bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of MHC IIB Diversity Across Cichlid Fish Radiations
Authors: Lozano-Martín Carlos , Bracamonte Seraina E , Barluenga Marta
Published: June 2023

The genes of the major histocompatibility complex (MHC) are among the most polymorphic genes in vertebrates and crucial for their adaptive immune response. These genes frequently show inconsistencies between allelic genealogies and species phylogenies. This phenomenon is thought to be the result of parasite-mediated balancing selection maintaining ancient alleles through speciation events (trans-species polymorphism [TSP]). However, allele similarities may also arise from postspeciation mechanisms, such as convergence or introgression. Here, we investigated the evolution of MHC class IIB diversity in the cichlid fish radiations across Africa and the Neotropics by a comprehensive review of available MHC IIB DNA sequence information. We explored what mechanism explains the MHC allele similarities found among cichlid radiations. Our results showed extensive allele similarity among cichlid fish across continents, likely due to TSP. Functionality at MHC was also shared among species of the different continents. The maintenance of MHC alleles for long evolutionary times and their shared functionality may imply that certain MHC variants are essential in immune adaptation, even in species that diverged millions of years ago and occupy different environments.
Theme and sentiment of posts in a weight loss subreddit predict popularity, engagement, and users’ weight loss: a computational approach
Authors: Yang Qinghua , Ledbetter Andrew M , Zhuang Jie , Richards Adam S
Published: June 2023

Despite the common use of social media to discuss health issues, little is known about how features of user-generated content influence users’ health outcomes. To address this gap, we longitudinally studied large-scale conversations on the subreddit r/loseit, an online weight loss community, by computationally analyzing the themes and sentiment of users’ posts and examining their associations with users’ self-reported weight loss. Our study identified 28 distinct topics on r/loseit, many of which significantly predicted post score and the number of responsive comments. We also found that the post score was predicted by positive sentiments, whereas the number of comments was predicted by negative sentiments. Further, users’ posts on the topic of goal setting significantly predicted their self-reported weight loss, and such association was amplified when the post score and the number of comments are high. Our findings have important theoretical and practical implications for the relationship between interactions in online communities and health outcomes.
GWAS identifies candidate genes controlling adventitious rooting in Populus trichocarpa
Authors: Nagle Michael F , Yuan Jialin , Kaur Damanpreet , Ma Cathleen , Peremyslova Ekaterina , Jiang Yuan , Zahl Bahiya , Niño de Rivera Alexa , Muchero Wellington , Fuxin Li , Strauss Steven H
Published: June 2023

Adventitious rooting (AR) is critical to the propagation, breeding, and genetic engineering of trees. The capacity for plants to undergo this process is highly heritable and of a polygenic nature; however, the basis of its genetic variation is largely uncharacterized. To identify genetic regulators of AR, we performed a genome-wide association study (GWAS) using 1148 genotypes of Populus trichocarpa. GWASs are often limited by the abilities of researchers to collect precise phenotype data on a high-throughput scale; to help overcome this limitation, we developed a computer vision system to measure an array of traits related to adventitious root development in poplar, including temporal measures of lateral and basal root length and area. GWAS was performed using multiple methods and significance thresholds to handle non-normal phenotype statistics and to gain statistical power. These analyses yielded a total of 277 unique associations, suggesting that genes that control rooting include regulators of hormone signaling, cell division and structure, reactive oxygen species signaling, and other processes with known roles in root development. Numerous genes with uncharacterized functions and/or cryptic roles were also identified. These candidates provide targets for functional analysis, including physiological and epistatic analyses, to better characterize the complex polygenic regulation of AR.
Contested Disability: Sickle Cell Disease
Authors: Srikanthan Sinthu
Published: June 2023

The world’s first “molecular disease,” sickle cell disease (SCD) has captivated the medical community’s attention as a multisystem blood disorder linked to abnormalities in one molecule: hemoglobin. While the molecular model of SCD has led to advances in medical management, its reductionism obfuscates the sociopolitical dimensions of the condition, affording little attention to the racialized, gendered, classed, and disabling disparities faced by people with SCD. Consequently, SCD is frequently contested as a disability—opportunities to support people with SCD in everyday challenges escape many healthcare providers. These trends speak to the legacy of anti-Black racism in the Global North, which deeply entwines disability with racialized boundaries of citizenship and broader debates about “deservingness” of welfare. To address these gaps, this article delineates the medical and social models of disability as well as anti-Black racism to explore how social workers can embed human rights for people with SCD in everyday practice. This article is contextualized in Ontario, Canada, a province that recently launched a quality standard, Sickle Cell Disease: Care for People of All Ages.
State-centric proportionality analysis in Chinese administrative litigation
Authors: Xiao Shiling
Published: June 2023

