bluuebunny/crossref_metadata_2025 huggingface dataset:
How do large scale population studies inform vaccine evaluations in England?
Authors: Kirsebom Freja , Hall Victoria , Stowe Julia
Published: February 2025

Large scale population studies are important to monitor and evaluate aspects of a vaccination programme including vaccine coverage, real-world effectiveness, and post-licensure vaccine safety. These types of epidemiological studies often come under the remit of public health agencies, such as the UK Health Security Agency (UKHSA) in England, who are required to undertake surveillance of vaccine preventable diseases, including via seroepidemiological studies and data linkage studies using national level electronic healthcare data. An individual level national vaccine register with an accurate denominator can be the key to gaining insights into vaccine coverage, effectiveness and safety. During the COVID-19 pandemic, England’s first vaccine register was developed. This enabled timely estimates of real-world vaccine effectiveness in the whole population of England, as well as enabling epidemiological investigations of rare potential risks from vaccines in specific populations. Population-based research studies, including prospective cohort studies are complementary to surveillance, and combined, enable more comprehensive assessments. As there was unprecedented investment into research studies and infrastructure during the pandemic, the scale of these studies meant they were able to contribute to vaccine programme evaluations in a way that had not been possible for previous vaccine programmes. In this review, we summarise the different large scale surveillance and research studies that have been used to evaluate and inform vaccine policy from the time of the first data linkage studies undertaken in England in the 1990s to the present day post-COVID-19 pandemic.
State-of-the-Art Review: Complexities in Cardiac Implantable Electronic Device Infections: A Contemporary Practical Approach
Authors: Chesdachai Supavit , Baddour Larry M , Tabaja Hussam , Madhavan Malini , Anavekar Nandan , Zwischenberger Brittany A , Erba Paola Anna , DeSimone Daniel C
Published: February 2025

Cardiac implantable electronic device infections (CIEDIs) present substantial challenges for infectious diseases specialists, encompassing diagnosis, management, and complex decision making involving patients, families, and multidisciplinary teams. This review, guided by a common clinical case presentation encountered in daily practice, navigates through the diagnostic process, management strategies in unique scenarios, long-term follow-up, and critical discussions required for CIEDIs.
Clinical utility and implementation of polygenic risk scores for predicting cardiovascular disease
Authors: Schunkert Heribert , Di Angelantonio Emanuele , Inouye Michael , Patel Riyaz S , Ripatti Samuli , Widen Elisabeth , Sanderson Saskia C , Kaski Juan Pablo , McEvoy John W , Vardas Panos , Wood Angela , Aboyans Victor , Vassiliou Vassilios S , Visseren Frank L J , Lopes Luis R , Elliott Perry , Kavousi Maryam
Published: February 2025

Genome-wide association studies have revealed hundreds of genetic variants associated with cardiovascular diseases (CVD). Polygenic risk scores (PRS) can capture this information in a single metric and hold promise for use in CVD risk prediction. Importantly, PRS information can reflect the causally mediated risk to which the individual is exposed throughout life. Although European Society of Cardiology guidelines do not currently advocate their use in routine clinical practice, PRS are commercially available and increasingly sought by clinicians, health systems, and members of the public to inform personalized health care decision-making. This clinical consensus statement provides an overview of the scientific basis of PRS and evidence to date on their role in CVD risk prediction for the purposes of disease prevention. It provides the reader with a summary of the opportunities and challenges for implementation and identifies current gaps in supporting evidence. The document also lays out a potential roadmap by which the scientific and clinical community can navigate any future transition of PRS into routine clinical care. Finally, clinical scenarios are presented where information from PRS may hold most value and discuss organizational frameworks to enable responsible use of PRS testing while more evidence is being generated by clinical studies.
MEEhubs2024: A hub-based conference on microbial ecology and evolution fostering sustainability
Authors: Wenger Ariane , Bakkeren Erik , Granato Elisa , Tecon Robin , Mitri Sara , Möbius Wolfram
Published: February 2025

Scientific conferences are essential to academic exchange. However, related air travel contributes to greenhouse gas emissions, while expensive registration and travel costs limit the participation of early-career researchers and those from low-income countries. Virtual conferences offer promising solutions for reducing emissions and enhancing accessibility and inclusivity but often limit networking and personal interaction. Hybrid multi-hub conferences, which combine virtually connected in-person venues with individual virtual participation, combine the benefits of both conference formats. Thus, we present and discuss MEEhubs2024, a multi-hub conference on microbial ecology and evolution held in January 2024. During this three-day conference, attendees participated virtually or at one of six hubs in Europe and North America. We analyzed the participants’ and organizers’ feedback to create a template and provide insights into the scientific community's adoption of this new conference format, which was positively evaluated by most participants. Because technical, logistical and structural challenges remain, including limited opportunities to interact and network across hubs and participation modes, we provide recommendations for improvement like hiring technical hosts and offering virtual-only social activities. Finally, we used the participants’ feedback to reflect on conference expectations, highlighting research gaps and the need for organizers to define and communicate goals when organizing conferences.
Institutionalizing linkages between informal healthcare providers and the formal health system in Nigeria: what are the facilitating and constraining contextual influences?
Authors: Onwujekwe Obinna , Mbachu Chinyere Ojiugo , Agyepong Irene , Elsey Helen
Published: February 2025

