bluuebunny/crossref_metadata_2025 huggingface dataset:
Counting Paul
Authors: White Benjamin L
Published: February 2025

This book argues that there is no mathematical solution to the question of the authorship of the Pauline Epistles in the New Testament. For more than two hundred years, linguistic features of the Pauline Epistles have been counted, averaged, and compared. The book shows that, by measuring one text against another, scholars have thought that the authentic Pauline stylome would emerge as the incontrovertible standard for uncovering canonical forgeries in the Apostle’s name. It describes how the analysis of authorial style took on increasing argumentative weight as a way out of the many subjective and circular decisions that normally attended arguments over the authenticity of the Pauline Epistles as they began to develop in the nineteenth century. Tracing the long history of the computational approach to the Pauline authorship problem, this book exposes the ideological foundations and sloppy science of much of the work, even in its more sophisticated forms in the computer age, and ultimately argues that Pauline biography ought not be written from fewer sources than what the New Testament has given us, but rather more. It advocates for a more expansive vision of what might count as Pauline by reorienting our focus away from internal criteria, like appeals to style, and toward external criteria, like the reception of Paul in the generations after his death.
Studying Paul
Authors: White Benjamin L
Published: February 2025

This chapter describes the contours of the discipline of Pauline Studies and argues that its historiographical practices are still grounded in F. C. Baur’s powerful double move in the early nineteenth century—the delimiting of the authentic Pauline Epistles to just four (i.e., fewer than what the canon has given us) and the devaluation of Acts as a historical account. It shows how arguments about authenticity have always devolved into circular and subjective forms of reasoning and how the way out of such a problem has often been to secure a mathematical solution based on quantifying the differing literary styles of the Epistles. The chapter posits that in many cases math and science as applied to the Pauline authorship problem has been little more than scientificity, and that fuzzy math and statisticulating have papered over decisions already assumed to be true on account of the theological preferences of largely Protestant researchers.
Gaming Paul
Authors: White Benjamin L
Published: February 2025

This chapter identifies how best practices in the wider field of computational stylistics should apply to the Pauline authorship problem. It discusses recent developments in forensic stylometry and describes the results of a set of novel stylometric authorship tests on the Pauline Epistles. The chapter shows, based on these tests, that there is little reason to think that listed co-authors in the Pauline Epistles have affected their Pauline style, or that the scribal transmission of the Pauline Epistles has obscured our ability to make reasonable inferences about authorship from authorship attribution tests. A final set of clustering tests of thirty-three early Christian epistles provide results that can be reasonably interpreted in a number of different ways, depending on the prior assumptions of the interpreter. The chapter concludes that what “counts” for Paul depends on tradition, not mathematics. One does not find a Cartesian foundation in the Paul-as-math-problem approach.
Theorizing Paul
Authors: White Benjamin L
Published: February 2025

This chapter returns to the authenticity paradigm described in Chapter 1 and draws out the consequences of the fact that its ace in the hole—the Paul-as-math-problem approach—cannot deliver on its promises and has been driven by interests very distant from Paul’s. There is no stylometric justification, in particular, for the seven-letter “consensus.” The chapter argues that nothing less than a full turn toward, appreciation of, and vigorous engagement with the early reception of Paul will provide the proper leverage for gaining traction on questions related to Paul’s biography and to questions of epistolary authenticity. It defends this position both from the literary evidence and from a plausible account of how Paul’s reputation was secured, contested, and transmitted both during his own lifetime and in the several generations after his death. The argument pulls Pauline Studies closer to Historical Jesus Studies and opens up new vistas for what might “count” for Paul.
What is a State?
Authors: Lemke Douglas
Published: February 2025

In this chapter, I take a deep dive into conceptual and operational definitions of “the state.” Most scholars conceive of states as sets of governing institutions supervising a permanent population within a defined territory. But the operational definition employed in past research identifies as states only those satisfying minimum population thresholds and enjoying some form of diplomatic recognition of their sovereignty. The mismatch between concept and measure introduces inaccuracy into existing analyses of state death and prevents us from testing some theories. The territorial contender dataset is described; it provides a wealth of information about the nonsovereign states (e.g., territorial contenders), which are the needed complement to sovereign states in studies of state death specifically and of IR more generally.
The Norm Against Conquest and the Survival of States
Authors: Lemke Douglas
Published: February 2025

In this chapter, I evaluate the strong claim that state death is less likely after 1945 because a norm against conquest arose after World War II. I also evaluate various ways the norm against conquest might have prolonged state life: through enhanced commercial relations, through an expanded network of international organizations, or through supportive interventions by the superpowers. I show state death is indeed less likely after 1945—but only for territorial contenders! Norms are supposed to govern interactions between sovereign states, so this finding is quite anomalous. Upon further investigation, I demonstrate my contradictory finding arises because I only study the developing world. The existing finding about the norm against conquest is not replicated when the developed world is excluded. I consider what these findings mean for what we know about state death and for how we study the role of norms in international relations.
Political Geography and the Survival of States
Authors: Lemke Douglas
Published: February 2025

