bluuebunny/crossref_metadata_2025 huggingface dataset:
Astronomers explain ‘baffling’ James Webb Space Telescope image of binary star
Authors: Banks Michael
Published: January 2023

Astronomers have explained that concentric geometric ripples around distant binary star WR140 are a series of huge dust shells created by the cyclic interaction between a pair of hot stars locked together in a tight orbit.
Entangled winners
Authors: Durrani Matin
Published: January 2023

Mysteries of entanglement lies at the heart of this year’s Nobel Prize for Physics.
Reforming how we evaluate students
Authors: Labrosse Nicolas
Published: January 2023

Nicolas Labrosse says we must change how universities evaluate physics students.
Life after the leak
Authors: Crease Robert P
Published: January 2023

Why did a tiny leak bring down a hugely successful research reactor 25 years ago? Robert P Crease reveals the lessons we can learn.
Costly particle physics
Authors: Goodman Maurice
Published: January 2023

A response to the news story about a study claiming that the proposed Future Circular Collider (FCC) is the greenest of various planned “Higgs factories”.
Lovely in Liverpool
Authors: Qaim Syed
Published: January 2023

A response to a feature by Rob Lea, which examined the lost history of the University of Liverpool’s synchrocyclotron.
Ask me anything: Janina Moereke
Authors: Durrani Matin
Published: January 2023

Janina Moereke is a development engineer at Avancis in Munich, Germany, where she uses optical and electrical techniques to characterise and develop thin-film solar cells.
Feasibility and performance analysis of bifacial module under extremely hot and dry climate
Authors: Verma Deepak , Shah Jainam , Patel Nisarg , Patel Rushil , Patel Dhruvil
Published: January 2023

Solar panels with a bi-facial design provide energy from both sides; thus, it would be interesting to examine the viability of such modules in an extremely hot and dry city like Ahmedabad, Gujarat, India. This study assesses the temperature, efficiency, and bifacial gain of PV bifacial modules as a function of solar irradiation, ambient temperature, wind speed, and additional parameters. The global horizontal irradiance has been used in this study to calculate Direct Normal Irradiance (DNI), Diffuse Horizontal Irradiance (DHI) and Front and Rear Irradiance. The results show that an optimal tilt angle of 43.5° provides the best efficiency of 24% at ambient temperature. For a constant value of tilt angle, the bi-facial gain of the module increases linearly with albedo factor. It has also been discovered that continuing to raise the elevation beyond 1 meter will eventually diminish the bifacial gain because the reflected and diffuse irradiance will become less intense on the rear side of the bifacial module.
Effectiveness of outpatient geriatric rehabilitation after inpatient geriatric rehabilitation or hospitalisation: a systematic review and meta-analysis
Authors: Preitschopf Astrid , Holstege Marije , Ligthart Andrea , Groen Wim , Burchell George , Pol Margriet , Buurman Bianca
Published: January 2023

Background

Due to the increasing number of older people with multi-morbidity, the demand for outpatient geriatric rehabilitation (OGR) will also increase.

Objective

To assess the effects of OGR on the primary outcome functional performance (FP) and secondary outcomes: length of in-patient stay, re-admission rate, patients’ and caregivers’ quality of life, mortality and cost-effectiveness. We also aim to describe the organisation and content of OGR.

Methods

Systematic review and meta-analysis. Five databases were queried from inception to July 2022. We selected randomised controlled trials written in English, focusing on multidisciplinary interventions related to OGR, included participants aged ≥65 and reported one of the main outcomes. A meta-analysis was performed on FP, patients’ quality of life, length of stay and re-admissions. The structural, procedural and environmental aspects of OGR were systematically mapped.

Results

We selected 24 studies involving 3,405 participants. The meta-analysis showed no significant effect on the primary outcome FP (activity). It demonstrated a significant effect of OGR on shortening length of in-patient stay (P = 0.03, MD = −2.41 days, 95%CI: [−4.61—0.22]). Frequently used elements of OGR are: inpatient start of OGR with an interdisciplinary rehabilitation team, close cooperation with primary care, an OGR coordinator, individual goal setting and education for both patient and caregiver.