With most households in rapidly urbanising LMIC cities using private and informal providers for basic healthcare, the need to establish linkages with the formal sector is paramount in the drive for universal health coverage. Successful and effective linkage of informal healthcare providers to the formal health system requires an understanding of prevailing contextual factors and how they can be modulated to support the linkages. Context plays a pivotal role in shaping the nature and success of any integration efforts. This paper, based on a qualitative study explored the facilitating and constraining contextual influences shaping the linkage of informal healthcare providers into the formal health system in governance, service delivery and data reporting. The research was conducted in Enugu and Anambra states in southeastern Nigeria. In-depth interviews were held with 12 senior healthcare managers, 16 primary healthcare facility managers, 32 informal providers and 16 community leaders. Eight sex-disaggregated focus group discussions were held with health service users. Transcripts were coded in NVivo using a pre-defined coding framework comprising facilitators and constraints at the individual, organisational, and environmental levels. Individual factors that influence linkage of informal providers into the formal health system include personal attitudes towards linkage, capacity of informal providers to deliver quality services, nature of existing relationships between formal and informal providers and trust in the formal health system. Organizational factors include leadership structure, coordination and accountability mechanisms, functional management capacity of the formal health system, and multiple regulatory frameworks. External factors include supportive health policies on integration, sustainable funding for continuous training and supportive supervision, and global agenda/support for integration. This study has provided valuable insights for decision makers and practitioners for harnessing the contextual factors to link informal healthcare providers successfully and effectively to the formal health system to improve access to quality health services in urban slums.
Selective enrichment of high-affinity clade II N2O-reducers in a mixed culture
Authors: Laureni Michele , Rubio Francesc Corbera , Kim DaeHyun Daniel , Browne Savanna , Roothans Nina , Weissbrodt David G , Olavaria Karel , de Jonge Nadieh , Yoon Sukhwan , Pabst Martin , van Loosdrecht Mark C M
Published: February 2025

Microorganisms encoding for the N2O reductase (NosZ) are the only known biological sink of the potent greenhouse gas N2O, and are central to global N2O mitigation efforts. Clade II NosZ populations are of particular biotechnological interest as they usually feature high N2O affinities and often lack other denitrification genes. We focus on the yet-unresolved ecological constraints selecting for different N2O-reducers strains, and controlling the assembly of N2O-respiring communities. Two planktonic N2O-respiring mixed cultures were enriched at low dilution rates under limiting and excess dissolved N2O availability to assess the impact of substrate affinity and N2O cytotoxicity, respectively. Genome-resolved metaproteomics was used to infer the metabolism of the enriched populations. Under N2O limitation, clade II N2O-reducers fully outcompeted clade I affiliates, a scenario previously only theorized based on pure-cultures. All enriched N2O-reducers encoded and expressed the sole clade II NosZ, while also possessing other denitrification genes. Two Azonexus and Thauera genera affiliates dominated the culture, and we hypothesize their coexistence to be explained by the genome-inferred metabolic exchange of cobalamin intermediates. Under excess N2O, clade I and II populations coexisted, yet proteomic evidence suggests that clade II affiliates respired most of the N2O, de facto outcompeting clade I affiliates. The single dominant N2O-reducer (genus Azonexus) notably expressed most cobalamin biosynthesis marker genes, likely to contrast the continuous cobalamin inactivation by dissolved cytotoxic N2O concentrations (400 μM). Ultimately, our results strongly suggest the solids dilution rate to play a pivotal role in controlling the selection among NosZ clades, albeit the conditions selecting for genomes possessing the sole nosZ remain elusive. We furthermore highlight the potential significance of N2O-cobalamin interactions in shaping the composition of N2O-respiring microbiomes.
What is it like living with X-linked hypophosphataemia?: results from an Australian consumer survey
Authors: Sandy Jessica L , Ford Naomi , Bevc Sandy , Rodda Christine , Siafarikas Aris , Simm Peter , Collins Lucy , Wall Christie-Lee , Biggin Andrew , Munns Craig F
Published: February 2025

X-linked hypophosphataemia (XLH) is a rare, X-linked dominant condition with a high burden of both physical and psychosocial disease. This study aimed to describe the experience and burden of disease for children and adults living with XLH in Australia by inviting affected individuals and their carers to complete an online questionnaire.

Of the 46 responses, half were completed by a person with XLH, and half by carers. Thirty percent were male, 33% were aged less than 18 years. Median age at diagnosis was two years (IQR 1.5-3.0).

There was a high burden of surgical intervention: 59% reported five or more surgeries and 33% (15) had major dental procedures. Bone deformities and painful bones/joints were rated as the most impactful symptoms for both children and adults with XLH with 54% of participants rating emotional and physical burden of disease as equally impactful.

Participants reported experiencing many psychosocial and financial challenges, including mental health disorders (including depression, anxiety, suicidal ideation, and self-harm), discrimination, and social isolation.

Seventy percent reported it was difficult or very difficult living with XLH. Over 80% percent strongly agreed that lack of XLH awareness impacts on support services and health funding and agreed or strongly agreed that it is hard living with a condition that most Australians have never heard of.