In this chapter, I consider the hypothesis that buffer states are especially likely to die because the rivals on either side of them have strong incentives to absorb their territories. I also consider the counterargument that territorial disagreements cause both buffer status and state death. After overcoming the difficulty of measuring buffer status and territorial disagreements for territorial contenders, I find strong support for the hypothesis about buffer states but no support for the argument about territorial disagreements. I also show that buffer states are more likely to lose wars, and this contributes to their greater likelihood of suffering state death.
Introduction
Authors: Kalaycioglu Elif
Published: February 2025

The International Criminal Court’s prosecution of al-Mahdi for the destruction of Sufi shrines in Timbuktu suggests that humanity and its shared memory have moral and juridical standing in global politics. That standing, importantly, was tethered to the World Heritage regime’s designation of certain cultural sites as humanity’s shared heritage. But what does it mean to produce a shared cultural history of humanity, and what do those efforts produce in the world? This chapter lays out the book’s analysis of the productive politics of World Heritage across three visions of humanity, with a focus on resulting social and political orders. It places the book in conversation with the interdisciplinary scholarship on World Heritage, and outlines its contributions to International Relations (IR) debates on humanity’s global politics, global politics of culture, and the regime’s relevance for thinking about the liberal international order.
Humanity is What States Make of It?
Authors: Kalaycioglu Elif
Published: February 2025

This chapter analyzes the World Heritage regime (2010–2022) under the shadow of broader global political dynamics, which include the assertion of state wills and the contestation of liberal visions in a context of multipolarity. In this context, a new iteration of humanity emerged as a diverse community that is adequately represented by an aggregation of states, with previously analyzed visions of humanity also still in circulation. Humanity, I posit, endures as the subject that makes possible states’ claims to more-than-national cultural and historical value, and as the subject in relation to which global political visions are adjudicated and launched. Further, what upholds this third iteration of humanity, against objections within and beyond the regime, are the institutional infrastructures that continue to produce the List of World Heritage sites with universal value. The chapter concludes with implications of this period’s politics of humanity for peace and solidarity by focusing on the nominations for the Silk Roads and the Bikini Atoll Nuclear Test Site, and recent debates on interpretive practices.
The Target Phenomenon
Authors: Salje Léa
Published: February 2025

Chapter 1 sets out the target phenomenon of articulatory self-knowledge in theory-neutral terms. It does this by using an extended example to identify a three-part epistemic-phenomenological structure in common to all cases of the articulatory self-knowledge. This structure is offered as definitional of our target phenomenon. With the target phenomenon on the table, the chapter then elucidates the philosophical task ahead. This will look different for so-called inflationist accounts (that posit a complete and determinate thought at the onset of the phenomenon) and deflationist accounts (that don’t). The chapter ends by saying something briefly about the space of positions to be considered over the next three chapters.
Conversation
Authors: Salje Léa
Published: February 2025

Chapter 6 investigates the cognitive benefits we can gain from engaging in conversation with others. It makes the case for three such benefits: information transmission (the gaining and imparting of information), rational answerability (the felt pressure towards only expressing content one is willing to expose to external scrutiny), and articulatory explicitation (the felt pressure towards putting one’s thoughts into words). The third of these results in a social version of the phenomenon of articulatory self-knowledge. I argue that the social version of our target phenomenon is the primary one, and one that couldn’t be easily intersubstituted by a non-human source of articulatory pressure. It turns out that we need one another to cognitively flourish. The last section of the chapter considers how this social good of conversation is distributed among different groups.
Art
Authors: Salje Léa
Published: February 2025

Chapter 7 develops a framework for thinking about articulatory self-knowledge in cases in which it results not in a natural language utterance, but in artistic self-expression. It does this by offering a definition of the key relation of paraphrase holding between the input thought and its outward expression that does not stipulatively exclude the possibility of non-(literal-)verbal expression. It then makes a positive case for the claim that artworks can sometimes play the stabilising cognitive role that is played in the canonical case of articulatory self-knowledge by natural language sentences. The rest of the chapter defends this extension of the moderate deflationist view of articulatory self-knowledge from a number of objections, and illustrates the proposed extension with an extended example.
Care home quality and ‘inappropriate’ emergency healthcare use—failing to engage with complexity
Authors: Harrad-Hyde Fawn , Burton Jennifer Kirsty
Published: February 2025

Care home residents are more likely to experience unplanned, emergency healthcare than those living elsewhere in the community. This can be potentially burdensome for both individual residents and healthcare systems. Academic and policy attention has focussed on quantifying this resource use, exploring potential causes and reducing unplanned emergency healthcare. Considerable attention has been placed on emergency healthcare that may be ‘inappropriate’ or ‘avoidable’. In this commentary, we problematise such concepts. We suggest that the absence of an agreed definition can lead to wide variation in estimations which fail to acknowledge the complexity of care home residents’ needs and their right to timely healthcare support. We draw attention to the impact of popular discourse in this area as potentially stigmatising to care home organisations, staff and residents. We argue that emergency healthcare use data alone is insufficient to measure and evaluate the quality of care provided by care homes. We propose a move away from over-simplistic distinctions, between emergency healthcare that is or is not ‘appropriate’, to develop more nuanced conceptualisations that account for the complexity involved in providing healthcare support to people living in care homes. People living in care homes have significant healthcare needs. It is necessary that models of care supporting homes are resourced to respond and support care home professionals. Rather than focusing solely on quantifying emergency healthcare use, acknowledging and embracing complexity will help to refocus our efforts and redesign our services around both individual and population needs, rather than around existing systems.
18 iNPWT versus standard dressing on groin surgical incisions after revascularization surgery: PICO-vasc randomised trial
Authors: Lorenzo Laura Rodriguez , Cañas Elena Gonzalez , Madrazo Gonzalez Zoilo , Salto Eduardo Arrea , Gimenez Gaibar Antonio , Radua Jana Merino
Published: February 2025

Objective

This study assessed the potential benefit of applying incisional negative pressure wound therapy (iNPWT) in patients undergoing revascularisation due to peripheral arterial disease.