This article examines the application of proportionality in Chinese administrative litigation over the last two decades and argues that courts in administrative litigation that serve the party-state and tend to uphold state/collective interest have altered proportionality to be state-centric. It finds that the courts invoked proportionality in a negligible portion of all administrative litigation judgments and had inadequate emphases on protecting individual rights. Proportionality has not appreciably assisted the courts in enhancing their oversight of governmental power and protection of individual rights. This article suggests that this is attributable to the restricted function of administrative litigation in China’s party-state governance structure and owing to the country’s long-held belief that public interest takes precedence over individual rights. Administrative litigation, which China’s ruling party employs to resolve principal–agent issues, is seriously constrained. The courts are expected to review the formal legality of executive actions, but not their substance. Informed by the Chinese human rights belief, which favors collectivism over individualism, the courts are skewed toward public interest in the balancing analysis when applying proportionality.
From Norm Violations to Norm Development: Deviance, International Institutions, and the Torture Prohibition
Authors: Lesch Max
Published: June 2023

How do violations affect international norms? This article demonstrates that violations develop norms by analyzing how international institutions determine the meaning of deviant behavior and the breached norm. Decisions by courts, ad hoc tribunals, commissions of inquiry, and expert committees influence formal and informal lawmaking and drive the contested and often ambiguous development of international norms. To illustrate the impact of these norm applications and lawmaking efforts, the article compares two institutions with different mandates to oversee the international torture prohibition. In the 1960s and 1970s, the European human rights institutions defined torture for human rights law and found that Greece and the United Kingdom had violated the torture prohibition, but created ambiguity regarding the threshold of torture. In 1984, the UN Convention against Torture (CAT) adopted this definition, which was informed by earlier norm violations. In the 1990s and early 2000s, the UN Committee against Torture (CmAT) applied the torture prohibition to interrogation techniques used by Israel and the United States in counterterrorism operations. CmAT’s decisions that both countries had deviated from the norm led to General Comment No. 2 on CAT, which reaffirmed and specified the absolute and non-derogable nature of the torture prohibition.
P04 Assessment of antibiotic resistance formation predictors among medical students in developing countries
Authors: Bondaruk Iryna , Chichirelo-Konstantynovych Kiarina , Bevz Tetiana , Demchyshyn Yaroslav
Published: June 2023

Background

According to CDC (2019), antibiotic-resistant infections affect more than 2 million people. By 2030, 100 million people will die prematurely as a result of uncontrolled antibiotic use, and in 35 years, this figure will reach 300 million (BSAC, 2018). Despite of modern patient target approach to curing majority of diseases, the problem of antibiotics over usage is still urgent in middle-income countries due to non-profile prescription, absence of microbiological confirmation and the ease of availability of antibiotics.

Objectives

To investigate antibiotic usage expedience for a 1-year duration among Ukrainian and foreign medical students.

Subjects and methods

A total of 150 (Ukrainians 46%, foreigners 54%; aged 18–25 years) medical students were examined by questionnaire for antibiotic usage during last year with specification of reasons, course frequency and duration, expediency of appointment, treatment outcomes, possible reason for cancellation/replacement of antibiotic therapy and preventable usage cases.

Results

The majority of foreigners [60.5% (n = 49)] and 33.8% (n = 25) Ukrainians used antibiotics for different reasons during February 2022–January 2023 (P < 0.01). Antibiotic usage by physician’s prescription was held among 24.49% (n = 12) foreign students and 68.18% (n = 12) Ukrainian ones (P < 0.05). The frequency of antibiotic application due to positive result of bacteriological investigation was significantly lower among foreign responders: 27.27% versus 4.00% in Ukrainians (P < 0.05). In the Ukrainian students sample 36.3% (n = 8) responders predisposed to antibiotic usage for infectious condition appearance [versus 6.1% (n = 3) in the foreign sample, P < 0.01]. The frequency of ≥3 antibiotic courses per year prevailed in the foreign student group [12.25% (n = 6), P < 0.05]. The analysis of post-antibiotic adverse events found out allergic reaction in 1.2% (n = 1) in the foreign sample, diarrhoea 1.56% (n = 1) and change of antibiotic due to ineffectiveness 1.56% (n = 1) in the Ukrainian sample.

Conclusions

Possible predictors of the formation of resistance to antibiotics among young people living in developing countries, such as incorrect clinical use, lack of control over the prescription of antibiotics, ease of availability of antibiotics and as a result of self-medication, were evaluated. The prophylactic prescription of broad-spectrum antibiotics for routine procedures, such as preparation for surgical interventions and in the postoperative period, also draws attention.
P09 Non-allergist Removal of Incorrect Penicillin Allergy Labels (RIPAL) in a UK hospital
Authors: Hearsey Daniel , Elkhalifa Shuayb , Sandoe Jonathan , Wilcock Michael , Owens Rhys , Gay Bethan , Wildblood Charlotte , Mendonca Jane , Leigh Nicola , Powell Neil
Published: June 2023

Objectives

We piloted a pharmacist-led multidisciplinary penicillin allergy de-labelling (PADL) daily ward round to determine the opportunity for PADL in a UK hospital.

Methods

A daily ward round, delivered by either an antibiotic pharmacist or a junior doctor, identified adult medical and surgical patients between 7 November 2022 and 31 January 2023 with a penicillin allergy (penA) record that was preventing first-line penicillin use. An allergy history was taken before risk stratifying likelihood of future harm from penicillin re-exposure and an allergy testing method was determined [de-label on history (DOH) or after direct drug provocation testing (DDPT)]. Following successful de-label, in agreement with the responsible clinician, the antibiotic was switched to a penicillin antibiotic.