Conclusion

This review showed that OGR is as effective as usual care on FP activity. It shows low certainty of evidence for OGR being effective in reducing the length of inpatient stay. Further research is needed on the various frequently used elements of OGR.
The frailty index based on laboratory test data as a tool to investigate the impact of frailty on health outcomes: a systematic review and meta-analysis
Authors: Sapp David G , Cormier Brianna M , Rockwood Kenneth , Howlett Susan E , Heinze Stefan S
Published: January 2023

The frailty index (FI) quantifies frailty as deficit accumulation. It has been adapted to employ laboratory test data (FI-Lab). Our objective was to systematically review and meta-analyse the FI-Lab’s ability to predict mortality. Secondary objectives were to review the FI-Lab’s association with adverse health outcomes and whether FI-Lab scores differed between the sexes. A systematic literature search was carried out using six online databases to identify studies that measured the FI-Lab in humans. Hazard ratios (HRs) were combined in a meta-analysis to create a pooled risk estimate for mortality. Of the 1,201 papers identified, spanning January 2010 until 11 July 2022, 38 were included. FI-Lab scores per 0.01 unit increase predicted mortality overall (HR = 1.04; 95% confidence interval (CI) = 1.03–1.05) and for studies with a mean age of 81+ years (HR = 1.04; 95% CI = 1.03–1.05). The quality of evidence for these meta-analyses are moderate and high, respectively. Further, higher FI-Lab scores were associated with more frequent adverse health outcomes. Sex differences in FI-Lab scores varied, with no consistent indication of a sex effect. The FI-Lab is associated with mortality and with a variety of adverse health outcomes. No consistent sex differences in FI-Lab scores were observed, with several studies in disagreement. Notably, these conclusions were most relevant to older (65+ years old) individuals; further evidence in younger people is needed in both clinical and population representative studies.
Dealing with requests for euthanasia in incompetent patients with dementia. Qualitative research revealing underexposed aspects of the societal debate
Authors: Coers Djura O , de Boer Marike E , Sizoo Eefje M , Smalbrugge Martin , Leget Carlo J W , Hertogh Cees M P M
Published: January 2023

Objectives

In the Netherlands, a case of euthanasia of an incompetent patient with dementia and an advance euthanasia directive (AED) caused great societal unrest and led to a petition signed by more than 450 physicians. In this paper, we investigate these physicians’ reasons and underlying motives for supporting the ‘no sneaky euthanasia’ petition, with the aim of gaining insight into the dilemmas experienced and to map out topics in need of further guidance.

Methods

Twelve in-depth interviews were conducted with physicians recruited via the webpage ‘no sneaky euthanasia’. General topics discussed were: reasons for signing the petition, the possibilities of euthanasia in incompetent patients and views on good end-of-life care. Data were interpreted using thematic content analysis and the framework method.

Results

Reasons for supporting the petition are dilemmas concerning ‘sneaky euthanasia’, the over-simplified societal debate, physicians’ personal moral boundaries and the growing pressure on physicians. Analysis revealed three underlying motives: aspects of handling a euthanasia request based on an AED, good end-of-life care and the doctor as a human being.

Conclusions

Although one of the main reasons for participants to support the petition was the opposition to ‘sneaky euthanasia’, our results show a broader scope of reasons. This includes their experience of growing pressure to comply with AEDs, forcing them to cross personal boundaries. The underlying motives are related to moral dilemmas around patient autonomy emerging in cases of decision-making disabilities in advanced dementia. To avoid uncertainty regarding patients’ wishes, physicians express their need for reciprocal communication.
Weight loss, visit-to-visit body weight variability and cognitive function in older individuals
Authors: Zonneveld Michelle H , Noordam Raymond , Sabayan Behnam , Stott David J , Mooijaart Simon P , Blauw Gerard J , Jukema J Wouter , Sattar Naveed , Trompet Stella
Published: January 2023

Objective

to investigate the association between variability and loss of body weight with subsequent cognitive performance and activities of daily living in older individuals.

Design

cross-sectional cohort study.

Setting

PROspective Study of Pravastatin in the Elderly at Risk, multicentre trial with participants from Scotland, Ireland and the Netherlands.