Design

A prospective, randomised, controlled trial was conducted comparing the inguinal application of iNPWT versus standard surgical dressing. Patients were enrolled from February, 2021 to November, 2022.

Methods

One hundred and thirty-three groin incisions were randomised (66 intervention group, 67 control group). Randomisation sequence was carried out by permuted blocks and allocation assigned by opening opaque envelopes once the revascularisation procedure finished. Wound healing and complication rates were assessed at postoperative days 5, 14 and 30. The primary and secondary endpoints were: 30-day postoperative surgical site infection (SSI) and surgical site occurrence (SSO) rates, defined as surgical wound complication other than SSI. Postoperative SSI was defined according to the Center for Disease Control and Prevention (CDC) criteria. SSO included: wound dehiscence, seroma or lymphocele, haematoma, and lymphorrhagia. The study was registered at ClinicalTrails.gov database (NCT04840576) and reported according to the CONSORT guidelines.

Results

iNPWT did not alter the 30-day inguinal SSI and SSO rates (16.7% versus 20.9%, P = 0.53 and 37.9% versus 44.8%, P = 0.42, respectively). The use of iNPWT showed a reduction in early-SSO rate (19.7% versus 35.8%, RR 1.45, 95% c.i. 1.047–2.013), wound dehiscence (0% versus 6%, P = 0.044) and postoperative seroma (4.6% versus 19.4%, P = 0.014).

Conclusion

Inguinal postoperative use of iNPWT proved to be an effective preventive tool, with significant reductions in early-SSO rate, wound dehiscence, seroma, but did not alter the 30-day SSI and SSO rates.
27 Reduction of the duration of antibiotic therapy in surgery through a specific nationwide stewardship program. A prospective cohort study (2019–2022)
Authors: Batlle Maria , Hernández Sergi , Padulles Ariadna , Boix-Palop Lucia , Giménez Montserat , Garcia Maria Pilar , Grau Santiago , Horcajada Juan P , Badia Josep M
Published: February 2025

Aim

Prolonged antibiotic treatments contribute to increasing antimicrobial resistance. Current guidelines recommend 5–7 days of treatment in patients with surgical infection with an adequate source control. Antibiotic stewardship aim to optimize the use of antibiotics, including their duration. The 7VINCut nationwide intervention aims to reduce the duration of treatments to <7 days in surgical patients.

Methods

Prospective cohort study conducted in 37 hospitals in 2019–2022. Patients admitted to surgical services with antibiotic treatment >7 days were analysed. The 7VINCut teams met weekly and made written recommendations in the electronic medical record. Indication for treatment, quality of source control, type of antibiotics, recommendations issued, and adherence to them were analysed. Temporal trends in the percentages of patients admitted with antibiotic treatment and those with treatment >7 days were evaluated using a linear regression model and Pearson's correlation coefficients.

Results

44 702 patients with antibiotic treatment were examined. Of these, 6163 (13.8%) had treatments >7 days. A total of 5606 stewardship interventions were performed (90% of the target population), primarily in general surgery (5704; 90%) and urology (497; 8.9%). The main sources of infection were intra-abdominal (73%), skin/soft tissues (10%) and urinary (9.3%). The septic focus was considered controlled only in 60.2% of cases. Out of 6236 antibiotic prescriptions, the most frequently analysed drugs were piperacillin/tazobactam (27.1%), metronizadole (14.4%), amoxicillin/clavulanate (12.9%), meropenem (12.8%), ceftriaxone (11.6%) and ciprofloxacin (8.1%). Antibiotics with a high ecological impact account for 68.3% of the prescriptions evaluated. The main issued recommendations were: treatment discontinuation (34.1%), maintenance (41.0%) or de-escalation (15.3%), and were followed in 5179 cases (adherence 92.4%). With an adequate source control, the most frequent recommendation was to terminate treatment (49.6%, 1673 cases). Throughout the study period, a significant decrease in the percentage of prolonged treatments was observed (−40.1%, Pc = −0.39; P = 0.006).