XLH imparts a high physical, emotional, psychosocial, and mental toll on affected individuals. While the most impactful reported symptoms were musculoskeletal features, this survey emphasises the degree of social and psychological challenges that individuals with XLH face. Some of these difficulties appear to be worsened by a lack of awareness. Patient advocacy and improving knowledge of rare diseases such as XLH is a key role of health professionals and should improve overall experience for affected individuals.
Ethos of Power in Competition Law Enforcement in Labour Markets
Authors: Karlsson Haukur Logi
Published: February 2025

Monopsony power over the purchase of labour, which is used as a factor in the production of consumer products, will usually not be detected as a harmful concentration within a competition law enforcement paradigm that emphasizes consumer welfare. This problem is integral to the economics-based welfare approach to competition law enforcement. By focusing on specific economic results as a benchmark for enforcement priorities, using partial equilibrium analysis as an analytical method, the enforcement effort risks being blindsided by variables that are not being analysed. Expanding the partial equilibrium analysis to include additional variables, or by attempting a general equilibrium analysis, makes the practical task of competition law enforcement impossibly complicated. In this paper, an alternative approach to rationalize competition law enforcement in the context of labour markets is theorized. Instead of using the currently orthodox welfare-centred approach, an argument for viewing competition law in deontological terms as a means for defusing power is advanced. It is argued that by viewing competition enforcement as a tool for regulating power in the marketplace, a special complementary role could be defined for competition enforcement in labour markets. This approach is inspired by the German ordoliberal project and Galbraith’s concept of countervailing power.
Single frontotemporal approach for microsurgical clipping of bilateral ophthalmic artery aneurysms: a case report
Authors: Sanchez-Orbegoso Orlando , Bocanegra-Becerra Jhon E , Rabanal-Palacios Jorge , Yaya-Loo Hector
Published: February 2025

Bilateral ophthalmic aneurysms represent a distinct niche of brain aneurysms located in a complex skull base region. When considering surgical treatment, a single-stage approach is often advantageous to minimize operative time, tissue manipulation, and damage to neural and vascular structures compared to a two-stage surgery. Nonetheless, this procedure is not exempt from risks, given that thorough knowledge, preoperative and intraoperative judgment can be necessary to reduce the significant risk of bilateral vision loss. Thus, a tailored approach often is needed. In this study, we present the case of a 53-year-old female who was diagnosed with bilateral ophthalmic aneurysms during the work-up for chronic headaches. Because of the growth pattern and imminent risk of rupture, she underwent elective microsurgical treatment. A frontotemporal approach ipsilateral to the most lobulated aneurysm was performed. Both aneurysms were successfully clipped in a single craniotomy. Her postoperative imaging demonstrated adequate clipping and an uneventful clinical course. Our case outlines the feasibility of a single approach and contributes to the tailored selection for patients when considering microsurgical treatment for these complex lesions.
Breach of Contract: An Overview
Authors: Zeller Bruno
Published: February 2025

This chapter examines transnational generic contract law principles of remedial relief. Not all contracts run their intended course, and a breach will most likely result in damages to at least one party. The intention of the law is to secure the bargain, but this security is only as good as the ability of courts and tribunals to award appropriate remedies in cases of breach of contract. The ability to award damages is an important economic function, and it is not surprising to find laws regulating the awarding of damages in a variety of legal documents. Indeed, the United Nations Convention on Contracts for the International Sale of Goods (CISG) has recognized that the awarding of damages is an important, if not the most important, remedy and structured its remedial system in such a way that damages can always be claimed irrespective of any other claims.
Breach of Contract: The CISG
Authors: Zeller Bruno
Published: February 2025

This chapter details the remedial provisions of the United Nations Convention on Contracts for the International Sale of Goods (CISG). The CISG has two articles, namely Articles 45 and 61, which provide an overview of the remedies available to the buyer or the seller in the event of a breach. Article 45(2) for the buyer and Article 61(2) for the seller make it clear that damages provide the most important and all-embracing remedy, as both the buyer and seller never lose the right to damages even if they choose another remedy. In addition, parties to a sale are relieved of liability for a breach of contract only by Article 79, which indicates that only an impediment beyond the control of the party will excuse non-performance. The CISG allows for three broad categories of remedies: specific performance, avoidance, and substitutionary relief.
Limitation on Claims within Article 74
Authors: Zeller Bruno
Published: February 2025

This chapter looks at the limitations on the right to claim damages under the United Nations Convention on Contracts for the International Sale of Goods (CISG). A breach of a contract within the CISG does not give unlimited access to damages. Thus, it must be stressed that principles limiting damages must be found within the four corners of the CISG and there should be no recourse to domestic principles. Three limiting factors need to be considered: the foreseeability rule contained in Article 74; a duty to mitigate damages by the promisee pursuant to Article 77; and the exemption from paying damages for those breaches that are due to an impediment beyond the control of the breaching party pursuant to Article 79.
Calculation of Losses under Article 74
Authors: Zeller Bruno
Published: February 2025