Subjects

4,309 participants without severe cognitive dysfunction (mean age 75.1 years, standard deviation (SD) = 3.3), at higher risk for cardiovascular disease (CVD).

Methods

body weight was measured every 3 months for 2.5 years. Weight loss was defined as an average slope across all weight measurements and as ≥5% decrease in baseline body weight during follow-up. Visit-to-visit variability was defined as the SD of weight measurements (kg) between visits. Four tests of cognitive function were examined: Stroop test, letter-digit coding test (LDCT), immediate and delayed picture-word learning tests. Two measures of daily living activities: Barthel Index (BI) and instrumental activities of daily living (IADL). All tests were examined at month 30.

Results

both larger body weight variability and loss of ≥5% of baseline weight were independently associated with worse scores on all cognitive tests, but minimally with BI and IADL. Compared with participants with stable weight, participants with significant weight loss performed 5.83 seconds (95% CI 3.74; 7.92) slower on the Stroop test, coded 1.72 digits less (95% CI −2.21; −1.13) on the LDCT and remembered 0.71 pictures less (95% CI -0.93; −0.48) on the delayed picture-word learning test.

Conclusion

in older people at higher risk for CVD, weight loss and variability are independent risk-factors for worse cognitive function.
Invited Commentary: On the Mathematization of Epidemiology as a Socially Engaged Quantitative Science
Authors: Cartus Abigail R , Marshall Brandon D L
Published: January 2023

Ensuring that patients with opioid use disorder (OUD) have access to optimal medication therapies is a critical challenge in substance use epidemiology. Rudolph et al. (Am J Epidemiol. 2023;XXX(X):XXXX-XXXX) demonstrated that sophisticated data-adaptive statistical techniques can be used to learn optimal, individualized treatment rules that can aid providers in choosing a medication treatment modality for a particular patient with OUD. This important work also highlights the effects of the mathematization of epidemiologic research. Here, we define mathematization and demonstrate how it operates in the context of effectiveness research on medications for OUD using the paper by Rudolph et al. as a springboard. In particular, we address the normative dimension of mathematization and how it tends to resolve a fundamental tension in epidemiologic practice between technical sophistication and public health considerations in favor of more technical solutions. The process of mathematization is a fundamental part of epidemiology; we argue not for eliminating it but for balancing mathematization and technical demands equally with practical and community-centric public health needs.
Emulating a Target Trial Using Primary-Care Electronic Health Records: Sodium-Glucose Cotransporter 2 Inhibitor Medications and Hemoglobin A1c
Authors: Kalia Sumeet , Saarela Olli , O’Neill Braden , Meaney Christopher , Moineddin Rahim , Sullivan Frank , Greiver Michelle
Published: January 2023

Substantial effort has been dedicated to conducting randomized controlled experiments to generate clinical evidence for diabetes treatment. Randomized controlled experiments are the gold standard for establishing cause and effect. However, due to their high cost and time commitment, large observational databases such as those comprised of electronic health record (EHR) data collected in routine primary care may provide an alternative source with which to address such causal objectives. We used a Canadian primary-care data repository housed at the University of Toronto (Toronto, Ontario, Canada) to emulate a randomized experiment. We estimated the effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT-2i) medications for patients with diabetes using hemoglobin A1c (HbA1c) as a primary outcome and marker for glycemic control from 2018 to 2021. We assumed an intention-to-treat analysis for prescribed treatment, with analyses based on the treatment assigned rather than the treatment eventually received. We defined the causal contrast of interest as the net change in HbA1c (percent) between the group receiving the standard of care versus the group receiving SGLT-2i medication. Using a counterfactual framework, marginal structural models demonstrated a reduction in mean HbA1c level with the initiation of SGLT-2i medications. These findings provided effect sizes similar to those from earlier clinical trials on assessing the effectiveness of SGLT-2i medications.
Validation of Fespixon in Postoperative Scar Cosmesis Using Quantitative Digital Photography Analysis
Authors: Huang Tien-Ru , Chen Shyi-Gen , Chen Jui-Ching , Liu Shao-Cheng
Published: January 2023

Background

Unsightly scarring after surgery remains a dilemma. One of the challenges is the lack of objective scar assessment tools.

