bluuebunny/crossref_metadata_2025 huggingface dataset:
Trained Judgment and Appreciation
Authors: Kennedy Meegan
Published: December 2024

Victorian microscopists used skeptical tropes to define the educated judgment that encourages accurate rather than speculative or hasty interpretations. Microscopy poses uniquely difficult interpretive challenges, from the mental gyrations of optical sectioning involved in the discernment of structure, to the theoretical and practical discipline required to decipher the puzzling optical “ghosts” of diffraction. Like the physiological psychologists, Victorian microscopists debated how attention and automatic action (such as Carpenter’s concept of unconscious cerebration) affected observation and interpretation, and how training and habit might best aid their efforts to achieve an educated judgment. The trope of appreciation rewrites difficulty as achievement.
Minute Description
Authors: Kennedy Meegan
Published: December 2024

Although printed illustrations were increasingly available in Victorian scientific texts, microscopists developed skeptical textual strategies that enabled them to share the image textually for readers as well. Such written representations were valuable as reference objects and to instruct readers in microscopical practice. Authors use diverse forms of minute description, with varying relation to the exhaustive approach of mechanical objectivity, in an attempt to capture the microscopical image, archive it, and share it with others to experience virtually and later reproduce. Schacht sought to standardize detailed note-taking as a form of inductive reasoning; Beale urged observers to select only the most pertinent details of observation and leave room for doubt, to benefit the microscopical community. Minute description is anything but static; it collates an accumulated set of observations or reproduces a dynamic, developing image emerging from a mobile attention and a varied process of observation.
Value and Circumstance
Authors: Macklem Timothy
Published: December 2024

Four values—justice, consent, equality, and collective decision in the form of law—have profoundly shaped the practice of law in the twentieth century and beyond. Value and Circumstance revisits these political and moral ideals, uncovering the relationship between value and the moment. Each of the four key subjects is explored by returning to first principles in a way that invites reflection on the nature and functions of morality itself. The author claims that there is a deep and ongoing connection (and sometimes a dialogue) between the ideal and the everyday. As such, each of those things can be fully understood, appreciated, and pursued only in partnership with the other, even in cases when that partnership is unspoken and unacknowledged. Moreover, the book argues that sound moral comprehension is immanent in experience and engagement. We learn fully what justice calls for by doing justice; learn consent properly through practising consent; learn just when, in what manner, and in what domains to pursue equality through engaging with the prevailing equalities (both secured and unsecured) of our particular times and places; and learn what law should look like only by deciding what law is to be. In this dynamic, the moral world is steadily enlarged by our ordinary engagement with it. We both construct and draw upon the realm of value, to which we are accountable for our flourishing. We cannot live well with reference to the ideal alone.
Afterword: A Philosopher’s Life and its Worth
Authors: Macklem Timothy
Published: December 2024

This chapter offers a brief tribute to the work of Joseph Raz, the purpose of which is to describe a distinctive sense of the value of research, in academic culture and beyond, of which this book seeks to be a manifestation. As I have put it elsewhere, at the end of a life we tend to think in terms of memorable achievements, of how large a mark a person has left upon the world. We tend to be impressed by prominent lives, lived at scale. Yet it is the things that are not noticed that truly shape the world, by quietly remaking its fabric in ways that are seldom recorded and very often aren’t remembered, things pursued steadily and wisely for their own small sake and all the better for that.
UFOs, UAPs, Aliens, and Extraterrestrials
Authors: Pasulka Diana Walsh
Published: December 2024

Unexplained phenomena seen in the sky are a source of impressions that range from fear, awe, inspiration, and wonder. They’ve inspired interpretations as varied as lost souls from purgatory, armor-like flying shields, to contemporary belief in extraterrestrials (aliens) and their spaceships (Unidentified Flying Objects [UFOs]). It has been argued that the belief in UFOs corresponds to the Cold War and Space Race era of US history (1945–1991), but a review of sources indicates that beliefs that other planets are populated by nonhuman intelligent beings are found in written sources of the Western tradition since ancient Greece and earlier as attested to by the oral traditions of many indigenous cultures. Beliefs that nonhuman intelligences populate other dimensions and establish communication with human beings is also found in ancient and contemporary religious and esoteric traditions. These testimonies form core tenets of various cosmologies that range from those found within Hopi culture, esoteric movements like Rosicrucianism, and modern religious movements such as The Nation of Islam. The contemporary belief in UFOs and aliens in the United States has taken on uniquely distinct characteristics. Mass media in the 20th century circulated tropes of the alien invasion to a global audience, while the beginning of the Space Race resulted in manufactured aerial objects in the skies like satellites and spacecraft debris. The UFO hoax emerged as an interpretive lens through which UFOs were staged as simultaneously objects of belief and disbelief, one consequence of which was to destabilize conventional systematic methods of research into the phenomena. These developments, combined with the revelation that the US Air Force actively managed the public perception of UFOs through programs like Project Blue Book, contributed to a modern narrative that UFOs exist and that some governments know this and are keeping this information from the public. Although most of the UFOs analyzed were found to be of terrestrial origin, some remain legitimately unknown. In June 2021, the US Office of the Director of National Intelligence released an unclassified report of its findings. The group charged with compiling the report changed the name of the phenomena from UFOs to UAPs (Unidentified Anomalous Phenomena) to account for vehicular presence through transmedia phenomena such as water, air, space, or other mediums. Revelations about classified studies provoked the modern Disclosure movement, the goal of which is to prompt the US government to release information about its research programs. With the US government declaring that it studies UFOs, academics have also begun the public study without fear of stigma, augmenting the already advanced study of the topic by a parallel research tradition that consists of researchers who have had to use clandestine means to study and publish their research due to the stigma and classification associated with the topic.
Projections of Climate Change in South America
Authors: Arias Paola A. , Rivera Juan A. , Vera Carolina
Published: December 2024