This chapter explains how losses pursuant to Article 74 of the United Nations Convention on Contracts for the International Sale of Goods (CISG) are to be calculated. Article 74 clearly stipulates that the plaintiff can claim only losses that have been suffered as a consequence of the breach. Losses are divided or categorized into direct losses, incidental losses, consequential losses, and loss of profit. Article 74 does not specifically mention a concrete calculation and therefore does not directly disallow an abstract one either. However, the tone of the article certainly suggests that losses, in order to be proven, should be calculated on a concrete basis. Arguably, a hypothetical or abstract calculation can be accepted if both parties agree to it, but any unilateral suggestion of an abstract nature appears to be rejected by the courts.
Special Damages: Interest Rates
Authors: Zeller Bruno
Published: February 2025

This chapter assesses the right to claim interest under Article 78 of the United Nations Convention on Contracts for the International Sale of Goods (CISG). The advantage of relying on Article 78 is obviously the fact that losses do not need to be proven and that the limitation of Article 79 also does not apply. The problem is that Article 78 may not provide full compensation, but a claim pursuant to Article 78 may still be the fastest and cheapest way to get an award. In summary, Article 78 is to be understood in two ways. First, the interest rate issue is not governed by the convention, and therefore the conflict of laws rules will determine the applicable domestic law. Second, it appears that the majority of courts follow this suggestion; in other words, jurisprudence supports the view that the rate of interest has to be set via domestic law.
Attorneys’ Fees
Authors: Zeller Bruno
Published: February 2025

This chapter shows that attorneys’ fees arguably can be defined as substantive and also a procedural matter, and hence are either included under Article 74 or not. Article 74, in the spirit of the United Nations Convention on Contracts for the International Sale of Goods (CISG), contains no direct reference to individual classes of losses except loss of profit. The answer to whether attorneys’ fees were intended to be included in the sphere of the provision lies in the application of the general principles on which the CISG relies. Great care must be taken to distinguish between court costs and legal fees if any autonomous interpretation of Article 74 is to be developed. Even so, tribunals and courts throughout the CISG realm do not agree on this matter. This is demonstrated by comparing cases from different jurisdictions.
Penalty Clauses and the CISG
Authors: Zeller Bruno
Published: February 2025

This chapter explores whether the issue of penalty clauses is within the mandate of the United Nations Convention on Contracts for the International Sale of Goods (CISG) or falls under the exception of Article 4. Whether penalty clauses are governed by the CISG is still a controversial issue and hence unresolved. The issue is that in civil law, the court has discretion to either enforce a penalty clause or moderate it, when in common law, a penalty clause is unenforceable. The added difficulty of the CISG is the fact that it was constructed as a compromise between the civil and common law systems. As a result, differences between the two systems will, in some cases, present different solutions. As far as the CISG is concerned the main argument either for or against an inclusion of penalty clauses revolves around the interpretation of Articles 4 and 74.
Exemptions
Authors: Zeller Bruno
Published: February 2025

This chapter studies the effects of unforeseen circumstances on a contract. The approach to changed circumstances varies from country to country, and there is simply no uniformity in approach. The classic concepts of force majeure and hardship are the basis on which attempts have been made to solve the problem of non-performance of a contract. Generally speaking, the aim of force majeure is to settle a contract through either suspension or termination of obligations. However, termination of a contract is always the last resort. The United Nations Convention on Contracts for the International Sale of Goods (CISG) attempts to keep the contract alive as long as is practicably possible. Article 79 indicates that a settlement of the dispute and hence a continuation of contractual obligations is possible. Only in cases where the impediment falls under Articles 49 and 25 can the contract be avoided.
The Doctrine of Anticipatory Repudiation
Authors: Zeller Bruno
Published: February 2025

This chapter addresses how the United Nations Convention on Contracts for the International Sale of Goods (CISG) governs anticipatory repudiation of a contract. Under the CISG, anticipatory breach does not pose any problems but is different from the common law position. The differences are in the application and in the terminology. A party under the CISG can resolve a potential unease whether the other party will perform in a two-step approach unlike under common law where repudiation is the only approach. Importantly, the CISG governs two situations. First, a party can suspend its own performance once it suspects that the other party will not perform. Secondly, the innocent party can avoid the contract without having to wait until the contract is actually breached, thereby allowing the applicability of the principles of fundamental breach.
Conclusion and Observations
Authors: Zeller Bruno
Published: February 2025

This concluding chapter argues that two important factors need to be taken into account at a time when the pace of globalization and internationalization of trade has quickened. First, an understanding of the problems of devising and implementing uniform and harmonized laws is necessary. Second, existing international conventions, such as the United Nations Convention on Contracts for the International Sale of Goods (CISG), that offer practical solutions to harmonization must be recognized and adopted by the legal profession when drafting international contracts. Ultimately, unification of laws will depend on internationalization and respect for other systems’ decisions. As such, the uniform European laws must be replaced by uniform international laws as trade spans international borders.
Evaluating predictors of ocular complications and mortality in candidemia: Are repeat blood cultures key?
Authors: Iqbal Hamail , Nikolic Dejan , Foppiano Palacios Carlo
Published: February 2025

Candidemia can lead to ocular complications, including endophthalmitis and chorioretinitis. Management of candidemia traditionally included ophthalmic exams. However, due to concerns regarding the utility of performing ophthalmic exams in all patients, there is a need for prognostic factors suggestive of ocular complications. We sought to evaluate if positive follow-up blood cultures (FUBC) are associated with ocular involvement in candidemia.