Conclusions

The 7VINCut program, including surgeons in the multidisciplinary antibiotic stewardship teams, achieved a reduction in antibiotic treatments lasting over 7 days in surgical departments. The majority of stewardship interventions were carried out in general surgery departments, in cases of intra-abdominal infection and in beta-lactam and carbapenem antibiotics. Overall adherence to the recommendations issued by the teams was 92.4%.
28 The effect of the number of operating room door openings on surgical site infection risk: an individual patient data meta-analysis
Authors: Groenen Hannah , Jalalzadeh Hasti , Bontekoning Nathan , Orsini Ricardo G , Eskes Anne M , de Jonge Stijn W , Wolfhagen Niels , Hannink Gerjon , Boermeester Marja A
Published: February 2025

Background

The effect of the number of door openings in the operating room (OR) on surgical site infections (SSI) risk remains a controversial topic. Many SSI prevention bundles include a restriction on the maximum number of door openings as intervention, often to ten per hour. However, existing evidence is limited and heterogeneous. This individual participant data (IPD) meta-analysis aims to evaluate the effect of the number of door openings in the OR on SSI occurrence.

Methods

We searched MEDLINE (Pubmed) and Embase (Ovid) up to 15 January 2024, for studies investigating the effect of the number of door openings on SSI incidence. Authors of eligible studies were invited to collaborate. IPD were merged and analysed with a logistic regression model with mixed-effects. This study is registered with PROSPERO, CRD42022309958.

Findings

IPD from eight observational studies, encompassing 4412 patients, revealed a 6.0% overall SSI incidence. The logistic regression model with mixed-effects indicated a difference in SSI risk for each extra door opening per hour (OR 1.01 [95% c.i. 1.004–1.02]; very low certainty of evidence). To enhance the practical applicability, door openings were categorised. Inconclusive evidence was found regarding SSI risk difference for 10 to 31.7 door openings per hour (OR 1.11 [95% c.i. 0.77–1.59]) compared to 10 or fewer. While for more than 31.7 door openings per hour (OR 1.52 [95% c.i. 1.02–2.26]) a conclusive difference in SSI risk was found compared to 10 or fewer.

Interpretation

Very low certainty of evidence indicated a marginal increase in SSI risk for each extra door opening per hour. However, a restriction on the number of door openings in the OR to a maximum of 10 per hour has little to no effect on SSI risk.

Funding

This systematic review is funded by the Dutch Stichting Kwaliteitsgelden Medisch Specialisten (SKMS, Foundation Quality Funds Medical Specialists).
7 Predictive factors of complicated appendicitis in children
Authors: Pereyaslov Andriy , Sodoma Oleg , Stenyk Roman , Malovanyy Bohdan
Published: February 2025

Acute appendicitis represents one of the most common abdominal surgical emergency among pediatric population. Complicated appendicitis (gangrenous, perforated) is an extremely severe clinical situation because misdiagnosis led to delayed treatment and the development of complications, such as peritonitis, sepsis, bowel obstruction, and abscess formation. By that, clear pre-operative identification patients with complicated appendicitis are challenging. The aim of this study was to evaluate the different scoring systems and laboratory markers for the prediction of complicated appendicitis at admission. A retrospective medical records review of 1693 patients with acute appendicitis from 2017 to 2022 was performed. All patients divided on two groups: first with simple appendicitis (1167 patients) and second with complicated form (526 patients). Data analyzed included appendicitis inflammatory response score (AIRS) and pediatric appendicitis score (PAS), white blood cell (WBC) count, neutrophil count, neutrophil lymphocyte ratio (NLR), C-reactive protein (CRP) level, and sodium plasma level. Receiver operating characteristic (ROC) curve with the area under the curve (AUC), specificity, sensitivity, positive prognostic value (PPV), negative prognostic value (NPV), and likelihood ratio (LR) were determined for all these markers. ROC analysis showed that for discriminating between complicated and simple appendicitis the high predictive value had NLR (AUC—0.848, sensitivity—90.3%, specificity—89.9%, PPV—98.9%, NPV—46.6%, LR(±)—8.94/0.11), low sodium level (AUC—0.801, sensitivity—90.3%, specificity—84.0%, PPV—98.5%, NPV—27.5%, LR(±)—5.21/0.21), and AIRS (AUC—0.774, sensitivity—82.0%, specificity—70.9%, PPV—98.2%, NPV—17.1%, LR(±)—2.82/0.25). WBC, neutrophil count, CRP level, and PAS had limited value for the pre-operative distinguishing complicated appendicitis. Thus, NLR, sodium plasma level, and AIRS permit with the high degree of reliability preoperatively select patients with suspected complicated appendicitis. Moreover, these markers is not expensive to measure, is easily available, and the short time required for analysis is valuable in the emergency department.
38 Optimising infected evisceration with NPWTi and mesh mediate closure—a hernia should no longer be accepted as reasonable result
Authors: Johnston Magnus , Kovacs Luca Kovacs , Damaskos Dimitrios , Zanellato Artur
Published: February 2025

Background

The infected open surgical abdomen can pose a considerable challenge and often requires multiple stage operations with a combination of temporary and definitive closure techniques with the aim to prevent long-term morbidity caused by the loss of abdominal domain. There is a great range of options of techniques for both temporary abdominal closure commonly the Bogota bag, vacuum-assisted closure (VAC) and similarly with definitive reconstruction such as the use of mesh and components separation. In our case we aimed to demonstrate the use of a novel, modern approach to the closure of a complex infected abdominal wall dehiscence using a negative pressure Negative Pressure Wound Therapy With Instillation (NPWTi ) in association with Abthera@ system.