Weather and climate in South America are influenced by a large variety of processes, including land–atmosphere and ocean–atmosphere interactions, orographic effects, and land use distributions. In addition, human activities are inducing climate change in South America in several ways. The contribution of the Working Group I (WGI) to the Sixth Assessment Report (AR6) of the Intergovernmental Panel on Climate Change (IPCC) provides a comprehensive assessment of the scientific evidence published up to 2021, regarding the observed and projected climate changes in South America. An updated synthesis based on results from General Circulation Models (GCMs) of the main projections of climate change in South America published after the IPCC AR6 WGI shows that although GCMs have considerably improved their representation of different aspects of regional climate, they still exhibit systematic errors like the Double Intertropical Convergence Zone bias as well as dry and warm biases in the Amazon and the Andes, respectively. The number of published scientific studies for South America, focused on the physical aspects of regional climate change, has considerably increased since 2021. The most recent literature confirms many of the projections presented in the IPCC AR6 WGI but expands on projections for different aspects of the regional atmospheric circulation and compound extremes. Despite the increasing amount of peer-reviewed literature since 2021, it is important to highlight that projections of annual and seasonal precipitation in South America exhibit large spread and uncertainty. Therefore, the necessity of producing high-resolution projections in South America is key, as is the importance of applying fit-for-purpose analysis focused on the models with physically consistent simulations of regional climate. This could be helpful in the building of the assessment of the physical aspects of climate change in South America to be presented in the next IPCC Assessment Report (AR7).
Internationalization Activities in Chilean Universities
Authors: Véliz Daniela , Bernasconi Andrés , Guzmán Pamela , Berríos Paulina , Celis Sergio
Published: December 2024

Internationalization is a key component in career development and success in the academic world. In the case of Chile, academic work has become more professionalized in recent decades. On the one hand, there has been an increase in the number of full-time professors, which indicates a greater dedication to the academic profession. This reality coexists with the predominance of part-time jobs characteristic of universities in Latin America. Additionally, an uptick of internationalization is indicated by the slight increase in the number of international professors. The activities through which academics develop internationalization activities in Chile were investigated through the Chilean version of the international survey of the academic profession, Academic Profession in the Knowledge-Based Society, applied to academics in 11 Chilean universities (2018–2019), with roughly 1,200 complete responses obtained. The results of Chile are aligned with international trends for peripheral countries. Even when different internationalization activities are reported by academics, the general image that emerges is that of a lukewarm internationalization: while most of the faculty collaborate internationally in research, they lament the lack of adequate university support for these activities and, more generally, do not see the internationalization rhetoric of the universities supported by action. Faculty are undecided on whether their institutions provide opportunities or funding for faculty members to undertake research abroad, for visiting international students, for visiting international scholars and for the recruitment of faculty members from foreign countries. On the other hand, professors claim that they emphasize international perspectives or content in their courses, and that their research is international in scope or orientation; both of these trends represents forms of internationalization at home. All benefits usually associated with increased internationalization are confirmed by respondents, except increased mobility of faculty and increased brain gain.
Multiproduct Firms in International Trade
Authors: Irlacher Michael
Published: December 2024

Starting in the late 2000s, a growing body of theoretical and empirical research has highlighted the significant role of multiproduct firms (MPFs) in international trade. Evidence from transaction-level data across various countries has shown that international trade flows are predominantly controlled by a few large multiproduct exporters, a concentration that has increased over time. Motivated by this empirical evidence, theoretical research has explored how firms determine the range of products for their domestic and export markets. Varieties produced by MPFs may be linked on both the demand side and the supply side. Demand linkages, often referred to as the “cannibalization effect,” imply a reduction in sales of an existing product due to the introduction of a new product by the same company. Supply linkages may arise from shared inputs, economies of scale and scope, and related production processes across varieties within the firm. These effects are specific to MPFs, and studying them generates novel insights compared to conventional models with single-product producers. New modeling techniques on product asymmetries within firms allow researchers to examine the internal adjustments in response to external shocks such as trade liberalization. Asymmetries among products not only determine how individual varieties are affected by the opportunities and threats of globalization but also influence the range of countries to which they are exported. Research has shown that firms frequently adjust their product mix across export destinations based on trade costs and the degree of competition in each market. Newly available transaction data, containing information at the firm-product-destination level, has made it possible to test new predictions specific to MPFs. These insights contribute to the understanding of adjustment processes within firms and how individual firms’ decisions impact aggregate outcomes such as product variety and productivity.
Between the Emergency and the Everyday
Authors: Jania Alex
Published: December 2024

