bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive stability analysis of 13 β-lactams and β-lactamase inhibitors in
in vitro
media, and novel supplement dosing strategy to mitigate thermal drug degradation
Authors: Zhou Jieqiang , Qian Yuli , Lang Yinzhi , Zhang Yongzhen , Tao Xun , Moya Bartolome , Sayed Alaa R. M. , Landersdorfer Cornelia B. , Shin Eunjeong , Werkman Carolin , Smith Nicholas M. , Kim Tae Hwan , Kumaraswamy Monika , Shin Beom Soo , Tsuji Brian T. , Bonomo Robert A. , Lee Richard E. , Bulitta Jürgen B. 
Published: February 2024

ABSTRACT

Non-clinical antibiotic development relies on
in vitro
susceptibility and infection model studies. Validating the achievement of the targeted drug concentrations is essential to avoid under-estimation of drug effects and over-estimation of resistance emergence. While certain β-lactams (e.g., imipenem) and β-lactamase inhibitors (BLIs; clavulanic acid) are believed to be relatively unstable, limited tangible data on their stability in commonly used
in vitro
media are known. We aimed to determine the thermal stability of 10 β-lactams and 3 BLIs via LC-MS/MS in cation-adjusted Mueller Hinton broth at 25 and 36°C as well as agar at 4 and 37°C, and in water at −20, 4, and 25°C. Supplement dosing algorithms were developed to achieve broth concentrations close to their target over 24 h. During incubation in broth (pH 7.25)/agar, degradation half-lives were 16.9/21.8 h for imipenem, 20.7/31.6 h for biapenem, 29.0 h for clavulanic acid (studied in broth only), 23.1/71.6 h for cefsulodin, 40.6/57.9 h for doripenem, 46.5/64.6 h for meropenem, 50.8/97.7 h for cefepime, 61.5/99.5 h for piperacillin, and >120 h for all other compounds. Broth stability decreased at higher pH. All drugs were ≥90% stable for 72 h in agar at 4°C. Degradation half-lives in water at 25°C were >200 h for all drugs except imipenem (14.7 h, at 1,000 mg/L) and doripenem (59.5 h). One imipenem supplement dose allowed concentrations to stay within ±31% of their target concentration. This study provides comprehensive stability data on β-lactams and BLIs in relevant
in vitro
media using LC-MS/MS. Future studies are warranted applying these data to antimicrobial susceptibility testing and assessing the impact of β-lactamase-related degradation.
Genome sequences of
Colletotrichum eleusines
and
C. echinochloae
: two pathogens from
Poaceae
weeds
Authors: Gu Qiongnan , Chu Shihai , Huang Qichao , Li Lin , Chen Anan , Hsiang Tom , Li Ruhai 
Published: February 2024

ABSTRACT

We present two whole-genome sequences of
Colletotrichum
strains which were isolated from
Eleusine indica
and
Echinochloa crus-galli
using Nanopore and Illumina technologies, as part of screening for potential mycoherbicide. The genome sequences will provide important genetic information and will be useful for further research into secondary metabolites of
Colletotrichum
.
Submarine volcanism along shallow ridges did not drive Cryogenian cap carbonate formation
Authors: Dutkiewicz Adriana , Müller R. Dietmar 
Published: February 2024

Abstract
The termination of Neoproterozoic “Snowball Earth” glaciations is marked globally by laterally extensive neritic cap carbonates directly overlying glacial diamictites. The formation of these unique deposits on deglaciation calls for anomalously high calcium carbonate saturation. A popular mechanism to account for the source of requisite ocean alkalinity is the shallow-ridge hypothesis, in which initial spreading ridges surrounding fragments of Rodinia, assumed to be dominated by volcanic margins, were formed at sea level. The shallow ridges are inferred to have promoted widespread deposition and alteration of glassy hyaloclastite—a source of alkalinity. We test this hypothesis by quantifying the prevalence of shallow ridges along Pangea's passive continental margins, and by assessing Neoproterozoic reconstructions of tectonic plates. We find that the most frequently occurring depth range for incipient mid-ocean ridges is 2.1 ± 0.4 km. Ridges with initial elevations of approximately sea level are rare and have anomalous crustal thicknesses &gt;14 km that only occur proximal to large igneous provinces (LIPs). Hyaloclastite is uncommon on mid-ocean ridges as it is generally restricted to water depths of &lt;200 m for tholeiitic basalts, instead forming mostly on intraplate seamounts. Additionally, ocean drilling recently found hyaloclastite to be insignificant along the outer Vøring Plateau (offshore Norway)—an exemplar of a volcanic margin. Reconstructions of Rodinia and associated LIPs demonstrate that volcanic margins potentially hosting minor hyaloclastites were scarce during the late Neoproterozoic. We conclude that the shallow-ridge hypothesis fails to explain the formation of cap carbonates and suggest that other mechanisms such as enhanced continental weathering may be largely responsible.
Association between home meal preparers and salt intake in haemodialysis patients: a cross-sectional study
Authors: Uchida Haruna , Hidaka Tomoo , Endo Shota , Kasuga Hideaki , Masuishi Yusuke , Kakamu Takeyasu , Fukushima Tetsuhito 
Published: February 2024