Case Report

A 50 year-old presented with a gangrenous caecal volvulus on the background of severe sarcopenia and hypoalbuminaemia. The patient underwent an emergency right hemicolectomy with an end ileostomy. The abdominal wound became infected and also developed large bilateral flank collections with positive yeast and vancomycin-resistant enterococcus which resulted in a day 8 wound dehiscence managed with laparostomy and negative pressure (Abthera). On the third operation the peritonitis and sepsis had improved, ergo the open abdomen and loss of domain was thus managed with mesh mediated traction with NPWTi (negative pressure wound therapy with installation) to aid removal of contamination, closure and granulation of mesh whilst protecting from mesh infection. In the 4th intervention, the mesh was trimmed and tightened for gradual closure. On the subsequent washouts the midline reached the point of easy closure with minimal tension. The closure was obtained by suturing both mesh and midline with 2-0 poliproleme. The mesh became intimately attached to aponeurosis and rectus muscle with subsequent granulation tissue allowing skin was closed with NPWT.

Educational Highlights

Normal polipropelene was successfully used for closure of infected wound dehiscence.Severely sarcopenic patient had a successful closure and no hernia was found on 1.5 years follow-up so far.

Conclusions

Usually an infected evisceration is seen as such difficult complication that leaving the abdomen open to heal by second intention and treat the hernia after several months is usually an accepted measure worldwide, but most of the times the hernia became a chronic disease with several recurrences and complex operations. The use of negative pressure with instillation can be seen to improve healing time, removal of contamination and reduce the potential risk of developing incisional hernia. Although an initial short follow up, it is expect with this technique that hernia formation should be avoided.
Outcomes of Patients with Cancer Admitted with Heart Failure-Associated Cardiogenic Shock
Authors: Liu Olivia , Soo Steven , Bloom Michelle , Alvarez-Cardona Jose , Katz Jason N , Cheng Richard K , Yang Eric H , Leiva Orly
Published: February 2025

Background

Acute decompensated heart failure (HF) can progress to cardiogenic shock, and patients with cancer are at an increased risk of HF compared to patients without cancer. However, limited data exist on outcomes of patients admitted for HF-related cardiogenic shock (HF-CS) with cancer versus without cancer.

Methods

Adult patients admitted for HF-CS between 2014-2020 were identified using the National Readmission Database. Propensity score matching (PSM) was used to match 1 patient with cancer to 10 patients without cancer. Primary outcomes were in-hospital death, major bleeding, and thrombotic complications. Exploratory outcomes were 90-day readmission rates among patients who survived initial hospitalization. Temporal trends were also explored.

Results

Of 137,316 admissions for HF-CS, 7,306 (5.3%) had active cancer. After PSM, patients with cancer had increased odds of in-hospital death (OR 1.12, 95% CI 1.06 - 1.18), thrombotic complications (OR 1.12, 95% CI 1.03 - 1.21), and major bleeding (OR 1.23, 95% CI 1.17 - 1.31) compared to patients without cancer, with risks differing by cancer type. In exploratory analyses, rates of readmission were similar for patients with and without cancer. From 2014-2020, patients with cancer had no significant change in in-hospital mortality (ptrend = 0.43), while patients without cancer had decreased mortality over time (ptrend < 0.001).

Conclusions

Among patients admitted for HF-CS, patients with cancer are at increased risk of in-hospital death, thrombotic complications, and major bleeding compared to patients without cancer. Future studies are needed to guide nuanced evaluation and management of this population to improve outcomes.
Rare ZMPSTE24 variants increase risk of hypertriglyceridemia and metabolic syndrome
Authors: Le Collen Lauriane , Desgrouas Camille , Lukas Croisier Céline , Creugnet Brunot , Dechaume Aurélie , Toussaint Bénédicte , Vaillant Emmanuel , Amanzougarene Souhila , Buse Falay Emmanuel , Derhourhi Mehdi , Lourdelle Alexandre , Delemer Brigitte , Bonello-Palot Nathalie , Vaxillaire Martine , Badens Catherine , Froguel Philippe , Bonnefond Amélie
Published: February 2025

Objective

The global increase in the prevalence of metabolic syndrome represents a significant public health concern. Rare biallelic pathogenic variants in ZMPSTE24 have been identified as the cause of mandibuloacral dysplasia type B, i.e. a lipodystrophy syndrome associated with metabolic complications. The role of monoallelic pathogenic variants in ZMPSTE24 concerning metabolic syndrome remains uncertain.

Design

Case report and systematic review of literature.

Methods

We investigated a Wallisian family with FPLD and metabolic syndrome via whole-exome sequencing. We performed functional analyses of an identified rare ZMPSTE24 variant. To broadly assess the effect of heterozygous pathogenic ZMPSTE24 variants on FPLD-associated phenotypes, and metabolic syndrome, we used the Human Gene Mutation Database [HGMD] and 200K exome data from UK Biobank.