We conducted a single-center, retrospective review of candidemia cases at an academic medical center (2017–2022). Data on demographics, risk factors, ophthalmic exams, eye infection, and mortality outcomes were collected. Data was analyzed using descriptive statistics, χ2 tests, and multivariate logistic regression.

A total of 238 episodes of candidemia among 199 patients were included. FUBC were obtained for 97% of cases and were positive in 35%. Ophthalmic exams were performed in 82% of cases and identified 10 endophthalmitis and 11 chorioretinitis cases. There was no significant association between positive FUBC and endophthalmitis or chorioretinitis. Ocular infections were associated with presence of any visual symptom (P < .001), Candida albicans (P = .02), C. dubliniensis (P = .003), and length of antifungal regimen (P = .007). Hospital mortality was associated with age (P < .001), C. lusitaniae (P = .056), acquisition of FUBC (P = .03), completion of an ophthalmic exam (P = .046), vasopressor use (P < .001), and length of antifungal regimen (P = .009).

While positive FUBC did not correlate with ocular candidiasis, specific Candida species were associated with endophthalmitis and chorioretinitis. C. lusitaniae infections, acquisition of FUBC, and ophthalmic exam were predictors of hospital mortality. Other indications for ophthalmic evaluations and further identification of mortality risk factors need to be investigated.
Establishing an accurate infrared band strength for the cyanate ion in interstellar ices
Authors: Gerakines Perry A , Materese Christopher K , Hudson Reggie L
Published: February 2025

A prominent infrared (IR) spectral feature near 2165 cm−1 (λ = 4.62 $\mu$m) in interstellar ices has been attributed to the cyanate ion (OCN−) for almost 40 yr, but firm, first-principles solid-phase IR data for quantifying IR-astronomical observations of OCN− in a H2O-rich amorphous ice have never been published. Here we report the first laboratory study that delivers such an IR band strength for OCN− that is reproducible and free of ambiguous uncertainties concerning ice density, thickness, and temperature, providing new quantitative results for both observational and laboratory astronomers. Additional results include the first robust measurements of IR band strengths of isocyanic acid (HNCO), ammonia (NH3), and the ammonium ion (NH4+) in H2O-rich ice.
Context-specific inhibition of mitochondrial ribosomes by phenicol and oxazolidinone antibiotics
Authors: Bibel Brianna , Raskar Tushar , Couvillion Mary , Lee Muhoon , Kleinman Jordan I , Takeuchi-Tomita Nono , Churchman L Stirling , Fraser James S , Fujimori Danica Galonić
Published: February 2025

The antibiotics chloramphenicol (CHL) and oxazolidinones, including linezolid (LZD), are known to inhibit mitochondrial translation. This can result in serious, potentially deadly, side effects when used therapeutically. Although the mechanism by which CHL and LZD inhibit bacterial ribosomes has been elucidated in detail, their mechanism of action against mitochondrial ribosomes has yet to be explored. CHL and oxazolidinones bind to the ribosomal peptidyl transfer center (PTC) of the bacterial ribosome and prevent incorporation of incoming amino acids under specific sequence contexts, causing ribosomes to stall only at certain sequences. Through mitoribosome profiling, we show that inhibition of mitochondrial ribosomes is similarly context-specific—CHL and LZD lead to mitoribosome stalling primarily when there is an alanine, serine, or threonine in the penultimate position of the nascent peptide chain. We further validate context-specific stalling through in vitro translation assays. A high-resolution cryo-electron microscopy structure of LZD bound to the PTC of the human mitoribosome shows extensive similarity to the mode of bacterial inhibition and also suggests potential avenues for altering selectivity. Our findings could help inform the rational development of future, less mitotoxic, antibiotics, which are critically needed in the current era of increasing antimicrobial resistance.
Site-specific free energy surface parameters from single-molecule fluorescence measurements of exciton-coupled (iCy3)2 dimer probes positioned at DNA replication fork junctions
Authors: Maurer Jack , Albrecht Claire S , von Hippel Peter H , Marcus Andrew H
Published: February 2025

Single-stranded–double-stranded DNA (ss–dsDNA) replication forks and primer-template junctions are important recognition sites for the assembly and function of proteins involved in DNA replication, recombination, and repair. DNA ‘breathing’ – i.e. thermally induced local fluctuations of the sugar-phosphate backbones and bases – can populate metastable conformational macrostates at positions near such junctions and likely play key roles in the functional interactions of the regulatory proteins that bind at these sites. Recently, Maurer et al. [1] performed polarization-sweep single-molecule fluorescence (PS-SMF) studies on exciton-coupled (iCy3)2 dimer-labeled ss–dsDNA fork constructs, which revealed that the nucleobases and backbones immediately adjacent to the dimer probes undergo conformational fluctuations on time scales ranging from hundreds of microseconds to hundreds of milliseconds. The local conformations sensed by the dimer probes consist of four quasi-stable macrostates whose populations and dynamics depend on dimer probe position relative to these junctions. Here we present theoretical analyses of these PS-SMF data that quantify the relative stabilities and activation barriers of the free energy surfaces of site-specific DNA ‘breathing’ events at key positions within these junctions. Our results suggest a detailed molecular picture for DNA ‘breathing’ at these positions, thus providing insights into understanding the molecular mechanisms of the proteins that operate at these sites.
How Do Chinese Smokers Respond to Cigarette Price? Evidence From a Nationwide Household Survey
Authors: He Aduqinfu , Wang Zeyu , Zheng Rong
Published: February 2025