Objectives

This study aimed to evaluate the efficacy of a novel medicine, Fespixon, for prevention and/or alleviation of post–skin incision scarring. A second aim was to demonstrate the practicality of our digital image analysis system to see if this could serve as a sensitive tool to assess scar improvement.

Methods

A prospective, placebo-controlled trial involving patients with postoperative transverse scars was conducted. Each patient received a topical formulation of Fespixon on the left part of the scar and placebo cream on the right. In addition to recording the subjective modified Vancouver Scar Scale and visual analog scale scores, we utilized digital photography for monthly scar analysis, with CIELAB and hue serving as the colorimetric information, and with contrast, correlation, homogeneity, and entropy providing texture information.

Results

Forty-six participants (mean age, 52 years) were enrolled in the trial. All the parameters of subjective assessment showed superior results for the Fespixon-treated side, with significant differences in pigmentation, vascularity, pliability, height, itchiness, and patient satisfaction (P = .043, .013, .026, .002, .039, .012, respectively). The trends in color and texture showed increased relative difference ratios, with significant differences in most of the eigenvalues towards the Fespixon-treated side, including CIELAB-L* (P < 0.001), hue-R,G,B (red, blue, green) values (P = .034, .001, .011), contrast (P < 0.001), homogeneity (P < 0.001), correlation (P = .011), and entropy (P < 0.001).

Conclusions

We validated the efficacy of Fespixon for postoperative scar healing based not only on subjective assessments but also on objective quantitative analyses. The results also indicated that our digital photography quantitative analysis system is an ideal tool for quantification of scar appearance.

Level of Evidence: 3
Pollen characteristics used in determination and systematics of Quercus (Fagaceae): new data and verification of previous concepts
Authors: Tekleva Maria V , Polevova Svetlana , Naryshkina Natalia N
Published: January 2023

Quercus (oaks) is a large and important genus of woody angiosperms occurring in a wide range of environments and often occupying a dominant position in temperate forests of the Northern Hemisphere or being a minor component in some subtropical and tropical forests. A reliable determination of fossil dispersed oak pollen requires combined light, scanning electron (SEM) and transmission electron microscopy (TEM) studies and relevant comparative data on extant oak species. We provide SEM and TEM data on 22 extant Quercus spp., representing all sections of the genus. The main objectives of our study were to clarify the nature of the so-called geniculus, a characteristic equatorial bulge in the exine of the colpus found in many oak species, and to test previous hypotheses about the structural basic units of the exine in Quercus. Our ontogenetic study and oxidative experiment involving several Quercus spp. and one Trigonobalanus sp. resulted in a more accurate interpretation of the nature of the geniculus and exine elements, their different developmental states and, therefore, their more reliable application in the systematics and evolution of the genus Quercus and Fagaceae in general.
Grasping the opportunity: better behavioural diagnoses will lead to better treatments for stroke
Authors: Ward Nick
Published: January 2023

Hensel et al. combine fMRI, rTMS and 3D hand movement analyses to test the contributions of contralesional motor cortex (M1) and anterior parietal sulcus (aIPS) to motor recovery post-stroke. The results reveal differential roles of M1 and aIPS in different aspects of recovered hand motor function, depending on interhemispheric connectivity.

This scientific commentary refers to ‘Recovered grasping performance after stroke depends on interhemispheric frontoparietal connectivity’ by Hensel et al. (https://doi.org/10.1093/brain/awac157).
Genetic variation in the human olfactory receptor OR5AN1 associates with the perception of musks
Authors: Sato-Akuhara Narumi , Trimmer Casey , Keller Andreas , Niimura Yoshihito , Shirasu Mika , Mainland Joel D , Touhara Kazushige
Published: January 2023

