bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating Harms Associated With Prolonged Antibiotic Duration of Therapy in Community-Dwelling Older Adults: A Cohort Study Using Instrumental Variable Analysis
Authors: Langford Bradley J , Brown Kevin A , Lau Cindy , Calzavara Andrew , Krueger Carsten , Leung Valerie , Daneman Nick , Schwartz Kevin L
Published: December 2024

Background

Shorter courses of antibiotic therapy are increasingly recommended to reduce antibiotic exposure. However, quantifying the real-world impact of duration of therapy is hindered by bias common in observational studies. We aimed to evaluate the harms and benefits of longer versus shorter duration of therapy in older adults.

Methods

This was a population-based cohort study using administrative health data from Ontario, Canada. We included outpatients aged 66–110 years who received a prescription for amoxicillin, cephalexin, and/or ciprofloxacin. Prescriptions were categorized as short (3–7 days) or long (8–14 days) duration. The primary outcome was a composite of antibiotic-related harms, including adverse reactions, Clostridioides difficile infection, and antibiotic resistance. The secondary outcome was a composite of safety measures including repeat antibiotic prescriptions, hospital visits, and mortality. To reduce risk of bias, we used an instrumental variable analysis where the instrument was prescriber proportion of antibiotics that were long duration.

Results

Among 117 682 eligible patients, there was no difference in the primary harms outcome for patients receiving longer versus shorter courses of antibiotics (adjusted odds ratio and 95% confidence interval [CI]): amoxicillin, 0.99 (.84–1.15); cephalexin, 1.11 (.90–1.38); ciprofloxacin, 0.94 (.74–1.20). Secondary safety outcomes were similar, with longer compared to shorter courses of antibiotic therapy (odds ratio and 95% CI): amoxicillin, 1.01 (.94–1.08); cephalexin, 1.06 (.97–1.17); ciprofloxacin, 0.99 (.85–1.15).

Conclusions

In this instrumental variable analysis of community-dwelling older adults, longer antibiotic courses were not associated with an increased benefit or harm compared to shorter courses.
Performance of Noninvasive Tests for Metabolic Dysfunction-Associated Steatohepatitis and Liver Fibrosis Resolution after Bariatric Surgery
Authors: Angelini Giulia , Panunzi Simona , Pompili Maurizio , Riccardi Laura , Garcovich Matteo , Verrastro Ornella , Russo Sara , Mare Tracey , Luxton James , le Roux Carel W , Raffaelli Marco , Mingrone Geltrude , Vincent Royce P
Published: December 2024

Background

Noninvasive tests (NITs) to monitor metabolic dysfunction-associated steatohepatitis (MASH) progression and response to interventions are needed because of the risks of liver biopsy. A monocytes-based diagnostic test using perilipin-2 (PLIN2) and Ras-related protein-14 (RAB14) predict the severity of MASH and fibrosis. Here we compared the performances of PLIN2 and RAB14 with cytokeratin-18 (CK18) assessed by Ella™ or M65 ELISA in predicting MASH and fibrosis resolution following bariatric surgery in a longitudinal and histologically characterized cohort of individuals with obesity.

Methods

Participants in the BRAVES randomized controlled trial underwent ultrasound-guided needle liver biopsy at baseline and 1 year after surgery. We evaluated NITs’ performance using area under the receiver operating characteristic and calculated accuracy, sensitivity, and specificity based on the Youden threshold. Univariable and multivariable logistic models were used to assess the role of recorded covariates in predicting MASH and fibrosis severity, as well as resolution or improvement.

Results

After surgery, patients who experienced MASH improvement or resolution showed a significant decrease in PLIN2 expression as compared to those who did not, while patients with fibrosis improvement displayed an increase in RAB14. No differences were found for CK18. The diagnostic accuracy of PLIN2 and RAB14 for the prediction of MASH resolution or fibrosis improvement was superior to CK18 assessed by either Ella or M65 ELISA.

Conclusions

PLIN2 and RAB14, but not CK18, are markers for monitoring improvements in MASH and fibrosis after interventions such as bariatric surgery. This may reduce or eliminate the need for frequent liver biopsies.

ClinicalTrials.gov Registration Number: NCT03524365
Brainstem C1 neurons mediate heart failure decompensation and mortality during acute salt loading
Authors: Schwarz Karla G , Pereyra Katherin V , Díaz-Jara Esteban , Vicencio Sinay C , Del Rio Rodrigo
Published: December 2024

Aims

Heart failure (HF) is an emerging epidemic worldwide. Despite advances in treatment, the morbidity and mortality rate of HF remain high, and the global prevalence continues to rise. Common clinical features of HF include cardiac sympathoexcitation, disordered breathing, and kidney dysfunction; kidney dysfunction strongly contributes to sodium retention and fluid overload, leading to poor outcomes of HF patients. We have previously shown that brainstem pre-sympathetic neurons (C1) from the rostral ventrolateral medulla (RVLM) play a key role in sympathetic regulation in experimental models of HF. However, the role of RVLM-C1 neurons during salt-loading in the context of HF is unknown. This study tests whether RVLM C1 neurons drive cardiorespiratory decompensation and ultimately lead to sudden death in HF rats.