Introduction

Despite the Chinese government’s implementation of tax increases in 2009 and 2015 to curb tobacco use, the anticipated decline in cigarette sales has not materialized. This suggests a need for a deeper understanding of smokers’ demand behavior. The present study aims to provide a more accurate estimation of the price and income elasticities of cigarettes in China.

Methods

We utilized Deaton’s model to analyze a comprehensive micro-level dataset comprising 10 892 households surveyed in the 2012 wave of the China Family Panel Survey, with the aim of estimating the price and income elasticities of cigarette demand, as well as to investigate how these elasticities vary across different income brackets. These resulting elasticities were subsequently integrated into the World Health Organization Tax Simulation Model to simulate the potential impacts of various tax increase scenarios on cigarette consumption and tax revenue.

Results

The price elasticity in China hovers around −0.72, with an income elasticity of about 0.23. Heterogeneity analysis indicated that lower-income smokers exhibit greater sensitivity to price changes. Policy simulations suggested that tax increases would substantially reduce consumption while concurrently increasing tax revenue.

Conclusions

Chinese smokers exhibited a considerable sensitivity to cigarette prices, underscoring the efficacy of taxation as a policy instrument for shaping smoking behavior. As tax reforms continue and cigarette retail prices increase, there lies promising potential for achieving tobacco control goals, generating additional revenue, and improving social equality.

Implications

A primary contribution of this study is the provision of a more reliable estimation of cigarette price and income elasticities in China. These parameters are crucial for assessing the potential impact of tobacco tax increases on cigarette consumption and government revenue. By leveraging a nationally representative survey from 2012 and employing Deaton’s identification strategy, we significantly enhanced the data quality and methodological rigor of our analysis, leading to more accurate estimation results compared to previous studies.
Mycobacterium bovis Infections Following Intravesical Bacillus Calmette-Guérin Instillation for Bladder Cancer in Western Australia: A 22-Year Retrospective Review
Authors: Manickavasagar Usha , Nel Henco , Seet Jason , Varrone Liana , Keehner Terillee , McCann Rebecca , Barnes Rosie , Jacques Angela , Clohessy Penelope
Published: February 2025

Mycobacterium bovis bacillus Calmette-Guérin (BCG) infection following intravesical BCG instillation is a rare complication of therapy that is associated with significant morbidity and mortality. We conducted a multicenter retrospective review of microbiologically confirmed M.bovis BCG infections in Western Australia over 22 years. Thirty-three patients were included in our study. All patients were male with a median age of 72 years. Localized infections accounted for 22/33 cases while disseminated infections accounted for 11/33 cases. The majority (n = 21) of positive isolates were cultured from urine specimens, followed by tissue and blood. The median time between first BCG instillation and infection was 7.5 months (95% CI, 3.5–11.5). The median duration of antimycobacterial therapy for localized infections was 6 months (95% CI, 4.1–7.9) as compared with 9 months (95% CI, 7.9–10.1) for disseminated infections (P = .039). The attributed mortality was 14.3%. M.bovis BCG infections have diverse clinical presentations and clinicians must have a high index of suspicion when assessing patients with a history of intravesical BCG instillation.
Clinical Comparison of the COVID Waves 2-5. An Inpatient Retrospective Comparative Analysis from Karachi, Pakistan
Authors: Sayeed Muneeba Ahsan , Shalim Elisha , Farman Shaiza , Farooqui Fizza , Syed Beenish , Ahmed Ishfaque , Iqbal Anika , Kumar Aneel , Akhter Raniyah , Hyder Furkan , Shah Hasan Ali , Hussain Adeel , Rasheed Sarwat , Afshan Saba , Salik Nukrich Rizwana , Raza Madiha , Rehman Haseeb U , Razzaque Abdul , Rajput Abdul Wahid , Quraishy Muhammad Saeed
Published: February 2025

Background

Each COVID wave is unique in its clinical presentation and outcome. In this study, we compared the clinical characteristics and outcome of COVID waves 2-5 in inpatient settings.

Methods

A retrospective study was conducted at the Sindh Infectious Diseases Hospital and Research Center on adult patients who were admitted with a positive COVID PCR from July 2020–Mar 2022. SPSS 26 analyzed data.