Humans have significant individual variations in odor perception, derived from their experience or sometimes from differences in the olfactory receptor (OR) gene repertoire. In several cases, the genetic variation of a single OR affects the perception of its cognate odor ligand. Musks are widely used for fragrance and are known to demonstrate specific anosmia. It, however, remains to be elucidated whether the OR polymorphism contributes to individual variations in musk odor perception. Previous studies reported that responses of the human musk receptor OR5AN1 to a variety of musks in vitro correlated well with perceptual sensitivity to those odors in humans and that the mouse ortholog, Olfr1440 (MOR215-1), plays a critical role in muscone perception. Here, we took advantage of genetic variation in OR5AN1 to examine how changes in receptor sensitivity are associated with human musk perception. We investigated the functional differences between OR5AN1 variants in an in vitro assay and measured both perceived intensity and detection threshold in human subjects with different OR5AN1 genotypes. Human subjects homozygous for the more sensitive L289F allele had a lower detection threshold for muscone and found macrocyclic musks to be more intense than subjects homozygous for the reference allele. These results demonstrate that the genetic variation in OR5AN1 contributes to perceptual differences for some musks. In addition, we found that the more functional variant of OR5A1, a receptor involved in β-ionone perception, is associated with the less functional variant of OR5AN1, suggesting that the perceived intensities of macrocyclic musks and β-ionone are inversely correlated.
Asymptomatic hyperuricaemia in chronic kidney disease: mechanisms and clinical implications
Authors: Anders Hans-Joachim , Li Qiubo , Steiger Stefanie
Published: January 2023

Asymptomatic hyperuricaemia (HU) is considered a pathogenic factor in multiple disease contexts, but a causative role is only proven for the crystalline form of uric acid in gouty arthritis and urate nephropathy. Epidemiological studies document a robust association of HU with hypertension, cardiovascular disease (CVD) and CKD progression, but CKD-related impaired uric acid (UA) clearance and the use of diuretics that further impair UA clearance likely accounts for these associations. Interpreting the available trial evidence is further complicated by referring to xanthine oxidase inhibitors as urate-lowering treatment, although these drugs inhibit other substrates, so attributing their effects only to HU is problematic. In this review we provide new mechanistic insights into the biological effects of soluble and crystalline UA and discuss clinical evidence on the role of asymptomatic HU in CKD, CVD and sterile inflammation. We identify research areas with gaps in experimental and clinical evidence, specifically on infectious complications that represent the second common cause of death in CKD patients, referred to as secondary immunodeficiency related to kidney disease. In addition, we address potential therapeutic approaches on how and when to treat asymptomatic HU in patients with kidney disease and where further interventional studies are required.
ECCO Topical Review on Biological Treatment Cycles in Crohn’s Disease
Authors: Noor Nurulamin M , Sousa Paula , Bettenworth Dominik , Gomollón Fernando , Lobaton Triana , Bossuyt Peter , Casanova Maria Jose , Ding Nik S , Dragoni Gabriele , Furfaro Federica , van Rheenen Patrick F , Chaparro Maria , Gisbert Javier P , Louis Edouard , Papamichail Konstantinos
Published: January 2023

There are now a growing number of licensed biological therapies for patients with Crohn’s disease. However, there can be significant costs associated with long-term maintenance treatment, as well as some concerns about potential side-effects. As a result, there has been increasing interest in elective biological treatment discontinuation in selected patients, after a sustained period of remission. Following discontinuation, in cases of relapse, evidence to date has suggested that remission may often be regained by re-treatment with the same biological agent. Therefore, a concept has emerged in which cycles of biological therapy might be used. If this treatment strategy were to be applied in a subgroup of patients at low risk of relapse, cycling might allow a substantial number of patients to have a lower, overall therapeutic burden—ensuring decreased exposure to biological therapy but still enabling appropriate disease control.

Currently, there remains uncertainty about the benefit–risk balance for using cycles of biological treatment for patients with Crohn’s disease. Accordingly, an expert panel was convened by the European Crohn’s and Colitis Organisation [ECCO] to review the published literature and agree a series of consensus practice points. The panel aimed to provide evidence-based guidance on multiple aspects of biological treatment discontinuation and cycling, including the risk of relapse after elective treatment discontinuation, predictors of probable relapse or remission, safety, patient preferences, and pharmacoeconomic aspects. Crucially, discussions about biological treatment discontinuation and cycling should be individualized, to enable shared decision-making by patients with their clinicians.
Ready or not, here I come: the significance of information about educational success for educational decisions
Authors: Larsen Kira Solveig
Published: January 2023