This article tells the history of Miyagi Prefecture’s tsunami memorial halls, built following the 1933 Shōwa-Sarniku earthquake and tsunami, to grapple with the challenges of using memorials and collective memory to build resilience to future and recurring threats. The article takes the halls themselves as its main protagonists, following their memorial life cycles from their early conception, to their first lives as tsunami memorial halls, to their varied second lives after being repurposed, and finally to their steady destruction. Using insights from environmental history, memory studies, and critical disaster studies, the piece argues that the rise and fall of the tsunami memorial halls resulted from the incommensurability of human and geological timescales. It shows how the memory of and resilience to long-term seismic threats, which the halls tried to promote, gave way to a focus on everyday concerns at the human scale. These everyday concerns, caused by long-standing socioeconomic struggles and exacerbated in wartime and postwar Japan, led communities to shift the kinds of resilience they pursued with the halls. The article presents the memorial halls as a cautionary tale for those who use memory as a tool of resilience, arguing memorials themselves need to be made resilient to changing social and environmental conditions over deep time scales.
Survey of anatomic and clinical pathology services and infrastructure in Nigeria
Authors: Tucci Jonathan , Jacobs Jeremy W , Ibrahim Zainab U , Yusuf Aminu A , Umar Ali Bala , Milner Danny A , Eichbaum Quentin
Published: December 2024

Objectives

The paucity of data regarding the availability and extent of diagnostic medical services across sub-Saharan Africa hinders appropriate allocation of resources to improve health care in these regions. We assessed anatomic pathology (AP) and clinical pathology (CP) services in Nigeria, one of the most populous and fastest-growing countries in the world.

Methods

Two individual surveys (AP focused and CP focused) were developed by subject matter experts and administered to individuals involved in pathology and laboratory medicine diagnostic services at hospitals and laboratories across Nigeria between June and August 2022 using the American Society for Clinical Pathology email listserv.

Results

A total of 75 responses (29 AP and 46 CP) were received from 48 unique laboratories. Twenty-four sites provided AP services and 35 provided CP services. Eleven respondents performed both AP and CP services. Among AP services, basic surgical and cytopathology capabilities were available at most sites; however, the availability of automated technologies (eg, automated sample processing and staining) was more variable. Advanced diagnostic techniques, (eg, immunohistochemistry, human papillomavirus testing, molecular diagnostics) were rarely performed. The most frequently available CP services included hematology, microbiology, and chemistry. Microbiology services appeared to be among the most robust laboratory medicine services, particularly parasitology and bacteriology testing. Similar to AP services, more advanced diagnostic assays, such as flow cytometry, cytogenetics, and molecular testing, were largely unavailable.

Conclusions

These findings augment earlier studies and identify gaps that should be prioritized from a policy perspective to improve medical services and the overall health care infrastructure in Nigeria.
On Legal Expertise
Authors: Jiménez Felipe
Published: December 2024

Legal experts can reliably ascertain which legal norms are valid, and therefore which legal propositions are true. Legal experts are in this position because they have a grasp of the deep cognitive structure of law: the habits, commitments, and values that characterize the practice of legal argument in a specific jurisdiction. Legal expertise, thus understood, determines the content of the law, which is therefore not reducible to an aggregation of authoritative legal texts. Because social facts about legal experts’ values and commitments can determine the content of the law, references to moral considerations and principles of justice as valid legal reasons, in legal argument, are not a problem for (at least some forms of) legal positivism. Legal expertise thus shows that non-positivists might be right about (as they would put it) the irreducibility of legal content to communicative content without being right about the claims that moral facts determine the content of the law or that the validity of legal norms turns on moral considerations. Legal expertise also plays an important causal role in legal decision-making and is not, as some of the literature on judicial decision-making might suggest, epiphenomenal. From a moral perspective, while the existence of a class of legal experts is not necessarily valuable, it does have certain benefits, particularly in conditions of moral disagreement.
Overcoming COVID-19 vaccine hesitancy: An investigation of the Foreign Language Effect
Authors: Schmid Monika S , Roehr-Brackin Karen
Published: December 2024