Methods and results

Adult male Sprague–Dawley rats underwent arteriovenous shunt to induce HF with preserved ejection fraction (HFpEF). Two weeks after HFpEF induction, bilateral selective ablation of RVLM C1 neurons was performed using anti-dopamine β-hydroxylase-saporin toxin. Animals were then fed a high Na+ diet (3% Na+ in food and 2% Na+ in water) for 3 weeks to induce compensated-to-decompensated HF state transition. Echocardiography, cardiac autonomic function, breathing function, and survival were assessed during the progression of HF. Salt loading resulted in marked decompensation in HF rats, as evidenced by a significant decrease in survival rates (survival: 10% vs. 100% HFpEF + Na+ vs. HFpEF). Furthermore, HFpEF + Na+ animals showed a further increase in cardiac sympathetic drive and more severe disordered breathing, including higher hypoxia-related epochs (i.e. apnoeas/hypopnoeas), compared with HF. Ablation of RVLM C1 neurons partly reduced the excessive cardiac sympathoexcitation during salt loading in HF, improved the exaggerated disordered breathing in HFpEF+ Na+ rats, and reduced decompensation-linked mortality. We found that hypoxia, but not high sodium, was the major contributor to impaired calcium handling in isolated adult cardiomyocytes.

Conclusion

Our results strongly suggest that RVLM C1 neurons contribute to acute HF decompensation during salt loading by a mechanism encompassing further increases in sympathetic outflow and hypoxia-related breathing disorders. This mechanism may ultimately impact cardiac contractility through cardiomyocyte calcium mishandling, increasing morbidity and mortality.
No evidence of quantitative honest signaling in aposematic traits of the green and black dendrobatid frog Dendrobates auratus in Costa Rica
Authors: Porras-Brenes Katherine , Church Gabriella , Saporito Ralph A
Published: December 2024

Aposematism is an antipredator strategy in which conspicuous coloration acts as a warning of chemical defenses to potential predators. Evidence suggests that aposematism largely functions under positive frequency-dependent selection, which is thought to maintain uniformity of aposematic signals. Many studies of aposematic organisms have found evidence that color signals and defenses are positively correlated, indicating a quantitatively honest aposematic signal. Dendrobatid poison frogs represent a well-studied group of aposematic organisms that in addition to exhibiting a diversity of color signals also display unique defensive behaviors. Few studies have examined if both behavior and coloration act as quantitative honest signals of alkaloid defenses in poison frogs. We aimed to determine if coloration and behavior are quantitatively honest signals in the green and black poison frog (Dendrobates auratus) among 6 populations from Costa Rica. We (1) evaluated antipredator displays by using behavioral assays in the field, (2) assessed frog conspicuousness and pattern using digital images, and (3) quantified alkaloid profiles from frog skin secretions. We found that Pacific populations are less conspicuous in coloration, had greater quantities of alkaloids, and more frequently performed body-raising defensive behaviors when compared with Caribbean populations. Our results do not support the hypothesis that aposematic traits in D. auratus are quantitatively honest. Rather, our results suggest that phenotypic differences among populations may represent different phenotypic optima for advertising unprofitability to predators based on local environmental conditions, leading to the diversification of aposematic signals in this species.
Duodromic atrioventricular reentry tachycardia: a case report of a rare adenosine insensitive supraventricular tachycardia
Authors: Jacinto Sofia , Figueiredo Margarida , Almeida Inês , Valente Bruno , Oliveira Mário Martins
Published: December 2024

Background

Accessory pathways (AP) are associated with an increased risk of atrioventricular reentry tachycardia (AVRT), presenting as a wide QRS tachycardia if the mechanism is antidromic. Rarely, AVRT may not respond to adenosine, suggesting a duodromic mechanism if the patient has multiple APs. Herein, we present a case of a male patient with multiple APs, wide QRS complex tachycardia, and resistance to adenosine.

Case presentation

A 45-year-old man with Wolff–Parkinson–White (WPW) syndrome was referred for AP ablation. He had previously been admitted with persistent palpitations and wide QRS tachycardia, which was resistant to adenosine. Electrophysiologic study revealed both right lateral and left lateral APs. Ablation successfully eliminated conduction through both pathways. Six months later, the patient remained asymptomatic but exhibited recurrence of pre-excitation on electrocardiogram, suggesting the presence of a third AP. A repeat electrophysiology study confirmed a posteroseptal AP, which was successfully ablated. The patient remained free of pre-excitation at follow-up.

Discussion

This case highlights the complexity of the diagnosis and treatment of wide QRS tachycardias in a patient with WPW. In this case, the failure to respond to adenosine was attributed to the use of a second AP as the retrograde limb of the AVRT circuit, a rare phenomenon known as duodromic AVRT. Successful identification and ablation of all APs was crucial in preventing recurrent arrhythmias, and rare mechanisms such as duodromic tachycardia should be considered when standard treatments fail.
Predictors and outcomes in patients undergoing surgery for acute type A aortic dissection requiring concomitant venoarterial extracorporeal membrane oxygenation support—a retrospective multicentre cohort study
Authors: Pitts Leonard , Gasser Simone , Uzdenov Murat , Gaisendrees Christopher , Bartkevics Maris , Kreibich Maximilian , Luehr Maximilian , Kempfert Jörg , Schoenhoff Florian , Falk Volkmar , Dumfarth Julia
Published: December 2024

OBJECTIVES

The study’s aim was to investigate the outcomes and risk factors for mortality in patients undergoing surgery for acute type A aortic dissection receiving concomitant venoarterial extracorporeal membrane oxygenation (ECMO) support.