This study analyses the effect of the Educational Readiness Assessment (ERA)—a scheme that categorizes students in Denmark as either ‘ready’ or ‘not ready’ for upper secondary education—on educational decision-making. Because the ERA uses a grade-specific cut-off to determine readiness, it can be used in a fuzzy regression discontinuity design to estimate the causal effect of the ERA on educational decision-making. Inspired by the theory of Relative Risk Aversion (RRA), the study argues that non-service-class students respond to a negative signal by postponing the decision (not) to continue to upper secondary education, while service-class students proceed regardless of receiving a negative signal. Empirical results are mostly consistent with RRA. The policy implications of the results are that students do respond to information regarding the likelihood of educational success, but respond differently depending on their social class position.
Mixotrophy broadens the ecological niche range of the iron oxidizerSideroxydanssp. CL21 isolated from an iron-rich peatland
Authors: Cooper Rebecca E , Finck Jessica , Chan Clara , Küsel Kirsten
Published: January 2023

Sideroxydans sp. CL21 is a microaerobic, acid-tolerant Fe(II)-oxidizer, isolated from the Schlöppnerbrunnen fen. Since the genome size of Sideroxydans sp. CL21 is 21% larger than that of the neutrophilic Sideroxydans lithotrophicus ES-1, we hypothesized that strain CL21 contains additional metabolic traits to thrive in the fen. The common genomic content of both strains contains homologs of the putative Fe(II) oxidation genes, mtoAB and cyc2. A large part of the accessory genome in strain CL21 contains genes linked to utilization of alternative electron donors, including NiFe uptake hydrogenases, and genes encoding lactate uptake and utilization proteins, motility and biofilm formation, transposable elements, and pH homeostasis mechanisms. Next, we incubated the strain in different combinations of electron donors and characterized the fen microbial communities. Sideroxydans spp. comprised 3.33% and 3.94% of the total relative abundance in the peatland soil and peatland water, respectively. Incubation results indicate Sideroxydans sp. CL21 uses H2 and thiosulfate, while lactate only enhances growth when combined with Fe, H2, or thiosulfate. Rates of H2 utilization were highest in combination with other substrates. Thus, Sideroxydans sp. CL21 is a mixotroph, growing best by simultaneously using substrate combinations, which helps to thrive in dynamic and complex habitats.
Socioeconomic and Contextual Differentials in Memory Decline: A Cross-Country Investigation Between England and China
Authors: Cadar Dorina , Brocklebank Laura , Yan Li , Zhao Yaohui , Steptoe Andrew
Published: January 2023

Objectives

Although cognitive functioning is strongly associated with biological changes in the brain during the aging process, very little is known about the role of sociocultural differentials between the western and eastern parts of the world. We examined the associations between individual socioeconomic markers (e.g., education, household wealth) and contextual levels characteristics (e.g., urbanicity) with memory performance and memory decline over up to 8 years of follow-up in England and China.

Methods

The analytical samples included participants aged 50+ from the English Longitudinal Study of Aging (n = 6,687) and the China Health and Retirement Longitudinal Study (n = 10,252). Mixed linear models were employed to examine the association between baseline individual socioeconomic markers (education, wealth) and contextual-level characteristics (urbanicity) on the change in memory over time.

Results

Our analyses showed that higher education and wealth were associated with better baseline memory in both England and China. Still, the impact of contextual-level characteristics such as urbanicity differed between the 2 countries. For English individuals, living in a rural area showed an advantage in memory, while the opposite pattern was observed in China. Memory decline appeared to be socioeconomically patterned by higher education, wealth, and urbanicity in China but not in England.

Discussion

Our findings highlight substantial socioeconomic and contextual inequity in memory performance in both England and China, as well as in the rate of memory decline primarily in China. Public health strategies for preventing memory decline should target the socioeconomic gaps at the individual and contextual levels to protect those particularly disadvantaged.
Examining Satisfaction and Quality in Home- and Community-Based Service Programs in the United States: A Scoping Review
Authors: Bucy Taylor I , Mulcahy John F , Shippee Tetyana P , Fashaw-Walters Shekinah , Dahal Roshani , Duan Yinfei , Jutkowitz Eric
Published: January 2023

Background and Objectives

Long-term services and supports in the United States are increasingly reliant on home- and community-based services (HCBS). Yet, little is known about the quality of HCBS. We conducted a scoping review of the peer-reviewed literature to summarize HCBS consumer, provider, and stakeholder satisfaction with services as a means of assessing quality.