Results

We investigated a Wallisian family where a 40-year-old female with metabolic syndrome was found to carry a rare heterozygous missense variant in ZMPSTE24. Functional assays showed a decreased prelamin to lamin A maturation and accelerated senescence. In silico analysis demonstrated that this variant might disrupt the lamin A binding site. We then analyzed the impact of monoallelic pathogenic ZMPSTE24 variants on metabolic traits using data from the HGMD and the UK Biobank. In HGMD, ZMPSTE24 variants carriers presented with dyslipidemia and hepatic steatosis. In the UK Biobank, monoallelic pathogenic variants were associated with an increased risk of hypertriglyceridemia, with a trend toward metabolic syndrome.

Conclusions

This study underscores the association of ZMPSTE24 rare variants with metabolic disorders and emphasizes the need for further research to clarify their clinical implications.
Differential cardiovascular impacts of sodium salts: unveiling the distinct roles of sodium chloride and sodium bicarbonate—consequences for heart failure patients
Authors: Sadki Dalil , Fawaz Sami , Liegey Jean-Sebastien , Pucheu Yann , Boulestreau Romain , Beuque Gauthier , Foucher Jeanne , Hein Louise , Couffinhal Thierry
Published: February 2025

Misconceptions surrounding sodium compounds, particularly the interchangeable use of sodium and sodium chloride (table salt), persist within the medical community, influencing dietary recommendations and patient management especially in heart failure (HF) patients with chronic kidney disease (CKD). This narrative review aims to dissect these misconceptions and discusses the physiological impacts of sodium, chloride, and sodium bicarbonate on cardiovascular (CV) physiology. The conflation of sodium and sodium chloride in dietary recommendations has obscured critical differences in their physiological effects. While sodium chloride is traditionally linked to hypertension, emerging evidence suggests that chloride, rather than sodium, may be the primary driver of hypertension and activation of the renin-angiotensin-aldosterone system. In contrast, sodium bicarbonate, when administered orally, seems to exert minimal effects on blood pressure and plasma volume, offering a promising and safe way for managing HF patients with renal insufficiency. Indeed, the therapeutic benefits of sodium bicarbonate in CKD patients, including preservation of muscle mass, slowing of renal function decline, lowering of all-cause mortality, and improved nutritional status, are quite proven; this underscores its potential utility in patients suffering from both HF and renal insufficiency. Despite concerns about metabolic alkalosis, recent studies suggest that judicious sodium bicarbonate therapy may mitigate major adverse cardiac events without exacerbating HF. This review advocates for a paradigm shift in CV medicine, urging clinicians to discern between sodium chloride and other sodium salts, particularly sodium bicarbonate, in patient care. By elucidating these distinctions, clinicians can tailor dietary recommendations and therapeutic interventions to optimize outcomes for HF patients with CKD and address the multi-faceted complexities of atherosclerotic disease.
Habitat management and restoration as missing pieces in flats ecosystems conservation and the fishes and fisheries that they support
Authors: Griffin Lucas P , Danylchuk Andy J , Casselberry Grace A , Brownscombe Jacob W , Robichaud Jessica A , Piczak Morgan L , Haley Anne L , Morely Danielle , Cooke Steven J
Published: February 2025

Flats ecosystems are dynamic, shallow, nearshore marine environments that are interconnected and provide immense ecological and socio-economic benefits. These habitats support a diversity of fish populations and various fisheries, yet they are increasingly threatened by anthropogenic stressors, including overfishing, habitat degradation, coastal development, and the cascading effects of climate change. Effective habitat management and restoration are essential but are often missing for flats ecosystems. Despite navigating a landscape of imperfect knowledge for these systems, decisive action and implementation of habitat protection and restoration is currently needed through policy and practice. We present a comprehensive set of 10 strategic guiding principles necessary for integrating habitat management and restoration for the conservation of interconnected flat ecosystems. These principles include calls for comprehensive ecosystem-based ­management, integrating adaptive strategies that leverage diverse partnerships, scientific research, legislative initiatives, and local and traditional ecological knowledge. Drawing on successes in other environmental management realms, we emphasize the importance of evidence-informed approaches to address the complexities and uncertainties of flats ecosystems. These guiding principles aim to advance flats habitat management and restoration, promoting ecological integrity and strengthening the socio-economic resilience of these important marine environments.
Epistasis and cryptic QTL identified using modified bulk segregant analysis of copper resistance in budding yeast
Authors: Buzby Cassandra , Plavskin Yevgeniy , Sartori Federica M O , Tong Qiange , Vail Janessa K , Siegal Mark L
Published: February 2025

The contributions of genetic interactions to natural trait variation are challenging to estimate experimentally, as current approaches for detecting epistasis are often underpowered. Powerful mapping approaches such as bulk segregant analysis, wherein individuals with extreme phenotypes are pooled for genotyping, obscure epistasis by averaging over genotype combinations. To accurately characterize and quantify epistasis underlying natural trait variation, we have engineered strains of the budding yeast Saccharomyces cerevisiae to enable crosses where one parent’s chromosome is fixed while the rest of the chromosomes segregate. These crosses allow us to use bulk segregant analysis to identify quantitative trait loci (QTL) whose effects depend on alleles on the fixed parental chromosome, indicating a genetic interaction with that chromosome. Our method, which we term epic-QTL (for epistatic-with-chromosome QTL) analysis, can thus identify interaction loci with high statistical power. Here we perform epic-QTL analysis of copper resistance with chromosome I or VIII fixed in a cross between divergent naturally derived strains. We find seven loci that interact significantly with chromosome VIII and none that interact with chromosome I, the smallest of the 16 budding yeast chromosomes. Each of the seven interactions alters the magnitude, rather than the direction, of an additive QTL effect. We also show that fixation of one source of variation—in this case chromosome VIII, which contains the large-effect QTL mapping to CUP1—increases power to detect the contributions of other loci to trait differences.
Impact of non-significant right coronary ostial involvement on coronary events in type A aortic dissection surgery
Authors: Huang Ling-Chen , Hu Xiang-Min , Zhang Ai-Kai , Shao Ze-Hua , Sun Yang-Xue , Zhao Dong , Chang Yi , Qian Xiang-Yang , Guo Hong-Wei
Published: February 2025