METHODS

Patients from 5 European centre who underwent surgery for acute type A aortic dissection and received perioperative venoarterial ECMO support were included. A multivariable binary logistic regression analysis was performed to identify risk factors for 30-day mortality. A receiver operating characteristic curve and restricted cubic splines were designed to investigate the association between pre-ECMO lactate peak and survival.

RESULTS

The final cohort comprised 117 patients. Mean time on ECMO support was 3 days (interquartile range 1–7). In 36 patients (31%), successful ECMO weaning was achieved. Thirty-day mortality was 72%, leading cause for early mortality was multiorgan failure (39%). In total, 20% of patients were discharged from hospital. Pre-ECMO lactate peak [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.005–1.032], presence of preoperative shock (OR 9.47, 95% CI 1.749–98.257) and need for total arch replacement (OR 6.628, 95% CI 1.492–33.373) were identified as associates for 30-day mortality. For pre-ECMO lactate peak, the area under the curve showed an acceptable value of 0.73 and restricted cubic splines showed a significant correlation to survival (P = 0.004) with an increased risk above a lactate level of 85 mg/dl.

CONCLUSIONS

Venoarterial ECMO support may not be futile but should be well balanced against the high-risk profile in this patient cohort. The pre-ECMO lactate peak is an independent risk factor and a valid predictor of 30-day mortality.
A Historiography of Amnesia: Beyond Data, Big Tech and the (Re)Turn to Human Rights
Authors: Dao André
Published: December 2024

According to Elizabeth Renieris’ Beyond Data, contemporary technology governance has become too data-centric. Renieris argues that technology governance must move beyond a narrow focus on ‘data’ and towards a focus on ‘people’. More precisely, she calls for a ‘return to the original human rights-based conceptualisations of privacy and data protection’. Reading Renieris’ argument as symptomatic of a wider tendency, I argue in this review essay that the turn to human rights in technology scholarship is structured by a crucial forgetting or what I call a ‘historiography of amnesia’. While this historiography makes available the argument that human rights can serve as the uncontested normative ground for technology governance, it also obscures the large body of critical human rights scholarship, such that the turn to human rights in Beyond Data is actually a turn to a nostalgic fantasy of an ahistorical, apolitical human rights past.
Sex-specific risk factors for new-onset heart failure: the PREVEND study at 25 years
Authors: van Essen Bart J , Emmens Johanna E , Tromp Jasper , Ouwerkerk Wouter , Smit Marcelle D , Geluk Christiane A , Baumhove Lukas , Suthahar Navin , Gansevoort Ron T , Bakker Stephan J L , Damman Kevin , van der Meer Peter , de Boer Rudolf A , van Veldhuisen Dirk J , Voors Adriaan A
Published: December 2024

Background and Aims

Current estimates for the lifetime risk to develop heart failure with either a reduced (HFrEF) or preserved ejection fraction (HFpEF) and their associated risk factors are derived from two studies from the USA. The sex-specific lifetime risk and population attributable fraction of potentially modifiable risk factors for incident HFpEF and HFrEF are described in a large European community-based cohort with 25 years of follow-up.

Methods

A total of 8558 participants from the PREVEND cohort were studied at baseline from 1997 onwards and followed until 2022 for cases of new-onset HFrEF (ejection fraction < 50%) and HFpEF (ejection fraction ≥ 50%) by assessment of hospital records.

Results

A total of 804 cases of new-onset HF were identified (534 HFrEF and 270 HFpEF) during 25 years of follow-up. The mean age at baseline was 50 years for men and 47 years for women. The mean age at onset of HF was 72.1 years in men and 74.2 years in women. The overall lifetime risk of developing HF was 24.5% in men compared to 23.3% in women. The lifetime risk of HFrEF was lower in women compared with men (11.9% vs. 18.1%), while the lifetime risk of HFpEF was higher in women compared with men (11.5% vs. 6.4%). In women, 71% of incident HFrEF cases were attributable to eight risk factors (hypertension, hypercholesterolaemia, obesity, smoking, atrial fibrillation, chronic kidney disease, myocardial infarction, and diabetes mellitus) and 60% in men. In women, 64% of incident HFpEF cases were attributable to those risk factors, whereas this was 46% in men. More specifically, in both men and women, hypertension and hypercholesterolaemia were the strongest risk factors for HFrEF, whereas hypertension and obesity were the strongest risk factors for HFpEF.

Conclusions

In this European cohort, the lifetime risk of developing HFrEF was greater in men than in women, while women were at greater risk of developing HFpEF. Eight directly and indirectly modifiable risk factors substantially accounted for the risk of developing HFrEF and HFpEF, particularly in women.
Hospitalized upper extremity artery disease patients: treatment and long-term outcomes
Authors: Makowski Lena , Engelbertz Christiane , Köppe Jeanette , Dröge Patrik , Ruhnke Thomas , Günster Christian , Gerß Joachim , Freisinger Eva , Malyar Nasser , Reinecke Holger , Feld Jannik
Published: December 2024

Background and Aims

Current knowledge about upper extremity artery disease (UEAD) is scarce. This study aimed to evaluate the prevalence, treatment patterns, and short- and long-term outcomes of patients suffering from UEAD.