Results

Of 7214 inpatients during the study period, 1133 (15.7%) had a penA record. Of 285 allergy histories taken, 105 (36.8%) met high-risk criteria, 45 (15.8%) met low-risk criteria eligible for DOH, 73 (25.6%) met low-risk criteria eligible for DDPT and we were unable to obtain a history from 62 (21.8%) patients. Of 45 low-risk patients eligible for DOH, 40 (88.9%) were de-labelled of which 24 (53.3%) were switched to a penicillin antibiotic. Of 73 patients with a low-risk allergy history eligible for DOC, 16 (21.9%) received DDPT, of which nine were switched to a penicillin antibiotic to complete their antibiotic course. Two DOH patients experienced harm (thrush within the first 5 days and delayed skin reaction after day 5), none of the DPTs had a reaction by day 5. The switches resulted in 170 DDDs of penicillin use (predominantly amoxicillin) and reduced alternative antibiotic use by 174 DDDs (predominantly meropenem and levofloxacin).

Conclusions

Penicillin allergy de-labelling patient pathway delivered by pharmacists and junior doctors was safe and effective and well accepted by patients and the wider clinical teams. Further work is required to optimize and streamline these patient pathways to maximize patient and health system benefit.
P10 Impact of miniaturization and early readout on antimicrobial susceptibility tests
Authors: Needs Sarah , Hayward Jessica , Kidd Stephen , Edwards Al
Published: June 2023

Background

New technologies offer the promise of faster, more accessible antibiotic susceptibility testing. UK policy includes the development and introduction of innovative diagnostics to tackle antimicrobial resistance, and whilst many new technologies are emerging, we still have limited evidence of their performance. Many of these emerging technologies are changing two core aspects of antimicrobial susceptibility tests (AST). Firstly, using microfluidic platforms to miniaturize standard antibiotic susceptibility testing and secondly measuring susceptibility at earlier timepoints, here, we report a comprehensive assessment of 1-mL volume broth microdilution with an early endpoint readout, proving that miniaturization and earlier timepoints of conventional antibiotic susceptibility testing is feasible and accurate.

Methods

The test measures bacterial growth in 1-mL capillaries in the presence of the metabolic dye resazurin. All other aspects of the test remain standard. Images of the capillaries are taken every 5 minutes over 18 h to determine accuracy at different timepoints during incubation at 37°C. Over a total of 3 sites in the UK, Spain and Thailand, we have tested 367 isolates from clinical samples for 8–17 antibiotics.

Results

Preliminary data shows that for 99 Gram-negative isolates tested in Thailand, after 6-h incubation, accuracy for antibiotics is as follows: cefotaxime 96%, ceftazidime 92%, meropenem 93%, amikacin 94%, amoxicillin–clavulanic acid 79%, cefuroxime 97%, cefoxitin 80%, ciprofloxacin 84%, gentamicin 93% and trimethoprim 97%. Further testing is ongoing, and isolates from urine samples are currently being collected from Basingstoke and North Hampshire hospital to expand the type of organism tested.

Conclusions

Unlike many microfluidic systems, the dip and test microcapillary–based broth microdilution test is manufactured in bulk, allowing rapid and testing of large sample sets with minimal investment. An understanding of the effect of miniaturization is vital to developers of microfluidic phenotypic antibiotic susceptibility tests and can provide confidence in emerging systems.
P13 Cost effectiveness of point of care diagnostics for AMR: a systematic review
Authors: Tolley Abraham , Bansal Akhil , Murerwa Becca
Published: June 2023

Objectives

Antimicrobial resistance (AMR) is a major threat to global health and is driven partly by overprescription of antibiotics. Point-of-care tests (POCTs) can reduce antibiotic prescribing by distinguishing different types of infections and the sensitivities of pathogens to antimicrobials. Although evidence for their clinical efficacy is mixed, they may be highly cost-effective interventions when their benefits in reducing the burden of AMR are considered. We aimed to systematically evaluate the cost effectiveness of different POCTs in reducing AMR for the first time to inform national and global health policies.

Methods

A systematic review was conducted in line with the PRISMA framework, and the protocol was registered on PROSPERO. MEDLINE, PubMed, EMBASE, Cochrane Library and Google Scholar were searched from January 2000 to November 2022 for studies that (i) were trial- or model-based economic evaluations, (ii) focused on POCTs aimed at reducing AMR or inappropriate antimicrobial prescription, (iii) included a cost-benefit metric and (iv) were original research written in English with full text available. Methodological quality was assessed using the Consensus of Health Economic Criteria.

Results

157 studies were retrieved of which 20 were included after screening. These included both trial (n = 9) and modelling-based (n = 11) evaluations. Most focused on POCTs for respiratory infections (n = 9) with sexually transmitted infections and febrile illness other common conditions evaluated. A majority of studies utilized C-reactive protein POCTs (n = 11) with others utilizing pathogen-specific PCR tests or procalcitonin. Most evaluated the cost effectiveness of POCTs at reducing antimicrobial prescribing, with only 3 studies considering the societal cost of AMR. Most studies found that POCTs reduced antibiotic use, but with varying cost effectiveness: 16 studies showed cost efficacy by the threshold or other standards stipulated by the study, with POCTs for group B streptococcus and urinary tract infections notably not found to be cost effective. The reporting and methodological quality of the included studies was mixed: good (4), moderate (13) and low (3).

