative fines. It is shown that administrative fines have almost always controlled and directed the debates on procedural fairness. As of August 2017, the results of the current endeavours by the Japan Fair Trade Commission remain to be seen.