Methods

Retrospective health claims data of patients who were hospitalized with a primary diagnosis of UEAD between 2010 and 2017 were analysed. The data were obtained from 11 legally independent statutory health insurance funds of the ‘AOK-Die Gesundheitskasse’. Risk factors, comorbidities, pharmacotherapy, revascularization procedure, and outcome were evaluated with a particular focus on sex-related disparities (median follow-up time: 5.5 years).

Results

Among 2437 UEAD patients (43% female, median age of 67 years), 80% were solely atherosclerotic (UEADa), while 20% had concomitant inflammatory/connective tissue diseases (UEADc/i). Cardiovascular risk factors and comorbidities were highly prevalent in both sexes. Coronary, cerebrovascular, and lower extremity artery diseases and organ failure such as chronic kidney and heart failure were more frequent in men compared with women. At index stay, women had higher rate of revascularization than men (37% vs. 27%). The 5 year mortality among the entire population was almost 50%, even higher in men (UEADa: 51% vs. 36% P < .001; UEADc/i: 44% vs. 36%, P < .05). Furthermore, men had higher rates of upper limb amputation compared with women despite equal secondary preventive pharmacotherapy (UEADa: 26% vs. 11%, P < .001; UEADc/i: 30% vs. 18%, P < .01).

Conclusions

Upper extremity artery disease patients, irrespective of the underlying disease type, face a poor prognosis with elevated proportion of amputation and mortality. Male sex was linked to increased risk of future cardiovascular and limb events including death. Further investigation is warranted to understand the underlying causes of the sex-related disparities and identify treatment improvements.
Public Perceptions of Women Peacekeepers in Troop Contributing Countries
Authors: Huber Laura
Published: December 2024

A belief that women's representation increases legitimacy informs United Nations peacekeeping policies and the foreign policy agendas of many states. However, we do not know how women's participation alters support for UN peacekeeping within troop contributing countries. Based on gender stereotypes, the public may assume that women peacekeepers indicate that peacekeeping missions are more legitimate, which may increase support. Yet, if women peacekeepers are harmed, this may decrease support due to the gendered protection norm. Moreover, exposure to women peacekeepers may challenge gender roles. Using survey experiments in India and South Africa, this study finds that women peacekeepers’ deployment or death does not impact support for peacekeeping. However, exposure to women's casualties increases support for women's rights to some extent. Further, a survey of representatives of the UN Special Committee on Peacekeeping Operations reveals gaps between decision-makers’ beliefs about how women peacekeepers impact public support and the experimental findings.
Adaptation in the Alleyways: Candidate Genes Under Potential Selection in Urban Coyotes
Authors: Kreling Samantha E S , Vance Summer E , Carlen Elizabeth J
Published: December 2024

In the context of evolutionary time, cities are an extremely recent development. Although our understanding of how urbanization alters ecosystems is well developed, empirical work examining the consequences of urbanization on adaptive evolution remains limited. To facilitate future work, we offer candidate genes for one of the most prominent urban carnivores across North America. The coyote (Canis latrans) is a highly adaptable carnivore distributed throughout urban and nonurban regions in North America. As such, the coyote can serve as a blueprint for understanding the various pathways by which urbanization can influence the genomes of wildlife via comparisons along urban–rural gradients, as well as between metropolitan areas. Given the close evolutionary relationship between coyotes and domestic dogs, we leverage the well-annotated dog genome and highly conserved mammalian genes from model species to outline how urbanization may alter coyote genotypes and shape coyote phenotypes. We identify variables that may alter selection pressure for urban coyotes and offer suggestions of candidate genes to explore. Specifically, we focus on pathways related to diet, health, behavior, cognition, and reproduction. In a rapidly urbanizing world, understanding how species cope and adapt to anthropogenic change can facilitate the persistence of, and coexistence with, these species.
Characterizing Cognitive Dispersion and its Correlates Across the Adult Lifespan in MIDUS
Authors: Klepacz Laura M , Cerino Eric S , Hamm Jeremy M
Published: December 2024

Objectives

Although research has shown that higher levels of within-person variability across cognitive tasks (dispersion) are associated with cognitive decline in clinical samples, little is known about dispersion in comparatively younger, non-clinical, and national samples. A better understanding of dispersion is needed to elucidate for whom and under what circumstances dispersion can be used as a reliable indicator of cognitive health.

Method

We used data from the Midlife in the United States Study (MIDUS; n = 2,229; Mage = 56 years, range = 33-83; 56% female) to: (a) characterize dispersion and its cross-sectional correlates in a non-clinical, adult lifespan sample and (b) examine changes in dispersion over time to determine for whom changes in dispersion may reflect better or worse cognitive aging.

Results

Correlations showed higher levels of dispersion were associated with higher levels of mean performance at both waves (rs = .28-.29). Autoregressive main effect models showed that increases in dispersion were associated with less decline in mean performance over the two-wave, 9-year follow-up period (β = .17, p < .001). Moderation models showed that the link between change in dispersion and change in mean performance was pronounced in comparatively older adults (β = .28), women (β = .27), individuals with less education (β = .23), and those with lower income (β = .23) (all ps < .001).