Conclusions

There is limited research on the cost effectiveness of POCTs in reducing AMR, and most studies do not account for the wider societal costs of AMR. Current forecasts estimate that AMR will cause 10 million deaths and cost the world 100 trillion USD per year in 2050: consequently, it is vital that evaluations of POCTs include the significant benefits from reducing AMR additional to the short-term benefits of avoided antibiotic prescriptions. Given the rising burden of AMR, such interventions merit further evaluation and integration into healthcare policy.
P14 Surgical source control and colistin therapy for the management of osteomyelitis due to Pseudomonas aeruginosa with difficult-to-treat resistance
Authors: Nageshwaran V , Ferguson J , Ramsden A , Barrett L , Scarborough M , Wangrangsimakul T , Morgan M , Oakley S , Young B C , Stoesser N
Published: June 2023

Patient

A 45-year-old man from Lagos, Nigeria, now living in the UK, presented to his local hospital with purulent discharge from his knee. During a road traffic accident in 2019, he had sustained open fractures of his femur and tibia. These required surgical fixation and he underwent four surgeries over a 10-month period in Nigeria. He was reportedly on antibiotics throughout this period. In early 2022, he noticed discharge from the knee and was referred to the Bone Infection Unit in Oxford. On examination, left leg shortening and a sinus on the anterior proximal tibia were noted. Knee flexion was reduced to 30 degrees. He was otherwise systemically well. PET-CT revealed two areas of avidity, supporting the clinical diagnosis of fracture-related infection adjacent to a retained tibial plate.

Treatment

The patient underwent removal of the tibial plate, excision of infected bone, insertion of local antibiotic carrier (Cerament G with vancomycin added) and a medial gastrocnemius flap with split skin grafting. Five out of five intra-operative samples were culture positive for Pseudomonas aeruginosa, with NDM metallo-β-lactamase detected. This was resistant to ceftazidime, meropenem, piperacillin/tazobactam, gentamicin, tobramycin, amikacin, ciprofloxacin, ceftazidime/avibactam, imipenem/cilastatin/relebactam, ceftolozane/tazobactam and cefiderocol. The organism had an aztreonam MIC of 16 mg/mL and a colistin MIC of 2 mg/mL. The patient also had MRSA isolated from all intra-operative samples. Following multidisciplinary team discussion, he was started on aztreonam 2 g QDS and colistin loading with 9 million IU followed by 4.5 million IU BD for the P. aeruginosa and doxycycline 100 mg BD for the MRSA. After 8 days of therapy, he developed a symmetrical body rash, which was felt to be a delayed hypersensitivity reaction to aztreonam and resolved when aztreonam was stopped. He was subsequently treated with colistin monotherapy for 6 weeks via OPAT. Whilst on this treatment, his renal function was monitored regularly with appropriate dose reductions because of renal impairment. Follow-up at 9 months demonstrates good recovery with no pain or symptom recurrence.

Conclusions

This case illustrates the challenges of managing fracture-related infections with extensively drug-resistant organisms and the importance of multi-disciplinary input. Drug-resistant infections requiring prolonged courses of antibiotics can be successfully managed using an OPAT service. Finally, this case emphasizes the importance of understanding global patterns of antimicrobial resistance and stewardship to identify cases that are at risk of being infected with drug-resistant bacteria especially where there may be long intervals between establishment of the infection and presentation to healthcare services.
P29 Outcomes by baseline pathogen and susceptibility in the ReSTORE Phase 3 trial of rezafungin once weekly compared with caspofungin once daily in patients with candidaemia and/or invasive candidiasis
Authors: Thompson G R , Soriano A , Cornely O A , Kullberg B J , Kollef M , Vazquez J A , Das A F , Locke J B , Sandison T , Pappas P G
Published: June 2023

Background

Rezafungin is a next-generation, once-weekly echinocandin in development for treatment of candidaemia and invasive candidiasis (IC), and for prevention of invasive fungal diseases caused by Candida, Aspergillus, and Pneumocystis in allogeneic blood and marrow transplant recipients (Figure 1). ReSTORE (NCT03667690) is a global, double-blind, double-dummy, 1:1 randomized, controlled, Phase 3 non-inferiority trial that evaluated the efficacy and safety of rezafungin once weekly (QWk) versus caspofungin once daily (QD) in patients with candidaemia and/or IC. This analysis of the completed ReSTORE trial was conducted to evaluate outcomes by baseline pathogen and susceptibility.

Methods

In ReSTORE, adults (≥18 y) with systemic signs and mycological confirmation of candidaemia and/or IC received either rezafungin QWk (400 mg Week 1, then 200 mg QWk) or caspofungin QD for ≥14 days (up to 4 weeks) with optional oral fluconazole step-down in the caspofungin arm. The primary endpoints were global cure at day (D)14 (per Data Review Committee confirmation of investigator-assessed clinical cure [and radiological cure for IC) + mycological eradication]) and all-cause mortality (ACM) at D30 (Figure 2). Secondary endpoints included mycological eradication at D14. For this analysis, D14 global cure and mycological eradication by treatment group were analysed by Candida species and in vitro susceptibility at baseline (CLSI broth microdilution MIC values; M27 Ed4) (Figure 3).