Vaccine hesitancy remains one of the greatest challenges for global health. Previous research has shown that the recruitment of rational processes is increased in hypothetical decision-making scenarios when the underpinning information is presented in a foreign language. We investigate whether vaccine campaigns could benefit from this Foreign Language Effect (FLE) in order to overcome vaccine hesitancy. We conceptually replicated a recent study on COVID-19 vaccine campaigns (Freeman et al. 2021) to assess whether information can more successfully reduce vaccine hesitancy when presented in a foreign language as well as how other factors, such as language proficiency, impact the FLE. Based on a survey of 436 participants, we conclude that there may be the potential to lower vaccine hesitancy among individuals with English as a foreign language by presenting information in English, rather than in their native language. Conversely, participants who are native speakers of English and negatively predisposed against the COVID-19 vaccine react more negatively to information they read in a foreign language compared to their native language.
Meta learning for mutant HLA class I epitope immunogenicity prediction to accelerate cancer clinical immunotherapy
Authors: Xu Long , Yang Qiang , Dong Weihe , Li Xiaokun , Wang Kuanquan , Dong Suyu , Zhang Xianyu , Yang Tiansong , Luo Gongning , Liao Xingyu , Gao Xin , Wang Guohua
Published: December 2024

Accurate prediction of binding between human leukocyte antigen (HLA) class I molecules and antigenic peptide segments is a challenging task and a key bottleneck in personalized immunotherapy for cancer. Although existing prediction tools have demonstrated significant results using established datasets, most can only predict the binding affinity of antigenic peptides to HLA and do not enable the immunogenic interpretation of new antigenic epitopes. This limitation results from the training data for the computational models relying heavily on a large amount of peptide-HLA (pHLA) eluting ligand data, in which most of the candidate epitopes lack immunogenicity. Here, we propose an adaptive immunogenicity prediction model, named MHLAPre, which is trained on the large-scale MS-derived HLA I eluted ligandome (mostly presented by epitopes) that are immunogenic. Allele-specific and pan-allelic prediction models are also provided for endogenous peptide presentation. Using a meta-learning strategy, MHLAPre rapidly assessed HLA class I peptide affinities across the whole pHLA pairs and accurately identified tumor-associated endogenous antigens. During the process of adaptive immune response of T-cells, pHLA-specific binding in the antigen presentation is only a pre-task for CD8+ T-cell recognition. The key factor in activating the immune response is the interaction between pHLA complexes and T-cell receptors (TCRs). Therefore, we performed transfer learning on the pHLA model using the pHLA-TCR dataset. In pHLA binding task, MHLAPre demonstrated significant improvement in identifying neoepitope immunogenicity compared with five state-of-the-art models, proving its effectiveness and robustness. After transfer learning of the pHLA-TCR data, MHLAPre also exhibited relatively superior performance in revealing the mechanism of immunotherapy. MHLAPre is a powerful tool to identify neoepitopes that can interact with TCR and induce immune responses. We believe that the proposed method will greatly contribute to clinical immunotherapy, such as anti-tumor immunity, tumor-specific T-cell engineering, and personalized tumor vaccine.
CancerHubs: a systematic data mining and elaboration approach for identifying novel cancer-related protein interaction hubs
Authors: Ferrari Ivan , De Grossi Federica , Lai Giancarlo , Oliveto Stefania , Deroma Giorgia , Biffo Stefano , Manfrini Nicola
Published: December 2024

Conventional approaches to predict protein involvement in cancer often rely on defining either aberrant mutations at the single-gene level or correlating/anti-correlating transcript levels with patient survival. These approaches are typically conducted independently and focus on one protein at a time, overlooking nucleotide substitutions outside of coding regions or mutational co-occurrences in genes within the same interaction network. Here, we present CancerHubs, a method that integrates unbiased mutational data, clinical outcome predictions and interactomics to define novel cancer-related protein hubs. Through this approach, we identified TGOLN2 as a putative novel broad cancer tumour suppressor and EFTUD2 as a putative novel multiple myeloma oncogene.
Modeling multi-stage disease progression and identifying genetic risk factors via a novel collaborative learning method
Authors: Xi Duo , Zhang Minjianan , Shang Muheng , Du Lei , Han Junwei ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2024

Motivation

Alzheimer’s disease (AD) typically progresses gradually for ages rather than suddenly. Thus, staging AD progression in different phases could aid in accurate diagnosis and treatment. In addition, identifying genetic variations that influence AD is critical to understanding the pathogenesis. However, staging the disease progression and identifying genetic variations is usually handled separately.

Results

To address this limitation, we propose a novel sparse multi-stage multi-task mixed-effects collaborative longitudinal regression method (MSColoR). Our method jointly models long disease progression as a multi-stage procedure and identifies genetic risk factors underpinning this complex trajectory. Specifically, MSColoR models multi-stage disease progression using longitudinal neuroimaging-derived phenotypes and associates the fitted disease trajectories with genetic variations at each stage. Furthermore, we collaboratively leverage summary statistics from large genome-wide association studies to improve the powers. Finally, an efficient optimization algorithm is introduced to solve MSColoR. We evaluate our method using both synthetic and real longitudinal neuroimaging and genetic data. Both results demonstrate that MSColoR can reduce modeling errors while identifying more accurate and significant genetic variations compared to other longitudinal methods. Consequently, MSColoR holds great potential as a computational technique for longitudinal brain imaging genetics and AD studies.