Discussion

Findings suggest that increases in dispersion may not always be maladaptive in normative, adult lifespan samples and may reflect healthier cognitive profiles in individuals who are at greater risk for cognitive impairment.
The Effects of Risky Behaviors and Social Factors on the Frequency of Fraud Victimization Among Known Victims
Authors: DeLiema Marguerite , Gao Siyu , Brannock Daniel , Langton Lynn
Published: December 2024

Background and Objectives

Routine activity theory (RAT) asserts that a suitable target’s exposure to a motivated offender in the absence of capable guardians increases their likelihood of crime victimization. We use these principles to assess the extent to which engaging in risky routine activities—for example, entering sweepstakes drawings, answering unknown calls—is associated with victimization frequency among older adult mass marketing fraud victims across five types of scams: investment fraud, sweepstakes and lottery fraud, romance and family/friend imposter scams, fake products and services, and charity scams. We also examine whether financial and social vulnerability characteristics (loneliness, preference for taking financial risks, financial fragility) are associated with victimization frequency in older adults.

Research Design and Methods

A survey was administered to households that the U.S. Postal Inspection Service identified as having recently responded to one or more mail scam solicitations. Respondents answered questions on their behaviors, financial risk preferences, social and demographic characteristics, and number of past-year victimization experiences with 5 types of fraud.

Results

As predicted based on RAT, routine activities that increase a target’s exposure to motivated offenders are positively associated with fraud victimization frequency, although more frequent online activity was negatively associated with victimization frequency contrary to hypotheses. Precarious financial and emotional states such as financial fragility and loneliness also were associated with greater victimization frequency, and more frequent social engagement and living with others (the presence of capable guardians) had no effect.

Discussion and Implications

Target suitability factors such as loneliness, financial fragility, and risky financial preferences and behaviors are associated with a higher frequency of fraud victimization among older adults. Consumer education should include information on reducing risky behaviors that can increase fraud exposure. More frequent social engagement may not be protective. Older adults who are financially fragile and experiencing loneliness require more safeguards.
The long non-coding RNA MSTRG.32189-PcmiR399b-PcUBC24 module regulates the phosphate accumulation and disease resistance to Botryosphaeria dothidea in pear
Authors: Yang Yuekun , Lv Shamei , Huang Xiaosan , He Ying , Zhang Xiaoyan , Liu Yu , Wang Guoping , Hong Ni , Wang Liping
Published: December 2024

Pear ring rot disease (Botryosphaeria dothidea) causes a significant threat to the healthy development of the pear industry. Recent research has identified the functional role of long noncoding RNAs (lncRNAs) in various biological processes of plants. The role of lncRNAs in pear defense response remains unknown. In this study, transcriptome sequencing was used to analyze long non-coding RNAs in pear stem infected with B. dothidea. It showed that 3,555 lncRNAs were identified, of which 286 lncRNAs were significantly differentially expressed. GO and KEGG analysis showed that cis- and trans-regulated target genes were enriched in multiple disease-resistant related pathways. More specifically, MSTRG.32189 predicted as an endogenous target mimic (eTM) was significantly down-regulated in response to B. dothidea infection, which was confirmed to inhibit the cleavage effect of PcmiR399b on PcUBC24. The transgenic Arabidopsis of OE-MSTRG.32189 exhibited lower Pi content and weaker disease resistance to Botrytis cinerea compared to WT. In pear callus, overexpression of MSTRG.32189 negatively regulated PcmiR399b, which decreased Pi content and reduced disease resistance. Whereas overexpressing PcmiR399b in pear callus exhibited the opposite effects compared with OE-MSTRG.32189. Overexpression and knock-out of PcUBC24 further clarified that PcUBC24 negatively regulate the Pi content and disease resistance to B. dothidea infection. Furthermore, the ROS levels and the expressions of disease resistance pathway-related genes were regulated by the MSTRG.32189-PcmiR399b-PcUBC24 module in transgenic pear callus, which contributed to disease resistance. Overall, our results demonstrated the role of lncRNAs in pear defense response, revealing MSTRG.32189-PcmiR399b-PcUBC24 module regulates phosphate accumulation and disease resistance to B. dothidea infection in pear.
Charting a science course for the sustainable transformation of aquatic food systems
Authors: Agostini Vera N , Olsen Erik , Tiffay Céline , Allison Edward H , Cojocaru Andreea-Laura , Costello Christopher , Darias Maria J , Fabinyi Michael , Fulton Elizabeth A , Gelcich Stefan , Mills Katherine E , Msuya Flower E , Thilsted Shakuntala H , Tigchelaar Michelle
Published: December 2024

Aquatic foods hold a unique potential to contribute to a much-needed transformation of food systems thanks to their high nutritional value, cultural significance, and relatively low environmental impact. However, realizing this potential requires a transformative approach to help overcome two grand challenges: sustainably increasing the production of nutritious aquatic foods and ensuring equitable access to these resources. This paper highlights the key recommendations from the White Paper on Challenge 3 (‘Sustainably nourish the global population’) of the United Nations Decade of Ocean Science for Sustainable Development (hereafter, the Ocean Decade), developed by a group of experts under the Vision 2030 process, on the science needed to support a ‘Blue Transformation’. A holistic, interdisciplinary science agenda is proposed, emphasizing strengthened institutional and public–private partnerships, prioritizing the inclusion of small-scale actors, women, and youth, and focusing on delivering science targeted to solve specific challenges. The Ocean Decade provides a platform to catalyse these efforts, fostering a paradigm shift towards inclusive, co-created science. Achieving these goals will enable aquatic food systems to contribute significantly to global food security and the Sustainable Development Goals by 2030.
Examining the learning curves in robotic cardiac surgery wet lab simulation training
Authors: Atroshchenko Gennady V , Navarra Emiliano , Valdis Matthew , Sandoval Elena , Hashemi Nasseh , Cerny Stepan , Pereda Daniel , Palmen Meindert , Bjerrum Flemming , Bruun Niels Henrik , Tolsgaard Martin G
Published: December 2024

BACKGROUND

Simulation-based training has gained distinction in cardiothoracic surgery as robotic-assisted cardiac procedures evolve. Despite the increasing use of wet lab simulators, the effectiveness of these training methods and skill acquisition rates remain poorly understood.