Results

A total of 204 Candida isolates were recovered in 187 patients across both treatment groups. Of the 204 isolates, Candida albicans was the most common species, followed by Candida glabrata, Candida tropicalis, and Candida parapsilosis; 61% of all baseline isolates were non-albicans Candida (Figure 3). The rates of D14 global cure and mycological eradication by pathogen are shown in Tables 1 and 2. Overall, outcomes by Candida species and MIC did not appear to be affected by MIC values for either rezafungin or caspofungin (Table 3).

Conclusions

Rezafungin was efficacious across multiple Candida species in the Phase 3 ReSTORE trial that demonstrated non-inferiority of rezafungin to caspofungin. There was no clear correlation between increased MIC values and clinical outcomes.
P36 Using the Australian National Antimicrobial Prescribing Survey portal (NAPS) to benchmark antibiotic prescribing within an Integrated Care Board (ICB): a pilot point prevalence survey (PPS) of two NHS Trusts
Authors: Jones Nicola , Ng Bee Yean , O’Riordan Bernadette , Ahmadi Aarash , O’Driscoll Jean , Brandish Claire
Published: June 2023

Background

PPS is useful in evaluating volume and appropriateness of antimicrobial prescribing to guide specific antimicrobial stewardship (AMS) interventions. Integrated care systems enable collaboration within an ICB and benchmarking of antimicrobial prescribing in constituent trusts to identify disparities and learn from sharing best practice. NAPS is a web-based qualitative auditing platform which is used to conduct an annual Australia-wide PPS. To assess the suitability of NAPS in benchmarking antimicrobial prescribing practices, we piloted the NAPS platform in the acute admission ward areas in two NHS Trusts within an ICB.

Methods

In OUHFT, admissions to 2 acute medicine wards on a single day were extracted using the Cerner electronic prescribing system. Antimicrobial prescriptions were anonymized, reviewed using NAPS protocol and uploaded to the NAPS platform. In BHT, antimicrobial prescriptions on 2 admission wards were collected manually using the NAPS parameters and audit standards and entered directly into Excel®. Ethical approval was not required due to the anonymized nature of this audit.

Results

A total of 124 patients at OUHFT and 53 patients at BHT were included. The proportion of patients prescribed antimicrobials varied, with a prevalence of 23% (n = 29) at OUHFT and 54% (n = 28) at BHT. The total number of antimicrobial prescriptions was approximately 40 per trust. Compliance with guidelines for OUHFT and BHT (88% versus 83%) and stewardship appropriateness (73% versus 80%) were similar. The main indication for antimicrobials was pneumonia. The most common reasons for inappropriateness were ‘incorrect duration’ and ‘spectrum too broad’. The most prescribed antimicrobials differed, with co-amoxiclav and amoxicillin (43%) at OUHFT and metronidazole and clarithromycin (24%) at BHT. Non-compliance with guidelines was frequently associated with the use of doxycycline and co-amoxiclav (47%) at OUHFT and amoxicillin and piperacillin/tazobactam (72%) at BHT.

Conclusions

Benchmarking of antimicrobial prescribing was possible as both PPSs were conducted using the NAPS parameters and standards. Focusing efforts on antibiotic prescribing for pneumonia, the use of broad-spectrum antimicrobials and reducing duration of courses will be taken forward as a key focus for AMS efforts. NAPS is a suitable tool for benchmarking, sharing best practice and facilitating discussion of AMS interventions across an ICB. This model should be considered as a template for national benchmarking of antimicrobial prescribing.
P38 The AMR Patient Shield (APS) project: patient empowerment in the fight against antimicrobial resistance
Authors: Gupta Aman , Famokunwa Dele , Ashfield Tom , Amos James , Cooray Mineli
Published: June 2023

Background

Pfizer and the Patient’s Association (PA) collaborated on the AMR Patient Shield project, which aimed to explore the role of patients in responding to antimicrobial resistance (AMR) and empower them to work with their clinicians to support appropriate use of antibiotics in their care. The project had two phases, with a focus on engagement and education of patients, culture change and education of healthcare professionals (HCPs).

Methods

In Phase I, patients were convened for a patient advisory board in 2021, and Phase II involved two subsequent resource co-creation workshops in 2022. PA recruited nine patients for each phase, and the meetings were co-facilitated by PA and Pfizer medical representatives. Two antimicrobial pharmacists also served as advisors in Phase II to provide input on the applicability of the proposed resources within the clinical setting.

Outcomes

The project resulted in a range of tailored resources for both patients and HCPs, aimed at supporting patients to also become stewards of appropriate antibiotic use. These resources included educational leaflets, a template patient-held microbiology record, an HCP antibiotic consent checklist, and audio-visual content. The resources developed for patients improved their literacy on AMR at both the population and individual health levels, enabling them to utilize the incorporated tools for shared decision-making conversations with their HCPs. The content designed specifically for HCPs aimed to improve their ability to obtain informed consent, maintain accurate records and support clinical decision making when prescribing antimicrobials.