Results

Total 3190 COVID-19 patients were admitted. Wave 2 had the highest percentage of discharges compared to mortality (81%, p-value 0.0001). Cytokine Release Syndrome (CRS) was most common in wave 3 (32.7%, p-value 0.0001). On comparison, severe COVID on admission was predominant in wave 4 (79.4%, p-value 0.0001) with highest intubation rate (27.1%, p-value 0.0001), septic shock (24.3%, p-value 0.0001) and disease progression (50.8%, p-value 0.0001). In wave 5 majority were elderly (median age 68 years), had mild COVID (22.4%, p-value 0.0001), most having co-morbidities (84.6%, p-value 0.0001) and ratio of acute kidney injury was high (29.2%, p-value 0.0001). Mortality was lowest in wave 2 (18.9%, p-value 0.0001) while highest in wave 4 (42.5%, p-value 0.0001; OR 3.18, CI 2.6-3.8 compared to wave 2).

Conclusion

Each wave had some unique characteristics compared to other waves with wave 4 being the deadliest one in terms of disease severity and outcome, which was driven by delta variant.
Predictive linear seesaw model with Δ(27) family symmetry.
Authors: Hernández A E Cárcamo , de Medeiros Varzielas Ivo , González Juan Marchant
Published: February 2025

We propose a model where the active neutrino masses are produced through the linear seesaw mechanism. The model uses a Δ(27) family symmetry to address the flavour problem. The model is predictive in the leptonic sector and predict rates for Lepton Flavour Violation processes within the experimental sensitivity reach.
Sex differences in the impact of multimorbidity on long-term mortality for patients with colorectal cancer: a population registry-based cohort study
Authors: Ng Shu Kay , Baade Peter , Wittert Gary , Lam Alfred K , Zhang Ping , Henderson Saras , Goodwin Belinda , Aitken Joanne F
Published: February 2025

Background

Women have better survival than men patients with colorectal cancer (CRC), but the extent to which this is due to multimorbidity is unclear.

Methods

A population-based study of 1843 patients diagnosed with CRC in Australia. Data included patient’s demographics, multimorbidity, tumour histology, cancer stage, and treatment. We estimated the risks of all-cause mortality and cause-specific mortality due to cancer or non-cancer causes.

Results

Men had lower survival than women (P ≤ 0.010) amongst those diagnosed at Stages I-III (15-year survival: 56.0% vs 68.0%, 48.5% vs 60.7%, 34.8% vs 47.5%, respectively), excepting Stage IV (14.4% vs 12.6%; P = 0.18). Married men exhibit better survival than those who were never married (P = 0.006). Heart attacks (9.9% vs 4.3%, P < 0.001) and emphysema (4.8% vs 2.1%, P = 0.004) were more prevalent in men than women. Comorbid stroke and high cholesterol (adjusted hazard ratio, AHR = 2.22, 95% confidence interval, CI = 1.17–4.21, P = 0.014) and leukaemia (AHR = 6.36, 95% CI = 3.08–13.1, P < 0.001) increased the risk of cancer death for men only. For women, diabetes increased the risk of all-cause death (AHR = 1.38, 95% CI = 1.02–1.86, P = 0.039) and high blood pressure increased the risk of death due to non-cancer causes (AHR = 2.00, 95% CI = 1.36–2.94, P < 0.001).

Conclusion

Separate models of CRC care are needed for men and women with consideration of multimorbidity and social factors.
Predictors of response to intravenous immunoglobulin in patients with dermatomyositis: the ProDERM study
Authors: Charles-Schoeman Christina , Schessl Joachim , Bata-Csörgő Zsuzsanna , Dimachkie Mazen M , Griger Zoltan , Moiseev Sergey , Oddis Chester V , Schiopu Elena , Vencovský Jiri , Clodi Elisabeth , Levine Todd , Aggarwal Rohit
Published: February 2025

Objectives

The phase 3 ProDERM study demonstrated intravenous immunoglobulin (IVIg) was safe and effective in patients with dermatomyositis (DM). This analysis assessed clinical and serological predictors of IVIg response in DM patients from ProDERM.

Methods

ProDERM was a prospective, randomised, placebo-controlled study of DM patients. For Weeks 0–16, patients received 2.0 g/kg IVIg (Octagam, 10%) or placebo every 4 weeks. Eligible patients entered the open-label extension phase, where all received IVIg to week 40. Univariate and multivariate analyses examined associations between baseline variables and total improvement score (TIS), including myositis disease activity assessment tool (MDAAT; assessing different organ involvement), and myositis-specific and myositis-associated autoantibodies.

Results

Ninety-five patients were enrolled. Univariate analyses found no significant association between TIS at week 16 or 40 and age; sex; ethnicity; disease duration/activity; cutaneous, skeletal, gastrointestinal or muscle disease activity; or previous failed or concomitant medications.

Multivariate analysis found patients with higher MDAAT cutaneous scores had a better chance of at least minimal TIS improvement. Higher MDAAT pulmonary scores were associated with a lower, but still considerable, chance of improvement. Patients with TIF1-γ antibodies had a better TIS response; however, after controlling for cutaneous disease activity, there was no significant association between antibody classification (including anti-TIF1-γ) and efficacy outcome.

Conclusion

IVIg was effective in treating DM patients regardless of demographic features and autoantibody status (for most autoantibodies). Patients with higher cutaneous disease activity and/or anti-TIF1-γ responded best to IVIg, while pulmonary disease activity predicted a lower, but still effective, IVIg response, warranting further investigation.