OBJECTIVES

This study aimed to compare learning curves and assess the robotic cardiac surgical skill acquisition rate for cardiac and noncardiac surgeons who had no robotic experience in a wet lab simulation setting.

METHODS

In this prospective cohort study, participants practiced 3 robotic tasks in a porcine model: left atriotomy closure, internal thoracic artery harvesting and mitral annular suturing. Participants were novice robotic cardiac and noncardiac surgeons alongside experienced robotic cardiac surgeons who established performance benchmarks. Performance was evaluated using the time-based score and modified global evaluative assessment of robotic skills (mGEARS).

RESULTS

The participants were 15 novice surgeons (7 cardiac; 8 noncardiac) and 4 experienced robotic surgeons. Most novices reached mastery in 52 (±22) min for atrial closure, 32 (±18) for internal thoracic artery harvesting and 34 (±12) for mitral stitches, with no significant differences between the cardiac and noncardiac surgeons. However, for mGEARS, noncardiac novices faced more challenges in internal thoracic artery harvesting. The Thurstone learning curve model indicated no significant difference in the learning rates between the groups.

CONCLUSIONS

Wet lab simulation facilitates the rapid acquisition of robotic cardiac surgical skills to expert levels, irrespective of surgeons’ experience in open cardiac surgery. These findings support the use of wet lab simulators for standardized, competency-based training in robotic cardiac surgery.
No virological failure in patients living with HIV with past NNRTI resistance-associated mutations switched to doravirine-containing regimens
Authors: Abdi B , Saliba S , Wirden M , Faycal A , Cocherie T , Palich R , Schneider L , Seang S , Valantin M A , Pourcher V , Calvez V , Marcelin A , Katlama C
Published: December 2024

Background

Doravirine is licensed in patients living with HIV (PWH) harbouring no prior resistance to any NNRTIs. We aimed to evaluate in real life the efficacy of doravirine with prior NNRTI virological failure and NNRTI resistance-associated mutations (RAMs).

Methods

This observational study included PWH switched to a doravirine-containing regimen between 30 September 2019 and 1 May 2022, with an HIV-1 RNA of ≤50 copies/mL and past NNRTI-RAMs. The main outcome was the proportion of participants with virological failure at Week 48 and Week 96. Secondary outcomes evaluated the rate of viral suppression and transient virological blip, RAMs in the case of virological failure and side effects.

Results

A total of 102 patients were analysed, mostly men (63%), with a median age of 59 years (IQR 51–63). The median time since HIV-1 diagnosis was 26 years (IQR 16–31), on ART for 22 years (IQR 14–26) and virally suppressed for 7 years (IQR 1–11).

Of the patients analysed, 25/102 (25%) had documented historical RAMs to doravirine, 9/25 (36%) showing possible resistance and 16/25 (64%) showing major resistance. The resistance profile primarily (21/23) consisted of the K103N, Y181C and/or G190A/E reverse transcriptase substitutions. Median time since the last detection of NNRTI-RAMs was 12 years (5–17). Over 2 years follow-up, no virological failure occurred, neither at Week 48 (0/87; 0%) nor Week 96 (0/86; 0%).

Conclusions

This is the first real-world study to provide new insight about the use of doravirine-containing regimens as a treatment in long-term suppressed patients whose viruses harboured specific NNRTI-RAMs in their history.
Advances in analytical methodologies for detecting novel psychoactive substances: a review
Authors: Krotulski Alex J , Mata Dani C , Smith Christina R , Palmquist-Orlando Kaitlyn B , Modell Celia , Vikingsson Svante , Truver Michael T
Published: December 2024

Novel psychoactive substances (NPSs) have historically been challenging compounds to analyze in forensic toxicology. The identification, detection, and quantitation of these analytes and their metabolites have been difficult due to their rapid emergence, short lifespan, and various potencies. Advancements in analytical instrumentation are fundamental to mitigating these NPS challenges by providing reliable identification and sensitivity. This review discusses the pros and cons of various analytical instruments that have played a pivotal role in NPS analysis. As analytical technology advanced, the ability to analyze for NPS became easier with high-resolution mass spectrometry (HRMS); however, traditional immunoassays are still beneficial for some NPS classes such as benzodiazepines. Over 200 articles from 2010–23 were reviewed, and 180 were utilized for this review. Journal articles were categorized according to the technology used during analysis: immunoassay, gas chromatography–MS, liquid chromatography–MS—low resolution, and liquid chromatography–MS—high resolution to allow for quick references based on a laboratory’s technologies. Journal articles were organized in table format to outline the authors, NPS drug classes, and instrumentation used, among other important information.
Postmortem distribution of mitragynine and 7-hydroxymitragynine in 51 cases
Authors: Osawa Kei A , Johnson Robert D
Published: December 2024