Availability and implementation

The code is publicly available at https://github.com/dulei323/MSColoR.
European Society of Endocrinology Curriculum and Training Recommendation in Endocrinology
Authors: Luger Anton , Durkan Maeve , Christ-Crain Mirjam , Marques Pedro
Published: December 2024

The European Society of Endocrinology (ESE) and the Union Européenne des Médecins Spécialistes (U.E.M.S.) Section and Board of Endocrinology have produced a Curriculum and Training Recommendation in Endocrinology to provide updated recommendations concerning the content and structure of postgraduate training. Cornerstones of the Curriculum are the integrity of Endocrinology not to be divided into subspecialties such as diabetology or thyroidology, recommendation of 6 years full-time training comprising 1–3 years (preferably 2–3 years) of General Internal Medicine followed by 3–5 years of specialist training in Endocrinology across 13 core areas. In addition to knowledge and experience in the many fields of Endocrinology, the Curriculum includes specific attitudes, communication skills, training to work in and lead multidisciplinary teams, resource management, quality assurance, human-error management, and critical incidents reporting as well as the commitment to life-long learning expected from a trainee and from an Endocrinologist. The Curriculum also includes requirements for training centres, for assessment of training and for competencies of trainers. The aim of the ESE Curriculum and Training Recommendation in Endocrinology is to harmonise postgraduate training and help provide the best medical care for patients with endocrine diseases across Europe.
The C. elegans LON-1 protein requires its CAP domain for function in regulating body size and BMP signaling
Authors: Serrano Maria Victoria , Cottier Stéphanie , Wang Lianzijun , Moreira-Antepara Sergio , Nzessi Anthony , Liu Zhiyu , Williams Byron , Lee Myeongwoo , Schneiter Roger , Liu Jun
Published: December 2024

The CAP (cysteine-rich secretory proteins, antigen-5, and pathogenesis-related) proteins are widely expressed and have been implicated to play diverse roles ranging from mammalian reproduction to plant immune response. Increasing evidence supports a role of CAP proteins in lipid binding. The Caenorhabditis elegans CAP protein LON-1 is known to regulate body size and bone morphogenetic protein (BMP) signaling. LON-1 is a secreted protein with a conserved CAP domain and a C-terminal unstructured domain with no homology to other proteins. In this study, we report that the C-terminal domain of LON-1 is dispensable for its function. Instead, key conserved residues located in the CAP domain are critical for LON-1 function in vivo. We further showed that LON-1 is capable of binding sterol, but not fatty acid, in vitro, and that certain key residues implicated in LON-1 function in vivo are also important for LON-1 sterol binding in vitro. These findings suggest a role of LON-1 in regulating body size and BMP signaling via sterol binding.
Proteolytic regulation of mitochondrial magnesium channel by m-AAA protease and prohibitin complex
Authors: Joshi Alaumy , Stanfield Rachel A , Spletter Andrew T , Gohil Vishal M
Published: December 2024

Mitochondrial membrane phospholipid cardiolipin is essential for the stability of several inner mitochondrial membrane protein complexes. We recently showed that the abundance of mitochondrial magnesium channel MRS2 is reduced in models of Barth syndrome, an X-linked genetic disorder caused by a remodeling defect in cardiolipin. However, the mechanism underlying the reduced abundance of MRS2 in cardiolipin-depleted mitochondria remained unknown. In this study, we utilized yeast mutants of mitochondrial proteases to identify an evolutionarily conserved m-AAA protease, Yta10/Yta12, responsible for degrading Mrs2. The activity of m-AAA protease is regulated by the inner mitochondrial membrane scaffolding complex prohibitin, and consistent with this role, we find that Mrs2 turnover is increased in yeast prohibitin mutants. Importantly, we find that deleting Yta10 in cardiolipin-deficient yeast cells restores the steady-state levels of Mrs2 to the wild-type cells, and the knockdown of AFG3L2, a mammalian homolog of Yta12, increases the abundance of MRS2 in a murine muscle cell line. Thus, our work has identified the m-AAA protease/prohibitin complex as an evolutionarily conserved regulator of Mrs2 that can be targeted to restore Mrs2 abundance in cardiolipin-depleted cells.
Metaxin-2 tunes mitochondrial transportation and neuronal function in Drosophila
Authors: Zhang Ting , Li Ling , Fan Xiaoyu , Shou Xinyi , Ruan Yina , Xie Xiaojun
Published: December 2024