OBJECTIVES

Coronary-related technical complications constantly occur during type A aortic dissection surgical repair and are potentially fatal, yet their risk factors require further investigation. The intricate morphology of coronary ostial involvement may have a substantial impact.

METHODS

From June 2019 to January 2024, consecutive type A aortic dissection patients who underwent open surgery were included. Patients were divided into the coronary involvement group (non-significant involvement: Neri A-dissected intima involving the margin of the coronary ostium; significant involvement: Neri B and Neri C) and the non-involvement group. Coronary events were defined as coronary-related technical complications necessitating bailout coronary revascularization or coronary ostial repair. Logistic regression analysis identified risk factors associated with coronary events. Overall survival was estimated using Kaplan–Meier method and Cox regression analysis.

RESULTS

Of 1,168 patients, 660 patients had coronary involvement, while 508 did not. Coronary events occurred in 58 patients (4.97%), including 53(4.54%) who required bailout coronary revascularization. Patients with coronary involvement had a higher incidence of coronary events (8.18% vs 0.79%, p < 0.001). Logistic regression analysis revealed that significant right coronary involvement was associated with coronary events (odds ratio : 20.58, 95%confidence interval : 7.37–57.50, p < 0.001). Notably, non-significant right coronary involvement, accounting for 44.61% of patients, was also associated with coronary events compared to those without involvement (odds ratio : 7.05, 95%confidence interval : 2.69–18.50, p < 0.001).

CONCLUSIONS

Coronary events occurred in 4.97% patients. Significant right coronary involvement is strongly associated with coronary events; non-significant right coronary involvement, which is relatively common in surgical patients, also poses a substantial risk for coronary events and warrants attention.
Interesting properties of Opuntia’s cladodes: an updated review
Authors: Arias Gorman Adriana M , Monzon Celina M , La Cava Enzo L , Sgroppo Sonia C
Published: February 2025

Opuntia, cactus plants native to Mexico, have adapted to arid and semiarid environments through Crassulacean Acid Metabolism. With over 150 species, they’re found across the Americas, Africa, Australia, India, and the Mediterranean, prized for water storage and ecological implications. Rich in bioactive compounds, Opuntia are gaining attention in nutrition, phytochemistry and technological uses. This review updates knowledge on Opuntia cladodes, explores novel uses like vegetable coatings, evaluates how preservation and cooking impact nutrition, and delves into consumer preferences. Opuntia is common in Mexican and global cuisine, with potential as edible coatings. Opuntia-derived biopolymer films reduce plastic dependency, are eco-friendly, and have varied applications. Research on mucilage’s antimicrobial properties and alternative uses is ongoing. Opuntia’s underutilized status presents numerous opportunities for innovation across food, pharmaceutical, cosmetic, and material science sectors, with potential benefits including climate resilience and economic empowerment of communities. Continuous research aims to fully exploit their potential for societal and environmental benefit.
Halophilic archaea produce wax esters and use an alternative fatty acyl-CoA reductase for precursor synthesis
Authors: Grossi Vincent , Cuny Philippe , Militon Cécile , Witwinowski Jerzy , Eddhif Balkis , Sylvi Léa , Nowakowski Mireille , Kosta Artemis , Antheaume Ingrid , Cornil Johan , Dubrac Sarah , Kende Julia , Gribaldo Simonetta , Borrel Guillaume
Published: February 2025

Wax esters are fatty acid-based neutral lipids thought to be restricted to bacteria and eukaryotes that play a key role in the functioning and maintenance of cells, especially under adverse conditions. Here we show that several halophilic archaea (Halobacteriales) carry a homologue of the bacterial wax synthase gene. Wax ester synthesis and accumulation is demonstrated in one of these (poly)extremophilic archaea, Natronomonas pharaonis, during growth on long-chain fatty acids. Our bioinformatic analysis also shows that the synthesis of fatty alcohols required for wax ester synthesis could be performed by an enzyme evolutionarily related to class I 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR, classically involved in isoprenoid biosynthesis). Using heterologous expression and enzymatic assays, we show that this HMGR homolog, which we named FcrA (for fatty acyl-CoA reductase), reduces fatty acyl-CoA to fatty alcohol, but cannot reduce 3-hydroxy-3-methylglutaryl-CoA to mevalonate. The conservation of HMGR catalytic residues in FcrA suggests that the two enzymes have a similar catalytic mechanism, whereas an elongated substrate-binding pocket and distinct residues may explain FcrA’s selectivity for long chain fatty acyl-CoA. In addition to archaea, FcrA is present in a wide range of bacteria, including ~25% of those predicted to produce wax esters, and accounts for a large proportion of the fatty acyl-CoA reductases found in various environments. Challenging the long-held paradigm that archaea cannot biosynthesize fatty acid-based neutral lipids de novo, this study lays the foundations for further physiological, ecological, and biotechnological investigation of neutral lipid production by systems markedly different from those of eukaryotes and bacteria.
Global perspectives on patient-centered outcomes: advancing patient-centered cancer clinical trials globally
Authors: Monge Cecilia , Eldridge Linsey , Pearlman Paul C , Venkatesh Viji , Tregear Michelle , Loehrer Patrick J , Galassi Annette , Gopal Satish , Ginsburg Ophira
Published: February 2025