The prevalence of mitragynine (kratom) in forensic toxicology casework has steadily increased over time. Readily available and currently legal, mitragynine is widely used for its stimulant and, depending on concentration, sedative effects. Our laboratory analyzed various fluid and tissue specimens from 51 postmortem cases to investigate the distribution of mitragynine and its active metabolite 7-hydroxymitragynine. Central and peripheral blood concentrations were compared, with an average heart blood to femoral blood ratio being 1.37 for mitragynine and 1.08 for 7-hydroxymitragynine. This ratio >1.0 suggests that mitragynine has some propensity toward postmortem redistribution; however, the difference in concentrations of mitragynine and 7-hydroxymitragynine is not statistically significant. Large average mitragynine to 7-hydroxymitragynine ratios of 30.9 in femoral blood and 32.4 in heart blood were observed compared to average ratios of 14.8 in vitreous humor and 16.9 in urine. In addition, the stability of these two compounds was investigated in both matrix and organic solvent. When stored refrigerated (4°C), mitragynine was stable for up to 30 days and 7-hydroxymitragynine was stable for up to 7 days with an analyte loss of <20%. Following 60 days of refrigerated storage, 7-hydroxymitragynine concentrations dropped over 50% from initial concentrations. Methanolic preparations of mitragynine and 7-hydroxymitragynine were stable following 3 months of storage at −20°C.
Observation of morphological changes in silicon-based negative-electrode active materials during charging/discharging using Operando scanning electron microscopy
Authors: Kurosawa Takako , Fukumoto Noriaki , Inoue Kaoru , Igaki Emiko
Published: December 2024

The direct observation of the morphological changes in silicon-based negative electrode (Si-based negative electrode) materials during battery charging and discharging is useful for handling such materials and in electrode plate design. We developed an operando scanning electron microscopy (operando SEM) technique to quantitatively evaluate the expansion and contraction of Si-based negative electrode materials. A small all-solid-state lithium-ion battery was charged and discharged, and the expansion/contraction of particles while harnessing capacity was observed using SEM. We found that in a silicon monosilicate (SiO)/graphite negative electrode, SiO expanded first during charging, and graphite contracted first during discharging. Our study provides insights into the relationship between capacity and expansion and contraction coefficient of Si-based negative electrode materials.
At All Costs: How Relative Rebel Strength Affects PGM Sexual Violence in Civil Conflict
Authors: Roy Chhandosi , Sarwari Mehwish
Published: December 2024

Does the military strength of rebel movements affect conflict-related sexual violence by pro-government militias (PGMs)? Existing studies on PGMs show the significant role that PGMs can have in shaping conflict dynamics and outcomes. What remains understudied is how the variation in power capabilities between conflict actors and the sources of support for PGMs influences civilian victimization by militia groups. We argue that strong rebels tip the balance of power against the state, making the state more susceptible to authorizing or allowing sexual violence by PGMs. In addition, the level of autonomy of PGMs from the government is likely to influence their sexual violence, conditional on rebel strength. When rebels are militarily strong, states are likely to order or tolerate sexual violence by PGMs that they train and/or provide resources to, thereby resulting in sexual violence by state-dependent PGMs. Examining all civil conflicts from 1989 to 2009 and using newly collected data on state-dependence of PGMs, our empirical findings provide evidence that PGMs are associated with higher levels of conflict-related sexual violence when the government faces strong rebels. Results also show that the likelihood of sexual violence by state-dependent PGMs increases when rebels exhibit strong military capabilities.
Unequal refugeeness. Race, gender, and co-belligerence from Poles in colonial Africa to Ukrainians in Poland
Authors: Lingelbach Jochen
Published: December 2024

Refugee-receiving states do not live up to the universalist ideals of international refugee legislation but are selective and discriminatory. The case of Poland’s acceptance of Ukrainians while simultaneously building a border wall to keep out non-Ukrainians is an obvious case. Based on historical research on the British Empire’s policies towards European refugees, this article looks into a comparable moment when governments made an exception to their established anti-refugee policy and accepted certain groups of refugees. The British colonial administration in East Africa rejected Jewish refugees but accepted a specific group of Poles during the Second World War. This exception under war conditions was legitimized with an emphasis on the group’s gender, race, and connection to the co-belligerent Polish army. They were the white women and children of the Polish male soldiers fighting with the British against the Axis. The recent welcome for Ukrainian refugees in Poland followed similar lines of argumentation.
Technique for areolar reduction areolar-sparing mastectomy
Authors: Lawrence Zachary , Stroman Joel C , Karu Heather
Published: December 2024

Achieving satisfactory nipple esthetics following skin-sparing or nipple-sparing mastectomy is an important element of ensuring positive patient outcomes. Several techniques used to reconstruct the nipple–areolar complex have been described in previous literature and have had success in securing good cosmetic outcomes. For patients with macrothelia, surgeons may employ a number of options in reducing nipple size. Existing studies have shown common preferences among individuals surveyed regarding breast cosmesis, specifically related to the nipples and areolae. However, for individuals with disproportionately large areolae following areolar-sparing mastectomy, there is scant literature to suggest methods of reducing the size of the areolae, and current practice appears to be based upon fixed diameters of areolar sizers. In this technical report, we describe a suture-only technique that successfully reduced areola diameter and recreated the appearance of a nipple with a small central projection following areolar-sparing mastectomy.
Sexual function and related predictors in male with multiple sclerosis and neuromyelitis optica spectrum disorder: a case–control study
Authors: Vaheb Saeed , Yazdan Panah Mohammad , Mohammadi Mohammad , Sadri Mohammad Amin , Ebrahimi Narges , Loghmani Sarina , Beigi Marjan , Shaygannejad Vahid , Mirmosayyeb Omid
Published: December 2024

Background

Sexual dysfunction (SF) is a prevalent and distressing comorbidity in males with multiple sclerosis (MwMS) and neuromyelitis optica spectrum disorder (MwNMOSD).