Conclusions

The AMR Patient Shield project highlights the shift from working for patients to working with patients, emphasizing the vital importance of shared decision making between HCPs, industry, policy makers and patients in the stewardship agenda. By involving patients as active partners in the AMR response strategies, the project aims to empower them to participate in their own care, improve their understanding of AMR and engage in SDM discussions with their clinicians. In conclusion, the AMR Patient Shield project, a collaboration between Pfizer and the Patient’s Association, has resulted in tailored resources for patients and HCPs to support their engagement in appropriate antibiotic use. These resources aim to improve patient literacy on AMR and enhance HCPs’ ability to obtain informed consent and exercise clinical judgement. The project highlights the importance of shared decision making and collaboration among stakeholders in addressing AMR, placing patients as fundamental partners in the collective response to this global health challenge.
Whole genome sequencing of multidrug resistant Enterobacterales identified in children and their household members within Siem Reap, Cambodia
Authors: Singh Shweta R , Tang Cheng Yee , Mao Bunsoth , Soeng Sona , Ling Clare L , Teo Jocelyn Qi-Min , Vonthanak Saphonn , Turner Paul , Hsu Li Yang , Ong Rick Twee-Hee
Published: June 2023

Objectives

To explore the association of recent hospitalization and asymptomatic carriage of multidrug-resistant Enterobacterales (MDRE) and determine the prevailing strains and antibiotic resistance genes in Siem Reap, Cambodia using WGS.

Methods

In this cross-sectional study, faecal samples were collected from two arms: a hospital-associated arm consisted of recently hospitalized children (2–14 years), with their family members; and a community-associated arm comprising children in the matching age group and their family members with no recent hospitalization. Forty-two families in each study arm were recruited, with 376 enrolled participants (169 adults and 207 children) and 290 stool specimens collected from participants. The DNA of ESBL- and carbapenemase-producing Enterobacterales cultured from the faecal samples was subject to WGS on the Illumina NovaSeq platform.

Results

Of the 290 stool specimens, 277 Escherichia coli isolates and 130 Klebsiella spp. were identified on CHROMagar ESBL and KPC plates. The DNA of 276 E. coli (one isolate failed quality control test), 89 Klebsiella pneumoniae, 40 Klebsiella quasipneumoniae and 1 Klebsiella variicola was sequenced. CTX-M-15 was the most common ESBL gene found in E. coli (n = 104, 38%), K. pneumoniae (n = 50, 56%) and K. quasipneumoniae (n = 16, 40%). The prevalence of bacterial lineages and ESBL genes was not associated with any specific arm.

Conclusions

Our results demonstrate that MDRE is likely to be endemic within the Siem Reap community. ESBL genes, specifically blaCTX-M, can be found in almost all E. coli commensals, indicating that these genes are continuously propagated in the community through various unknown channels at present.
Procurement of patient medical records from multiple health care facilities for public health research: feasibility, challenges, and lessons learned
Authors: McMahon James M , Brasch Judith , Podsiadly Eric , Torres Leilani , Quiles Robert , Ramos Evette , Crean Hugh F , Haberer Jessica E
Published: June 2023

Objectives

Studies that combine medical record and primary data are typically conducted in a small number of health care facilities (HCFs) covering a limited catchment area; however, depending on the study objectives, validity may be improved by recruiting a more expansive sample of patients receiving care across multiple HCFs. We evaluate the feasibility of a novel protocol to obtain patient medical records from multiple HCFs using a broad representative sampling frame.

Materials and Methods

In a prospective cohort study on HIV pre-exposure prophylaxis utilization, primary data were collected from a representative sample of community-dwelling participants; voluntary authorization was obtained to access participants’ medical records from the HCF at which they were receiving care. Medical record procurement procedures were documented for later analysis.

Results

The cohort consisted of 460 participants receiving care from 122 HCFs; 81 participants were lost to follow-up resulting in 379 requests for medical records submitted to HCFs, and a total of 343 medical records were obtained (91% response rate). Less than 20% of the medical records received were in electronic form. On average, the cost of medical record acquisition was $120 USD per medical record.

Conclusions

Obtaining medical record data on research participants receiving care across multiple HCFs was feasible, but time-consuming and resulted in appreciable missing data. Researchers combining primary data with medical record data should select a sampling and data collection approach that optimizes study validity while weighing the potential benefits (more representative sample; inclusion of HCF-level predictors) and drawbacks (cost, missing data) of obtaining medical records from multiple HCFs.
Enhancing feature selection with GMSMFO: A global optimization algorithm for machine learning with application to intrusion detection
Authors: Hussein Nazar K , Qaraad Mohammed , Amjad Souad , Farag M A , Hassan Saima , Mirjalili Seyedali , Elhosseini Mostafa A
Published: June 2023