ObjectivesThis study aimed to examine the association between home meal preparer and salt intake among haemodialysis patients, including daily dietary status. We hypothesised that salt intake is higher among individuals who rely on meal preparation from others than those who prepare meals by themselves.DesignCross-sectional study.SettingTwo medical facilities in Fukushima Prefecture, Japan.Participants237 haemodialysis outpatients who visited one of the medical facilities between February 2020 and August 2021 and were diagnosed with anuria, defined as urination of <100 mL/day, were the potential participants of the present study. Finally, 181 participants (131 male and 50 female) were included in the analysis.Outcome measureSalt intake amount was calculated from the results of predialysis and postdialysis blood draws, using Watson’s formula based on predialysis weight, predialysis serum sodium level, postdialysis weight and serum sodium level at the end of dialysis.ResultsSalt intake was significantly higher in participants who relied on meal preparation from others (‘relying on others’) than those who prepared meals by themselves (‘self-prepared’) (B=1.359; 95% CI: 0.495 to 2.222). No statistical difference was found between individuals who ate out or ate takeout (‘outsourcing’) and those who prepared their own meals (‘self-prepared’). These results were robust after adjustment for confounding factors.ConclusionsThe present study revealed an association between self-preparation of meals at home and reduced salt intake among dialysis patients. Our findings suggest that whoever is the home meal preparer is possibly a social determinant of salt intake. To improve the prognosis of haemodialysis patients, actively reaching out to the family and assessing their social environment, such as identifying the home meal preparer and, if the patient relies on others for meal preparation, conducting nutritional/dietary guidance for that person, are effective in enhancing salt reduction.
Adaptive coping strategies among individuals living with long-term chikungunya disease: a qualitative study in Curaçao
Authors: Doran Churnalisa , Duits Ashley J , Gerstenbluth Izzy , Tami Adriana , Bailey Ajay 
Published: February 2024

ObjectiveLong-term chikungunya disease is characterised by persistent rheumatic symptoms following chikungunya virus infection. As there is no specific treatment available, affected individuals need strategies to adapt. However, research on these is scarce. This study aimed to explore which adaptive coping strategies are employed to manage persistent rheumatic symptoms in daily life.SettingThe study was conducted in Curaçao.Design and participantsAn explorative qualitative study was conducted between September and October 2020, among a purposive sample of adults, 19 women and 4 men affected by long-term chikungunya disease. In-depth interviews were semi-structured and transcribed verbatim. The data were analysed using inductive thematic analysis.ResultsThe disease duration for all participants ranged between 68 and 74 months (6 years). In narrating their experiences of coping with long-term chikungunya disease, four themes were identified: (1) learning to live with the disease; (2) resilience for dealing with pain; (3) maintaining positive self-image and attitude; and (4) coping through spirituality.ConclusionTo live with long-term chikungunya disease with dignity in spite of physical pain and discomfort, participants tried to retain a sense of control of oneself and one’s lives, to not let the disease take over, focusing on the positive in their lives, and finding strength and remain hopeful. Interventions such as cognitive–behavioural therapy and mindfulness exercises may be effective in strengthening or regain affected individual’s sense of competence and control by fostering adaptive coping skills and resilience. Subsequently, these interventions may improve health-related quality of life when rheumatic symptoms persist following chikungunya virus infection.
Instruments and indicators for assessing organisational food environments: a scoping review protocol
Authors: Azevedo Ana Beatriz Coelho de , Curioni Cintia Chaves , Bandoni Daniel Henrique , Canella Daniela Silva 
Published: February 2024