Research Design and Methods

We searched PubMed, OVID-MEDLINE, and SCOPUS to identify articles published from 2000 to 2021 that reported on studies describing a U.S.-based study population. Articles were grouped into 3 categories: drivers of positive consumer satisfaction, drivers of negative consumer satisfaction, and provider and stakeholder perspectives on satisfaction.

Results

Our final sample included 27 articles. Positive perceptions of quality and reported satisfaction with services were driven by consistent, reliable, and respectful care providers, and adoption of person-centered models of service delivery. Mistreatment of consumers, staff turnover, training, service interruptions, and unmet functional needs were drivers of negative consumer perceptions of quality. Support for caregivers and emphasis on training were identified by providers and stakeholders as important for providing satisfactory services.

Discussion and Implications

Multiple data challenges limit the ability to systematically evaluate HCBS program quality; however, studies examining single programs found that HCBS consumers are more satisfied and associate higher quality with easy-to-navigate programs and professional staff. Efforts to expand HCBS should also include requirements to systematically evaluate quality outcomes.
Students as teachers: effect of the peer education model on reducing smartphone addiction in adolescents
Authors: Avci Dilek , Gündoğdu Nurcan Akgül , Dönmez Recep Hakan , Avci Fikret Eren
Published: January 2023

The group at the highest risk of smartphone addiction is adolescents. In particular during the coronavirus disease 2019 pandemic, factors such as conducting education online, curfew and the increase in the monotonous time spent at home have led to an increase in the use of smartphones among adolescents. Therefore, this study aimed to determine the effect of the peer education model on reducing smartphone addiction in adolescents. The present semi-experimental study with a pre-test–post-test control group was carried out with 622 high school students in Turkey. The study was carried out between September 2021 and February 2022 in two stages. In the first stage, the peer educator education program on smartphone addiction in adolescents was implemented. In the second stage, the peer education program was implemented and monitored. While there was no significant difference between the intervention and control groups in terms of the mean scores they obtained from the Smartphone Addiction Scale at the pre-test (P > 0.05), the difference between them was statistically significant at the post-test (P < 0.001). This study demonstrated that the peer education model was effective in reducing smartphone addiction in adolescents. Thus, it can be recommended that school-based peer education programs for adolescents should be prepared and implemented.
No effect of ocean acidification on growth, photosynthesis, or dissolved organic carbon release by three temperate seaweeds with different dissolved inorganic carbon uptake strategies
Authors: Paine Ellie R , Britton Damon , Schmid Matthias , Brewer Elizabeth A , Diaz-Pulido Guillermo , Boyd Philip W , Hurd Catriona L
Published: January 2023

In a future ocean, dissolved organic carbon (DOC) release by seaweed has been considered a pathway for organic carbon that is not incorporated into growth under carbon dioxide (CO2) enrichment/ocean acidification (OA). To understand the influence of OA on seaweed DOC release, a 21-day experiment compared the physiological responses of three seaweed species, two which operate CO2 concentrating mechanisms (CCMs), Ecklonia radiata (C. Agardh) J. Agardh and Lenormandia marginata (Hooker F. and Harvey) and one that only uses CO2 (non-CCM), Plocamium cirrhosum (Turner) M.J. Wynne. These two groups (CCM and non-CCM) are predicted to respond differently to OA dependent on their affinities for Ci (defined as CO2 + bicarbonate, HCO3−). Future ocean CO2 treatment did not drive changes to seaweed physiology—growth, Ci uptake, DOC production, photosynthesis, respiration, pigments, % tissue carbon, nitrogen, and C:N ratios—for any species, regardless of Ci uptake method. Our results further showed that Ci uptake method did not influence DOC release rates under OA. Our results show no benefit of elevated CO2 concentrations on the physiologies of the three species under OA and suggest that in a future ocean, photosynthetic CO2 fixation rates of these seaweeds will not increase with Ci concentration.
Quantitative bias analysis of prevalence under misclassification: evaluation indicators, calculation method and case analysis
Authors: Liu Jin , Wang Shiyuan , Shao Fang
Published: January 2023