The paper addresses the limitations of the Moth-Flame Optimization (MFO) algorithm, a meta-heuristic used to solve optimization problems. The MFO algorithm, which employs moths' transverse orientation navigation technique, has been used to generate solutions for such problems. However, the performance of MFO is dependent on the flame production and spiral search components, and the search mechanism could still be improved concerning the diversity of flames and the moths' ability to find solutions. The authors propose a revised version called GMSMFO, which uses a Novel Gaussian mutation mechanism and shrink MFO to enhance population diversity and balance exploration and exploitation capabilities. The study evaluates the performance of GMSMFO using the CEC 2017 benchmark and 20 datasets, including a high-dimensional intrusion detection system dataset. The proposed algorithm is compared to other advanced metaheuristics, and its performance is evaluated using statistical tests such as Friedman and Wilcoxon rank-sum. The study shows that GMSMFO is highly competitive and frequently superior to other algorithms. It can identify the ideal feature subset, improving classification accuracy and reducing the number of features used. The main contribution of this research paper includes the improvement of the exploration/exploitation balance and the expansion of the local search. The ranging controller and Gaussian mutation enhance navigation and diversity. The research paper compares GMSMFO with traditional and advanced metaheuristic algorithms on 29 benchmarks and its application to binary feature selection on 20 benchmarks, including intrusion detection systems. The statistical tests (Wilcoxon rank-sum and Friedman) evaluate the performance of GMSMFO compared to other algorithms. The algorithm source code is available at https://github.com/MohammedQaraad/GMSMFO-algorithm.
Simulation to investigate site-based monitoring of pest insect species for trade
Authors: van Klinken Rieks D , Gladish Daniel W , Manoukis Nicholas C , Caley Peter , Hill Matthew P
Published: June 2023

Pest insect surveillance using lures is widely used to support market access requirements for traded articles that are hosts or carriers of quarantine pests. Modeling has been used extensively to guide the design of surveillance to support pest free area claims but is less commonly applied to provide confidence in pest freedom or low pest prevalence within sites registered for trade. Site-based surveillance typically needs to detect pests that are already present in the site or that may be entering the site from surrounding areas. We assessed the ability of site-based surveillance strategies to detect pests originating from within or outside the registered site using a probabilistic trapping network simulation model with random-walk insect movement and biologically realistic parameters. For a given release size, time-dependent detection probability was primarily determined by trap density and lure attractiveness, whereas mean step size (daily dispersal) had limited effect. Results were robust to site shape and size. For pests already within the site, detection was most sensitive using regularly spaced traps. Perimeter traps performed best for detecting pests moving into the site, although the importance of trap arrangement decreased with time from release, and random trap placement performed relatively well compared to regularly spaced traps. High detection probabilities were achievable within 7 days using realistic values for lure attractiveness and trap density. These findings, together with the modeling approach, can guide the development of internationally agreed principles for designing site-based surveillance of lure-attractant pests that is calibrated against the risk of non-detection.
Human Rights Beyond the Colonial Imagination: Legal Empowerment and Techniques of Delegitimation
Authors: Ilyés Emese , Chiponda Melania , Dhital Sukti , Satterthwaite Meg , Badkur Aakanksha , Gutierrez Antonio , Carson Bethany , Mustafa Dyari , Mesel Felipe , Feruglio Francesca , Mushin Noor , Chitalkar Poorvi , Sen Shreya , Kakuru Tim , Weerachat Tom , Walton Tyler
Published: June 2023

Community-based and participatory methods are often marginalized within institutions of power. In this article, we—a group of community advocates, lawyers, scholars, and researchers from across the globe including Thailand, India, Uganda, Zimbabwe, Italy, Iraq, Argentina, the UK, Puerto Rico, and the United States—have collectively gathered ways that community based, participatory legal empowerment research has been delegitimized across these contexts, and offer practical strategies to break out of this white supremacist colonial imagination and interrupt and respond to these instances of silencing and erasure. Our gatherings enable us to bring to life the rich particulars of each of our unique contexts and through this richness begin to see how larger dynamics span the globe. The micro illuminates the mechanics of the macro. This critical analysis that is possible in such a participatory space allowed us to identify these strategies of delegitimation that we were experiencing despite our very different positionalities and histories. These techniques of delegitimation fall into three broad themes: using traditional research as defence, attacking the credibility of communities including denying their humanity, and acts of self-invalidation. These techniques, whether enacted by donors, companies, government agencies, or academic institutions, seek to disempower the lived experiences of community members involved in legal empowerment. By cataloguing these experiences we hope to better understand techniques of silencing and oppression, and to trace the ways that systems of power reinforce their standing through these immediate and interpersonal responses to the voice of the collective.
Confidentiality, public interest, and the human right to science: when can confidential information be used for the benefit of the wider community?
Authors: Dove Edward S
Published: June 2023

This article explores whether the human right to science can support the public interest as a legal basis to use and disclose confidential information. The contextual focus is scientific research; the jurisdictional focus is England. The human right to science, as reflected in the Universal Declaration of Human Rights (Article 27) and the International Covenant on Economic, Social and Cultural Rights (Article 15), hitherto has not been invoked in support of a public interest basis for lawful disclosure, but the argument is made herein that there may be scope to develop this jurisprudentially. On grounds of both law and policy, and in line with the underlying rationale of recent UK Government deployment of ‘COPI Notices’ for lawful use of confidential patient information in the course of the COVID-19 pandemic, I contend that the human right to science may well serve as a valuable juridical buttress to an overriding public interest justification to lawfully share confidential information. However, this could occur only in restricted circumstances where the public interest is clearly manifest, namely studies researching serious, imminent health threats to the general population that rely on confidential information accessed outside of existing statutory gateways, and not more routine scientific endeavors.
Spotlight on Coenzyme Q10 in scopolamine-induced Alzheimer’s disease: oxidative stress/PI3K/AKT/GSK 3ß/CREB/BDNF/TrKB
Authors: Abuelezz Sally A , Hendawy Nevien
Published: June 2023