IntroductionMany studies have explored the food environment to characterise it and understand its role in food practices. Assessment of the organisational food environment can contribute to the development of more effective interventions to promote adequate and healthy eating. However, few instruments and indicators have been developed and validated for assessing this type of setting. The systematisation of those can be useful to support the planning of future assessments and the development of wide-ranging instruments. This study aims to conduct a scoping review to systematise evidence on instruments and indicators for assessing organisational food environments.Methods and analysisThis scoping review was planned according to the methodological framework for scoping reviews proposed by Arksey and O’Malley and subsequently enhanced by Levacet al. For the report of the review, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses—Extension for Scoping Reviews (PRISMA-ScR) checklist and guidelines will be used. The search will be conducted using PubMed, Embase, Web of Science, PsycINFO, Scopus and Google Scholar databases. The studies to be included were required to have been published in peer-reviewed journals since January 2005. No geographical, population or language restrictions will be applied given the desired breadth of the review. Two researchers will select the articles and extract the data independently. The conceptual model proposed by Castro and Canella will guide the data extraction and analysis. The results will be presented with narrative synthesis for the extracted data accompanying the tabulated and charted results.Ethics and disseminationThis study is based on the analysis of published scientific literature and did not involve patients, medical research, or any type of personal information; therefore, no ethical approval was obtained for this study. The results of this scoping review will be submitted for publication in an international peer-reviewed journal, preferably open access.
Which aspects of patient experience are the ‘moment of truth’ in the healthcare context: a multicentre cross-sectional study in China
Authors: Chen Xiao , Yuan Jie , Zhao Wenjuan , Qin Wei , Gao Jian , Zhang Yuxia 
Published: February 2024

ObjectiveThis study aimed to examine the differential magnitude of associations between specific dimensions of patient experience and overall patient satisfaction.DesignA descriptive, cross-sectional design was used to collect patient experience and overall satisfaction data.SettingParticipants were recruited at one tertiary general hospital, one tertiary specialised hospital, and one secondary hospital in Shanghai, China. These three institutes represent the main kinds of hospitals in the Chinese healthcare system.Participants1532 inpatients were recruited, and 1469 were included. The inclusion criteria were as follows: (1) having received inpatient service for at least 2 days; (2) able to understand the questions in the questionnaires; and (3) aged>18 years old. Patients who had impaired cognitive function and completed the questionnaires with missing information were excluded.Primary and secondary outcome measurePatient experience was measured using the Inpatient Experience with Nursing Care Scale, which is widely used in the China. The overall patient satisfaction was measured with 10-point response option.ResultsThe LASSO (least absolute shrinkage and selection operator) regression results showed that as the penalty factor (λ) = 0.0162, age, marriage status, financial status, length of hospital stay and numbers of previous of hospitalisation and six dimensions of nursing care remained in the model. As λ increases to 0.1862, only four patient experience variables, potentially the most influential on patient satisfaction, remained in the model. Patient experience with emotional support was the most significant dimension explaining patient satisfaction (β=0.1564), the second most significant dimension was admission and discharge management (β=0.1562), and the third was monitoring and coping with the progress of diseases (β=0.0613).ConclusionPatient experience with emotional support, admission and discharge management, monitoring and coping with the progress of diseases, and information and education are the most significant dimensions explaining patient satisfaction.
Assessing the heterogeneity of the impact of COVID-19 incidence on all-cause excess mortality among healthcare districts in Lombardy, Italy, to evaluate the local response to the pandemic: an ecological study
Authors: Paganuzzi Marco , Nattino Giovanni , Ghilardi Giulia Irene , Costantino Giorgio , Rossi Carlotta , Cortellaro Francesca , Cosentini Roberto , Paglia Stefano , Migliori Maurizio , Mira Antonietta , Bertolini Guido 
Published: February 2024