Metaxins are a family of evolutionarily conserved proteins that reside on the mitochondria outer membrane (MOM) and participate in the protein import into the mitochondria. Metaxin-2 (Mtx2), a member of this family, has been identified as a key component in the machinery for mitochondrial transport in both C. elegans and human neurons. To deepen our understanding of Mtx2's role in neurons, we examined the homologous genes CG5662 and CG8004 in Drosophila. The CG5662 is a non-essential gene while CG8004 null mutants die at late pupal stages. The CG8004 protein is widely expressed throughout the Drosophila nervous system and is targeted to mitochondria. However, neuronal CG8004 is dispensable for animal survival and is partially required for mitochondrial distribution in certain neuropil regions. Conditional knockout of CG8004 in adult gustatory receptor neurons (GRNs) impairs mitochondrial trafficking along GRN axons and diminishes the mitochondrial quantities in axon terminals. The absence of CG8004 also leads to mitochondrial fragmentation within GRN axons, a phenomenon that may be linked to mitochondrial transport through its genetic interaction with the fusion proteins Marf and Opa1. While the removal of neuronal CG8004 is not lethal during the developmental stage, it does have consequences for the lifespan and healthspan of adult Drosophila. At last, double knockout (KO) of CG5662 and CG8004 shows similar phenotypes as the CG8004 single KO, suggesting that CG5662 does not compensate for the loss of CG8004. In summary, our findings suggest that CG8004 plays a conserved and context-dependent role in axonal mitochondrial transport, as well it is important for sustaining neuronal function. Therefore, we refer to CG8004 as the Drosophila Metaxin-2 (dMtx2).
Mining the cucumber core collection: Phenotypic and genetic characterization of morphological diversity for fruit quality characteristics
Authors: Lin Ying-Chen , Weng Yiqun , Fei Zhangjun , Grumet Rebecca
Published: December 2024

Commercial value of cucumber is primarily driven by fruit quality. However, breeding goals frequently focus on production constraints caused by biotic and abiotic stresses. As sources of resistances are often present in unadapted germplasm, we sought to provide morphological and genetic information characterizing the diversity of fruit quality traits present in the CucCAP cucumber core collection. These 388 accessions representing >96% of the genetic diversity for cucumber present in the U.S. National Plant Germplasm System harbor important sources of resistances and extensive morphological diversity. Data were collected for skin color, length/diameter ratio (L/D), tapering, curvature, and spine density for young fruits [5-7 days post-pollination (dpp)], and length, diameter, L/D, skin color, netting, seed cavity size, flesh thickness, hollowness, and flesh color for mature fruits (30-40 dpp. Significant associations of SNPs with each trait were identified from genome-wide association studies (GWAS). In several cases, QTL for highly correlated traits were closely clustered. Principal component analysis, driven primarily by the highly correlated traits of fruit length, young and mature L/D ratios, and curvature showed a clear divergence of East Asian accessions. Significant SNPs contributing to the longest fruits, including development-stage specific QTL, were distributed across multiple chromosomes, indicating broad genomic effects of selection. Many of the SNPs identified for the various morphological traits were in close vicinity to previously identified fruit trait QTL and candidate genes, while several novel genes potentially important for these traits were also identified.
Estimation of the Harvey Bradshaw Index from the Patient Reported Outcome-2 in Crohn’s Disease
Authors: Khanna Reena , Son Surim , Zou Guangyong , Roshanov Pavel S
Published: December 2024

Background

Many registrational trials in Crohn’s disease assess treatment efficacy with the 2-item Patient-Reported Outcome (PRO2), while the Harvey–Bradshaw Index (HBI) is prominent in pragmatic trials and clinical practice. The translation between PRO2 and HBI has not been established.

Methods

Data from a Phase 3 trial of vedolizumab in Crohn’s disease were used to determine the Pearson correlation between PRO2 and HBI. Linear regression was used to fit equations that estimate between indices; 95% prediction intervals were determined for HBI scores corresponding to PRO2 thresholds for disease activity. Internal validation of the conversion equations was performed using the bootstrap methods.

Results

PRO2 and HBI were highly correlated at baseline (r = 0.75 95% confidence interval (CI) 0.73-0.78; P < .001), induction (r = 0.87; 95% CI, 0.85-0.88; P < .001), and maintenance (r = 0.88; 95% CI, 0.85-0.90; P < .001). PRO2 and HBI change scores were moderately correlated (r = 0.72; 95% CI 0.69-0.75; P < .001) in induction and more strongly correlated during maintenance (r = 0.81; 95% CI 0.78- 0.84; P < .001). Regression equations for conversion of PRO2 to HBI from all cohorts (induction, maintenance, randomized, open-label) support an approximate conversion where HBI = 0.5 PRO2. As expected from the imperfect correlation between scores, the prediction intervals were generally wide. No evidence of overfitting was seen in bootstrap internal validation.

Conclusions

PRO2 and HBI correlate strongly and conversion between them is possible. These findings facilitate the practical application of trial results and clinical guidelines.
Histological, But Neither Clinical Nor Endoscopic Activity Predicts the Risk of Colectomy in Patients With Ulcerative Colitis Treated With Biologics
Authors: Zhao Mirabella , Riis Lene Buhl , Lo Bobby , Attauabi Mohamed , Ovesen Pernille Dige , Wewer Mads Damsgaard , Larsen Lone , Dige Anders , Hvas Christian Lodberg , Poulsen Anja , Christiansen Dagmar , Nagras Zainab Gassem , Dahlin Pernille , Petersen Andreas Munk , Bendtsen Flemming , Seidelin Jakob , Burisch Johan
Published: December 2024

Background

Biological treatment failure is common in patients with ulcerative colitis (UC), but the predictive value of baseline histological activity is unknown.