Objectives

Excess amyloid beta (Aβ) and oxidative stress (OS) are inextricable hallmarks of the neuronal damage associated Alzheimer’s disease. Aβ-induced cognitive and memory dysfunctions are mediated through different signalling pathways as phosphatidylinositol-3-kinase (PI3K) and their downstream intermediates including protein-kinase-B, known as Akt, glycogen-synthase-kinase-3β (GSK-3β), cAMP-response-element-binding-protein (CREB), brain-derived-neurotrophic factor (BDNF) and tropomyosin-related-kinase receptor-B (TrKB). The current work aims to investigate the protective potentials of CoQ10 against scopolamine (Scop)-induced cognitive disability and the contribution of PI3K/Akt/GSK-3β/CREB/BDNF/TrKB in the neuroprotection effects.

Methods

The chronic co-administration of CQ10 (50, 100 and 200 mg/kg/day i.p.) with Scop in Wistar rats for 6 weeks were assayed both behaviourally and biochemically.

Key findings

CoQ10 ameliorated the Scop-induced cognitive and memory defects by restoring alterations in novel object recognition and Morris water maze behavioural tests. CoQ10 favourably changed the Scop-induced deleterious effects in hippocampal malondialdehyde, 8-hydroxy-2ʹ deoxyguanosine, antioxidants and PI3K/Akt/GSK-3β/CREB/BDNF/TrKB levels.

Conclusions

These results exhibited the neuroprotective effects of CoQ10 on Scop-induced AD and revealed its ability to inhibit oxidative stress, amyloid deposition and to modulate PI3K/Akt/GSK-3β/CREB/BDNF/TrKB pathway.
Comparative dosimetric and radiobiological assessment of left-sided whole breast and regional nodes with advanced radiotherapy techniques
Authors: Huang Yuling , Gong Changfei , Luo Mingming , Yuan Xingxing , Ding Shenggou , Wang Xiaoping , Zhang Yun
Published: June 2023

The aim of this study was to analyze the dosimetric and radiobiologic differences of the left-sided whole breast and regional nodes in intensity-modulated radiotherapy (IMRT), volume-modulated arc therapy (VMAT), and helical tomotherapy (HT).  The IMRT, VMAT, and HT plans in this study were generated for thirty-five left-sided breast cancer patients after breast-conserving surgery (BCS). The planning target volume (PTV) included the whole breast and supraclavicular nodes. PTV coverage, homogeneity index (HI), conformity index (CI), dose to organs at risk (OARs), secondary cancer complication probability (SCCP), and excess absolute risk (EAR) were used to evaluate the plans. Compared to IMRT, the VMAT and HT plans resulted in higher PTV coverage and homogeneity. The VMAT and HT plans also delivered a lower mean dose to the ipsilateral lung (9.19 ± 1.36 Gy, 9.48 ± 1.17 Gy vs. 11.31 ± 1.42 Gy) and heart (3.99 ± 0.86 Gy, 4.48 ± 0.62 Gy vs. 5.53 ± 1.02 Gy) and reduced the V5Gy, V10Gy, V20Gy, V30Gy, and V40Gy of the ipsilateral lung and heart. The SCCP and EAR for the ipsilateral lung were reduced by 3.67%, 3.09% in VMAT, and 22.18%, 19.21% in HT, respectively. While were increased for the contralateral lung and breast. This study showed that VMAT plans provide a more homogeneous dose distribution to the PTV, minimizing exposure to ipsilateral structures and significantly reducing SCCP and EAR, and slightly increasing dose to contralateral structures. Overall, the VMAT plan can be considered a beneficial technique for BCS patients whose PTV includes the whole breast and regional nodes.
Strategic two-sample test via the two-armed bandit process
Authors: Chen Zengjing , Yan Xiaodong , Zhang Guodong
Published: June 2023

This study aims to improve the power of two-sample tests by analysing whether the difference between two population parameters is larger than a prespecified positive equivalence margin. The classic test statistic treats the original data as exchangeable, while the proposed test statistic breaks the structure and proposes employing a two-armed bandit process to strategically integrate the data and thus a strategy-specific test statistic is constructed by combining the classic CLT with the law of large numbers. The developed asymptotic theory is investigated by using nonlinear limit theory in a larger probability space and relates to the ‘strategic CLT’ with a clearly defined density function. The asymptotic distribution demonstrates that the proposed statistic is more concentrated under the null hypothesis and less concentrated under the alternative than the classic CLT, thereby enhancing the testing power. Simulation studies provide supporting evidence for the theoretical results and portray a more powerful performance when using finite samples. A real example is also added for illustration.