ObjectivesThe fragmentation of the response to the COVID-19 pandemic at national, regional and local levels is a possible source of variability in the impact of the pandemic on society. This study aims to assess how much of this variability affected the burden of COVID-19, measured in terms of all-cause 2020 excess mortality.DesignEcological retrospective study.SettingLombardy region of Italy, 2015–2020.Outcome measuresWe evaluated the relationship between the intensity of the epidemics and excess mortality, assessing the heterogeneity of this relationship across the 91 districts after adjusting for relevant confounders.ResultsThe epidemic intensity was quantified as the COVID-19 hospitalisations per 1000 inhabitants. Five confounders were identified through a directed acyclic graph: age distribution, population density, pro-capita gross domestic product, restriction policy and population mobility.Analyses were based on a negative binomial regression model with district-specific random effects. We found a strong, positive association between COVID-19 hospitalisations and 2020 excess mortality (p<0.001), estimating that an increase of one hospitalised COVID-19 patient per 1000 inhabitants resulted in a 15.5% increase in excess mortality. After adjusting for confounders, no district differed in terms of COVID-19-unrelated excess mortality from the average district. Minimal heterogeneity emerged in the district-specific relationships between COVID-19 hospitalisations and excess mortality (6 confidence intervals out of 91 did not cover the null value).ConclusionsThe homogeneous effect of the COVID-19 spread on the excess mortality in the Lombardy districts suggests that, despite the unprecedented conditions, the pandemic reactions did not result in health disparities in the region.
‘That gave me a lot of comfort, that he would ask my opinion about how we wanted to talk about this’: A qualitative analysis of clinical communication experiences of ostomy patients
Authors: Lazenby Braidyn S , Guidry Ashley , Donovan Erin E , Dailey René , Ivatury Srinivas Joga 
Published: February 2024

ObjectivesThe purpose of this study was to investigate the communication challenges and successes that people with ostomies experienced during their healthcare encounters.DesignWe conducted semistructured interviews of people with ostomies. Interviews focused on important social situations and health communication strategies for managing these situations. We transcribed interviews and coded them to create themes.ParticipantsParticipants were eligible to participate if they were above the age of 18 and have had an ostomy for at least a year. 27 people participated in the study.SettingThe study was conducted in a university setting.ResultsInterviews with ostomates surfaced several themes related to ostomate needs. Participants benefited from communication that was open, thorough and had a positive outlook on ostomies. Participants found patient–clinician communication to be challenging when there was a lack of knowledge surrounding ostomy care, communication was unclear or inadequate, and when clinicians had a negative outlook on ostomies.ConclusionsFindings from this project are intended to amplify existing patient and clinician education materials and to inform the creation of a communication guide specifically for the ostomy context.
Sustained benefits of a generalist training programme for UK doctors: a survey-based follow-up study
Authors: Cserző Dorottya , Bullock Alison 
Published: February 2024

ObjectivesThe study aimed to conduct a follow-up of all broad-based training (BBT) trainees who participated in the original evaluation completed in 2017. The follow-up study explored the impact of BBT on career decisions, sustained benefits and unintended disadvantages of the programme, and views on the future of training.DesignScoping interviews informed the design of an online survey. The interview transcripts were analysed thematically. The survey was piloted with six volunteers and sent out to all former BBT trainees. Data from the survey were transferred to Excel and SPSS for analysis. The open-text comments on the survey were subject to a thematic content analysis.SettingParticipants were working in general practice, paediatrics, psychiatry or medicine.ParticipantsEight former BBT trainees participated in the scoping interviews. Interview participants were selected to ensure a diversity of current specialties and to represent all three BBT cohorts. All former BBT trainees were invited to complete the survey (n=118) and 70 replied.ResultsThe benefits of BBT were sustained over time: participants were confident in their career decisions, took a holistic approach to care and capitalised on their experiences in other specialties in their current roles. A minority of trainees also experienced temporary challenges when they joined a specialty training programme after completing the BBT. Whatever their specialty, experience in core medicine, paediatrics, psychiatry and general practice was valued. Disadvantages were short-lived (catching up on transition specialty training) or affected a minority (impact on sense of belonging).ConclusionsThe BBT programme supported the development of generalist doctors. Greater attention needs to be given to training secondary care doctors who take a holistic view of the patient and navigate their specialist care.
Lower airway microbiota in COPD and healthy controls
Authors: Tangedal Solveig , Nielsen Rune , Aanerud Marianne , Drengenes Christine , Husebø Gunnar R , Lehmann Sverre , Knudsen Kristel S , Hiemstra Pieter S , Eagan Tomas ML 
Published: February 2024