Aims

We aimed to investigate the associations between baseline histological activity and outcomes after biological treatment in patients with UC.

Methods

Adult biological-naïve patients with UC (n = 150) were followed prospectively during biological treatment. Histological activity was assessed using the Nancy Index and Geboes score. Endoscopic activity was assessed using the Mayo Endoscopic Subscore (MES). Associations with outcomes were assessed in multivariable models. Associations between histological, endoscopic, and biochemical activity were assessed using Spearman’s correlation.

Results

In biological-treated patients with UC, severe histological activity at baseline was independently associated with colectomy risk during the induction period (Nancy 2 vs 4: odds ratio [OR] 0.18, 95% CI 0.01-0.61, P = 0.024; Nancy 3 vs 4: OR 0.12, 95% CI 0.02-0.63, P = .019; Geboes 3 vs 5: OR 0.06, 95% CI 0.00-0.57, P = .033; Geboes 4 vs 5: OR 0.13, 95% CI 0.01-0.69, P = 0.032) and total follow-up (Nancy 2 vs 4: HR 0.23, 95% CI 0.06-0.98, P = 0.046; Nancy 3 vs 4: HR 0.13, 95% CI 0.04-0.47, P = 0.002; Geboes 4 vs 5: HR 0.28, 95% CI 0.08-0.93, P = 0.038). Meanwhile, baseline MES was not independently associated with colectomy risk. Histological activity was correlated with MES and the levels of C-reactive protein, hemoglobin, and albumin, but not calprotectin.

Conclusions

Severe histological activity at baseline as characterized by a higher Nancy Index or Geboes score independently predicted colectomy risk in biological-treated UC patients, whereas MES did not. Thus, histological assessment should be encouraged before initiating biological treatment.
Fleeing Deprivation: Deducing Non-Refoulement Obligations from Economic, Social and Cultural Rights
Authors: Ferolla Vallandro do Valle Mariana
Published: December 2024

While the principle of non-refoulement is today acknowledged as the cornerstone of the general human rights regime protecting people on the move, developments of the content of this principle have focused on risks of harm to civil and political (CP) rights. Factors affecting economic, social and cultural (ESC) rights have been addressed only indirectly, where socio-economic deprivation is deemed to amount to inhuman and degrading treatment. Nevertheless, not every instance of severe harm to ESC rights will necessarily equate to ill-treatment. Failure to recognize an autonomous basis for non-refoulement obligations in ESC rights may thus lead to gaps in protection and contribute to the trend of underdevelopment of the legal content of ESC rights in comparison to CP ones. This article thus addresses whether obligations of non-refoulement can be autonomously deduced from treaty provisions on ESC rights. In doing so, it delves into the legal basis upon which the principle of non-refoulement in general human rights law is built, according to the practice of international human rights bodies in interpreting and applying this principle. The article takes into account the practice of all regional human rights frameworks (African, European, and Inter-American) and United Nations treaty bodies that have dealt with the principle of non-refoulement, seeking to discern a common foundation to this principle’s rationale and scope. It is submitted that non-refoulement qualifies as a positive obligation to prevent risks of severe harm to rights by third parties and is, accordingly, inherent in all human rights. The compatibility between ESC rights obligations and non-refoulement is then analysed, and ways to render practicable the application of non-refoulement in connection with these rights are identified, focusing on immediate obligations stemming from ESC rights and minimum threshold obligations. Finally, objections to non-refoulement based on socio-economic grounds, namely concerns regarding the potential increase of mass migratory influxes and the added value of such a norm, are addressed. The article concludes that neither legal nor non-legal considerations bar deducing non-refoulement obligations from ESC rights and that much of the reasoning applied to non-refoulement assessments in cases involving CP rights can be transposed to cases involving ESC rights, especially when immediate ESC rights obligations are at stake.
Concentration inequalities for sums of Markov-dependent random matrices
Authors: Neeman Joe , Shi Bobby , Ward Rachel
Published: December 2024

We give Hoeffding- and Bernstein-type concentration inequalities for the largest eigenvalue of sums of random matrices arising from a Markov chain. We consider time-dependent matrix-valued functions on a general state space, generalizing previous results that had only considered Hoeffding-type inequalities, and only for time-independent functions on a finite state space. In particular, we study a kind of non-commutative moment generating function, provide tight bounds on this object and use a method of Garg et al. (A matrix expander Chernoff bound. In Proceedings of the 50th Annual ACM SIGACT Symposium on Theory of Computing, STOC 2018, page 1102–1114, New York, NY, USA, 2018. Association for Computing Machinery) to turn this into tail bounds. Our proof proceeds spectrally, bounding the norm of a certain perturbed operator. In the process we make an interesting connection to dynamical systems and Banach space theory to prove a crucial result on the limiting behaviour of our moment generating function that may be of independent interest.
Power Grabs from the Top: A Database of Self-Coups
Authors: Goldsmith Arthur A
Published: December 2024