Patient-centered clinical trials prioritize the patient experience and outcomes that matter most to those affected by cancer. By centering on patient values and experiences, patient-centered outcomes research generates evidence to inform policies and practices, facilitating more personalized and effective cancer care. This manuscript explores the importance of patient-centered approaches in the global context, emphasizing challenges and opportunities for substantive patient engagement and the integration of patient-reported measures in clinical therapeutic trials in low- and middle-income countries. Despite important barriers such as limited infrastructure and funding constraints, leveraging innovative strategies and investing in research infrastructure and regulatory harmonization initiatives can enhance the capacity of low- and middle-income countries to conduct high-quality research and address the global burden of cancer more effectively. Through these efforts, patient-centered care and research can be extended to underserved populations, ensuring equitable access to cancer care worldwide.
The fundamentals of multiplicity adjustment in biostatistics
Authors: Izmirlian Grant , Sirota Lev A , Berger Vance W , Kipnis Victor
Published: February 2025

The statistical problem of multiplicity is concerned with making protected multiple inferences and their valid interpretation in a particular study. Most discussions of multiplicity focus on the increase of type I error rate if testing is done without any adjustment, with only a few papers discussing its ramifications for type II errors/power. We provide a survey of main approaches to protected inference in biomedical studies, touching on procedures to control the family-wise error rate, false discovery rate, as well as false discovery exceedance probability. We discuss several notions of power including total power, average power, and power defined as exceedance probability for the true positive proportion. We provide commentary on best practices for adjusting for multiplicity in both type I and type II errors within families defined by primary, secondary, and exploratory endpoints in clinical trials and in experimental studies.
Resisting dehumanisation – Exploring nonideal human rights education
Authors: Kasa Tuija , Leiviskä Anniina
Published: February 2025

Human rights and human rights education (HRE) have been criticized for being too ideal and decontextualized. Current critical HRE discussion emphasizes the political contestation of rights, and is suspicious of universals. Many such criticisms provide important insights for revising HRE. However, in this article, we argue that the denial of universality and normativity regarding the philosophical grounding of HRE is somewhat unjustified, and leads to moral and philosophical problems. Therefore, we seek to renew the theoretical foundations of HRE through the approach of nonideal theorizing. Drawing on the works of the previously neglected Judith Shklar and other nonideal theorists in the context of HRE, we construct a nonideal universalism founded on a negative moral conception of dehumanization. We argue that approaching human rights violations from the perspective of dehumanization offers theoretical renewal to the current discussion on human rights, and a basis for nonideal HRE. This is a new angle in the current critical HRE discussion because it takes the prevailing criticisms of human rights and HRE seriously but does not deny the non-negotiable, universal moral core of human rights. We argue that such a core is necessary for making sense of the moral responsibilities related to HRE and for transcending given contexts. We emphasize the importance of this moral approach for HRE and suggest that nonideal HRE can foster a sensitivity to injustice through political and moral imagination against actual cases of dehumanization. Additionally, nonideal HRE has the potential to disturb passive injustice and foster moral sensibility through education.
A note on applying the Syuzhet program to film dialogue
Authors: Salt Barry
Published: February 2025

The Syuzhet program is tested in two particular cases, and produces highly questionable results.
Thermal equilibration in collisionless magnetospheric plasmas via entropy-mode turbulence
Authors: Numata Ryusuke
Published: February 2025

A planetary magnetosphere is a peculiar plasma environment where a high-temperature plasma is confined in a strongly inhomogeneous dipolar magnetic field generated by a planet. Turbulence driven by the magnetic curvature and density gradient (the entropy mode) is known to cause the inward pinch whereby particles are transported against the density gradient to achieve high confinement. However, a comprehensive understanding of how the global magnetospheric plasma confinement is determined is still missing. Here, we show that the entropy-mode turbulence equilibrates temperatures between species without collisions in a magnetospheric plasma. The classical stability analysis in terms of energetic consideration reveals the interchangeable roles of electrons and ions for destabilization due to resonance with drift waves depending on their temperature. One of the species has negative energy and grows its energy fed from the background density gradient. Turbulence driven by the microscopic (kinetic) instability tends to rearrange the internal energy between species, pre-dominantly via linear physics, leading to an equal temperature state. Our new finding adds an ingredient to energy transport processes and contributes to a consistent explanation of the global self-organization of magnetospheric plasmas.