BackgroundThe lower airway microbiota in patients with chronic obstructive pulmonary disease (COPD) are likely altered compared with the microbiota in healthy individuals. Information on how the microbiota is affected by smoking, use of inhaled corticosteroids (ICS) and COPD severity is still scarce.MethodsIn the MicroCOPD Study, participant characteristics were obtained through standardised questionnaires and clinical measurements at a single centre from 2012 to 2015. Protected bronchoalveolar lavage samples from 97 patients with COPD and 97 controls were paired-end sequenced with the Illumina MiSeq System. Data were analysed in QIIME 2 and R.ResultsAlpha-diversity was lower in patients with COPD than controls (Pielou evenness: COPD=0.76, control=0.80, p=0.004; Shannon entropy: COPD=3.98, control=4.34, p=0.01). Beta-diversity differed with smoking only in the COPD cohort (weighted UniFrac: permutational analysis of variance R2=0.04, p=0.03). Nine genera were differentially abundant between COPD and controls. Genera enriched in COPD belonged to theFirmicutesphylum. Pack years were linked to differential abundance of taxa in controls only (ANCOM-BC (Analysis of Compositions of Microbiomes with Bias Correction) log-fold difference/q-values:Haemophilus−0.05/0.048;Lachnoanaerobaculum−0.04/0.03).Oribacteriumwas absent in smoking patients with COPD compared with non-smoking patients (ANCOM-BC log-fold difference/q-values: −1.46/0.03). We found no associations between the microbiota and COPD severity or ICS.ConclusionThe lower airway microbiota is equal in richness in patients with COPD to controls, but less even. Genera from theFirmicutesphylum thrive particularly in COPD airways. Smoking has different effects on diversity and taxonomic abundance in patients with COPD compared with controls. COPD severity and ICS use were not linked to the lower airway microbiota.
Targeting TACC3 Induces Immunogenic Cell Death and Enhances T-DM1 Response in HER2-Positive Breast Cancer
Authors: Gedik Mustafa Emre , Saatci Ozge , Oberholtzer Nathaniel , Uner Meral , Akbulut Caliskan Ozge , Cetin Metin , Aras Mertkaya , Ibis Kubra , Caliskan Burcu , Banoglu Erden , Wiemann Stefan , Üner Ayşegül , Aksoy Sercan , Mehrotra Shikhar , Sahin Ozgur 
Published: February 2024

Abstract

Trastuzumab emtansine (T-DM1) was the first and one of the most successful antibody–drug conjugates (ADC) approved for treating refractory HER2-positive breast cancer. Despite its initial clinical efficacy, resistance is unfortunately common, necessitating approaches to improve response. Here, we found that in sensitive cells, T-DM1 induced spindle assembly checkpoint (SAC)-dependent immunogenic cell death (ICD), an immune-priming form of cell death. The payload of T-DM1 mediated ICD by inducing eIF2α phosphorylation, surface exposure of calreticulin, ATP and HMGB1 release, and secretion of ICD-related cytokines, all of which were lost in resistance. Accordingly, ICD-related gene signatures in pretreatment samples correlated with clinical response to T-DM1–containing therapy, and increased infiltration of antitumor CD8+ T cells in posttreatment samples was correlated with better T-DM1 response. Transforming acidic coiled-coil containing 3 (TACC3) was overexpressed in T-DM1–resistant cells, and T-DM1 responsive patients had reduced TACC3 protein expression whereas nonresponders exhibited increased TACC3 expression during T-DM1 treatment. Notably, genetic or pharmacologic inhibition of TACC3 restored T-DM1–induced SAC activation and induction of ICD markers in vitro. Finally, TACC3 inhibition in vivo elicited ICD in a vaccination assay and potentiated the antitumor efficacy of T-DM1 by inducing dendritic cell maturation and enhancing intratumoral infiltration of cytotoxic T cells. Together, these results illustrate that ICD is a key mechanism of action of T-DM1 that is lost in resistance and that targeting TACC3 can restore T-DM1–mediated ICD and overcome resistance.

Significance:
Loss of induction of immunogenic cell death in response to T-DM1 leads to resistance that can be overcome by targeting TACC3, providing an attractive strategy to improve the efficacy of T-DM1.