This research note introduces new global data on self-coups—rapid moves by sitting executive leaders to “overthrow” their own governments and illegitimately maintain or extend power. Self-coups are distinct from ordinary coups (sudden illegal attempts by other elites to topple the sitting executive) and overlap with incumbent takeovers (incremental quasi-legal steps by the sitting executive to amass power). Still, there is conceptual discord about what delineates self-coups and a resultant lack of consensus about basic facts, even about where and when self-coups have happened. To provide a firmer foundation for investigating the self-coup phenomenon systematically, I draw from eight datasets and original data collection and coding to present comprehensive data on 147 individual events (plus 90 candidate incidents that did not fully meet the criteria) in the 1950–2022 period. The dataset provides information on the perpetrators, targets, flashpoint dates, and methods of these events. Illustrative statistical analysis suggests that following a self-coup, the level of international economic aid tends to have a negative effect on the probability that a country will hold competitive elections. Future research may apply these data for a better understanding of the causes of self-coups and the long-term effects of self-coups on political and economic development.
Exploring Household Preferences for Visualising Consumption Information: Towards Data Physicalizations to Promote Sustainable Practices
Authors: Perera Dushani , Verdezoto Dias Nervo , Gwilliam Julie , Eslambolchilar Parisa
Published: December 2024

This paper explores household preferences for visualizing consumption data and investigates the potential of data physicalizations to enhance user engagement and promote sustainable practices within households. We conducted semi-structured interviews with thirteen households, utilizing a combination of images and low-fidelity prototypes to gain insights into participants’ preferences, ideas and feedback on visualizing consumption information. We requested participants to discuss an object in their home that symbolizes sustainability. The results revealed different emotional responses, from empathy to repulsion, triggered by different visual representations. Our findings also identified certain physical objects and locations within the household that play a role in fostering family collaboration towards sustainable practices. Participants preferred having a physical representation of their consumption data within their homes over a screen-based display. In light of these findings, we open space to consider designing physicalizations that encourage collaboration, enhance user engagement and motivate households to reduce their consumption.
Duty to act on knowledge: precautions, intelligence and the law of armed conflict
Authors: Breeze Emma J
Published: December 2024

As Einstein famously said ‘[t]hose who have the privilege to know have the duty to act…’ (Albert Einstein c. 1929). This article takes the precautionary obligations of the Law of Armed Conflict (LOAC) to argue that parties to an armed conflict are obliged to act on their intelligence to minimize the harm to civilians caught up in the conflict. As such, it assesses the relationship between intelligence and the precautions to be taken against attacks under LOAC. It uses the context of Improvised Explosive Devices (IEDs) to illustrate some of the challenges that may be faced in interpreting the law and to demonstrate how significant a thorough understanding of this obligation could be in protecting civilians. I argue that states have an obligation to use their actionable intelligence to protect civilians under their control and for more than merely militarily advantageous reasons. However, the critical challenge is in establishing the scope of the obligation in terms of control and temporality, with limited judicial handling reducing clarity. Nonetheless, I contend that there is a legal obligation on states, beyond the territorial state, to proactively use intelligence during armed conflict to protect civilians from IEDs as well as other evolving threats of armed conflict.
Surgical risk and cause of death among octogenarian and nonagenarian patients with colorectal cancer: a Japanese multicenter study
Authors: Hashimoto Shintaro , Nonaka Takashi , Tominaga Tetsuro , Shiraishi Toshio , Noda Keisuke , Ono Rika , Hisanaga Makoto , Takeshita Hiroaki , Fukuoka Hidetoshi , Fukuoka Kazuo To , Tanaka Kenji , Kunizaki Masaki , Sawai Terumitsu , Matsumoto Keitaro
Published: December 2024

Background

The number of elderly people undergoing surgery for colorectal cancer has been increasing. We examine prognosis, including risks of surgery by age and cancer- and noncancer-related deaths.

Methods

This study retrospectively reviewed 1830 patients who underwent curative resection colorectal surgery. Patients were divided into oldest-old (>85 years old, n = 49), elderly (75–84 years old, n = 637), and young (<75 years old, n = 1144) patient groups.

Results

Physical status was poorer (P < .001), postoperative complications were more frequent (49.0% vs. 20.9% vs. 18.4%; P < .001), and adjuvant chemotherapy was less frequent (0% vs. 44.3% vs. 83.5%; P < .001) as patients got older. Multivariate analysis revealed oldest-old [odds ratio (OR) 4.373, 95% confidence interval (CI) 2.362–8.110; P < .001] as independent predictors of postoperative complications. Elderly patients [hazard ratio (HR) 2.494, 95%CI 1.707–3.642; P < .001], oldest-old patients (HR 5.969, 95%CI 3.229–11.035; P < .001), poor physical status (HR 2.546, 95%CI 1.694–3.827; P < .001), and postoperative complications (HR 1.805, 95%CI 1.252–2.602; P = .001) were predictive factors for noncancer-specific survival.

Conclusions

Elderly patients had many complications and a higher risk of dying from other causes. Surgical risk and general condition must be considered when deciding the appropriateness of surgery and adjuvant therapy.