Clinical trial registration

ClinicalTrials.gov, NCT02728752.
Efficacy of biorational and synthetic fungicides for control of brown rot blossom blight in peach, 2024
Authors: Wesche Johanna , Schnabel Guido , Hopkins Jeffrey
Published: February 2025

Brown rot blossom blight, caused by the fungal pathogen Monilinia fructicola, is a significant disease of peach in humid peach production regions of the southeastern United States. Blighted blossoms and infected twigs provide secondary inoculum for subsequent fruit infections. Necrotic flowers turn brown and stick firmly to the twig in a gummy mass. This report evaluates the efficacy of spray programs with conventional and biorational fungicides for the management of brown rot blossom blight. The trial was conducted in 2024 in Seneca, SC on 10-year-old Prunus persica var. nucipersica ‘Juneprincess’ peaches. Results from these trials will help advise U.S. peach producers in developing management programs for this disease.
Medication for Opioid Use Disorder for Hospitalized Patients at Six New York City Public Hospitals with an Addiction Consult Service
Authors: Rostam-Abadi Yasna , McNeely Jennifer , Tarpey Thaddeus , Fernando Jasmine , Appleton Noa , Fawole Adetayo , Mazumdar Medha , Kalyanaraman Marcello Roopa , Cooke Caroline , Dolle Johanna , Siddiqui Samira , Schatz Daniel , King Carla
Published: February 2025

Objectives

We explored medications for opioid use disorder treatment (MOUD) utilization in six New York City public hospitals that implemented the “Consultation for Addiction Care and Treatment in Hospitals (CATCH)” program.

Methods

CATCH rolled out between October 2018 and February 2020. Data from the electronic health record were analyzed for the first year post-implementation. Eligible cases included adults with an opioid-related diagnosis admitted to inpatient departments served by CATCH, with a stay of ≥1 night. Patients were classified as receiving an MOUD order if there was at least 1 order of buprenorphine, methadone, or naltrexone. Logistic regression modeled the impact of CATCH consults on MOUD orders, controlling for demographic and clinical characteristics with hospital as a random effect.

Result

Among 2117 eligible patients, 71.4% were male, with a mean age of 51.2 years, and 27.2% identified as Black, 21.2% as White, and 34.5% as Hispanic. MOUD was ordered in 60.9% of admissions, and 41.5% had a completed CATCH consult. Patients identified as Black had lower odds of receiving a MOUD order than those identified as White (OR: 0.52, 95% CI: 0.38–0.71; P < 0.001). Patients with a CATCH consult had higher odds of receiving a MOUD order (OR: 3.22, 95% CI: 2.54–4.07; P < 0.001).

Conclusion

Majority of patients in our sample received a MOUD order, with higher odds among those with a CATCH consult. Further research is needed on the drivers of racial disparities in MOUD, and other contextual, organizational, and population-specific barriers and facilitators contributing to receipt of hospital-based addiction consult services and MOUD.
Language Complexities for Deaf and Hard of Hearing Individuals in Their Pursuit of a Career in Science, Technology, Engineering, Mathematics, and Medicine: Perspectives From an LSL/ASL User
Authors: Adler Henry J.
Published: February 2025

A research scientist with 35 years of experience in the field of hearing research, the author writes that his own experiences have provided a perspective that may be valuable for both future d/Deaf and Hard of Hearing (D/HH) individuals and their peers with typical hearing in their pursuit of a career in Science, Technology, Engineering, Mathematics, and Medicine (STEMM). The author first describes the role of Hearing Inclusive-Association for Research in Otolaryngology in enhancing inclusivity and accessibility for D/HH scientists in the field of Hearing Research. Second, the challenges faced by D/HH scientists arise from the difficulties of working with peers with typical hearing, resulting in less inclusivity and accessibility for the D/HH scientists. The next section deals with solutions to these challenges, including American Sign Language interpreters, websites that give advice on inclusivity and accessibility, and technological advances such as assistive listening devices and smartphones with a capacity for auto captioning. The solutions, however, are fraught with issues such as limited budgets and misperception. Fourth, the author argues that the experiences necessary for a career in STEMM may require a higher-than-expected degree of collaboration with peers with typical hearing outside the laboratory. Finally, studies on successful D/HH scientists in STEMM fields should include experiences of obtaining successful research funding.
Applying the Purpose, Autonomy, Confidence, Engrossment Model of Motivational Design to Support Motivation for Continuing Professional Development
Authors: Gavarkovs Adam G. , Glista Danielle , O'Hagan Robin , Moodie Sheila
Published: February 2025

Health professionals' motivation is a key determinant of their continuing professional development (CPD) outcomes. Therefore, CPD providers must ensure that they design CPD activities to support health professionals' motivation; this process is referred to as motivational design. The aim of this article is to introduce CPD providers to the PACE (purpose, autonomy, confidence, engrossment) model of motivational design, and describe how we applied the PACE model to create two online modules for an interprofessional audience. The PACE model builds on other available models of motivation design by offering theoretically informed strategies to support autonomous motivation, a specific quality of motivation that is associated with more effective learning processes and outcomes. Our experience suggests that CPD providers can use the PACE model to guide their motivational design efforts. We also encourage CPD researchers to test the theoretical assumptions that inform the PACE model.