Aims

This study aimed to assess the SF in MwMS and MwNMOSD in comparison to male healthy controls (HCs) and identify its associated predictors.

Methods

This case–control study was conducted from February 2023 to January 2024 at the MS clinic of Kashani Hospital, Isfahan, Iran. Participants included 49 MwMS, 27 MwNMOSD, and 40 HCs. Demographic, clinical, and psychological data were collected, and SF was evaluated by the International Index of Erectile Function (IIEF). Linear regression was used to assess relationships between variables.

Outcomes

SF was significantly worse in the MwMS and MwNMOSD compared to the HCs.

Results

SF was significantly lower in MwMS and MwNMOSD compared to HCs. In MwMS, significant independent predictors of SF included partner’s education (B = -2.7, P = .003), anxiety (B = -0.6, P = .003), and depression (B = -0.3, P = .026). In MwNMOSD, significant independent predictors of SF were EDSS (B = -5.7, P = .007) and anxiety (B = -1, P = .002).

Clinical Implications

Controlling risk factors such as depression and anxiety can improve SF of MwMS to a significant extent.

Strengths and Limitations

Despite limitations like the cross-sectional design and exclusion of certain variables, our study identifies significant associations between sexual dysfunction and various risk factors in MwMS and MwNMOSD, emphasizing the need for future longitudinal research.

Conclusion

MwMS and MwNMOSD exhibited worse SF than HCs. Multiple factors have been identified as independent predictors of SF within these patient groups.
Contemporary prostate cancer radiation therapy trials may underestimate the risk of biochemical recurrence
Authors: West Michael , Flores Jose M , Mulhall John P
Published: December 2024

Background

Radiotherapy is often given with androgen deprivation therapy for prostate cancer which causes a reduction in testosterone levels, which when below castrate levels, can cause the prostate specific antigen (PSA) levels to be artificially low.

Aim

To determine if high-level radiotherapy clinical trials are underestimating biochemical recurrence (BCR) rates due to inadequate measurement of testosterone levels.

Methods

The study plans for clinical trials performed by the Radiation Therapy Oncology Group (RTOG [now NRG]) on clinicaltrials.gov were reviewed for details on testosterone measurement in trials from 1994 to 2023, namely if the testosterone levels were indexed to PSA levels.

Outcomes

PSA being indexed to testosterone levels and other metrics of testosterone measurement, including time of day of measurement, assay used, and mean testosterone measurement.

Results

Five of 21 (24%) trials stipulated that testosterone levels should be indexed to PSA levels. Eleven of 21 (52%) trials made no mention of testosterone. No trial reported testosterone assay or time of day of measurement. Thirteen of 21 (62%) trials did not require regular follow-up testosterone measurements.

Clinical Implications

The number of clinical trials indexing or regularly measuring testosterone was surprisingly low, which could cause an underestimation of BCR rates.

Strengths and Limitations

Strengths include being the first study, to our knowledge, to analyze the details of testosterone measurement in high-level radiotherapy trials. Limitations include only analyzing RTOG/NRG trials, analyzing unpublished data, and using clinicaltrials.gov rather than official trial protocols to determine details of testosterone measurement.

Conclusion

Indexing of testosterone levels to PSA levels in high-level radiotherapy trials using androgen deprivation therapy was uncommon, possibly rendering data on BCR unreliable, potentially underestimating BCR rates.
Evolutionary Dynamics of RuBisCO: Emergence of the Small Subunit and its Impact Through Time
Authors: Amritkar Kaustubh , Cuevas-Zuviría Bruno , Kaçar Betül
Published: December 2024

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is an ancient protein critical for CO2-fixation and global biogeochemistry. Form-I RuBisCO complexes uniquely harbor small subunits that form a hexadecameric complex together with their large subunits. The small subunit protein is thought to have significantly contributed to RuBisCO's response to the atmospheric rise of O2 ∼2.5 billion years ago, marking a pivotal point in the enzyme's evolutionary history. Here, we performed a comprehensive evolutionary analysis of extant and ancestral RuBisCO sequences and structures to explore the impact of the small subunit's earliest integration on the molecular dynamics of the overall complex. Our simulations suggest that the small subunit restricted the conformational flexibility of the large subunit early in its history, impacting the evolutionary trajectory of the Form-I RuBisCO complex. Molecular dynamics investigations of CO2 and O2 gas distribution around predicted ancient RuBisCO complexes suggest that a proposed “CO2-reservoir” role for the small subunit is not conserved throughout the enzyme's evolutionary history. The evolutionary and biophysical response of RuBisCO to changing atmospheric conditions on ancient Earth showcase multi-level and trackable responses of enzymes to environmental shifts over long timescales.