Prevalence estimates are fundamental to epidemiological studies. Although they are highly vulnerable to misclassification bias, the risk of bias assessment of prevalence estimates is often neglected. Quantitative bias analysis (QBA) can effectively estimate misclassification bias in epidemiological studies; however, relatively few applications are identified. One reason for its low usage is the lack of knowledge and tools for these methods among researchers. To expand existing evaluation methods, based on the QBA principles, three indicators are proposed. One is the relative bias that quantifies the bias direction through its signs and the bias magnitude through its quantity. The second is the critical point of positive test proportion in case of a misclassification bias that is equal to zero. The third is the bound of positive test proportion equal to adjusted prevalence at misclassification bias level α. These indicators express the magnitude, direction and uncertainty of the misclassification bias of prevalence estimates, respectively. Using these indicators, it was found that slight oscillations of the positive test proportion within a certain range can lead to substantial increases in the misclassification bias. Hence, researchers should account for misclassification error analytically when interpreting the significance of adjusted prevalence for epidemiological decision making. This highlights the importance of applying QBA to these analyses. In this article, we have used three real-world cases to illustrate the characteristics and calculation methods of presented indicators. To facilitate application, an Excel-based calculation tool is provided.
The Origins and Risk Factors for Serotype-2 Vaccine-Derived Poliovirus Emergences in Africa During 2016–2019
Authors: Gray Elizabeth J , Cooper Laura V , Bandyopadhyay Ananda S , Blake Isobel M , Grassly Nicholas C
Published: January 2023

Serotype 2 oral poliovirus vaccine (OPV2) can revert to regain wild-type neurovirulence and spread to cause emergences of vaccine-derived poliovirus (VDPV2). After its global withdrawal from routine immunization in 2016, outbreak response use has created a cycle of VDPV2 emergences that threaten eradication. We implemented a hierarchical model based on VP1 region genetic divergence, time, and location to attribute emergences to campaigns and identify risk factors. We found that a 10 percentage point increase in population immunity in children younger than 5 years at the campaign time and location corresponds to a 18.0% decrease (95% credible interval [CrI], 6.3%–28%) in per-campaign relative risk, and that campaign size is associated with emergence risk (relative risk scaling with population size to a power of 0.80; 95% CrI, .50–1.10). Our results imply how Sabin OPV2 can be used alongside the genetically stable but supply-limited novel OPV2 (listed for emergency use in November 2020) to minimize emergence risk.
An extensively validated whole-cell biosensor for specific, sensitive and high-throughput detection of antibacterial inhibitors targeting cell-wall biosynthesis
Authors: Galarion Luiza H , Mitchell Jennifer K , Randall Christopher P , O’Neill Alex J
Published: January 2023

Background

Whole-cell biosensor strains are powerful tools for antibacterial drug discovery, in principle allowing the identification of inhibitors acting on specific, high-value target pathways. Whilst a variety of biosensors have been described for detecting cell-wall biosynthesis inhibitors (CWBIs), these strains typically lack specificity and/or sensitivity, and have for the most part not been rigorously evaluated as primary screening tools. Here, we describe several Staphylococcus aureus CWBI biosensors and show that specific and sensitive biosensor-based discovery of CWBIs is achievable.

Methods

Biosensors comprised lacZ reporter fusions with S. aureus promoters (PgltB, PilvD, PmurZ, PoppB, PORF2768, PsgtB) that are subject to up-regulation following inhibition of cell-wall biosynthesis. Induction of biosensors was detected by measuring expression of β-galactosidase using fluorogenic or luminogenic substrates.

Results

Three of the six biosensors tested (those based on PgltB, PmurZ, PsgtB) exhibited apparently specific induction of β-galactosidase expression in the presence of CWBIs. Further validation of one of these (PmurZ) using an extensive array of positive and negative control compounds and conditional mutants established that it responded appropriately and uniquely to inhibition of cell-wall biosynthesis. Using this biosensor, we established, validated and deployed a high-throughput assay that identified a potentially novel CWBI from a screen of >9000 natural product extracts.

Conclusions

Our extensively validated PmurZ biosensor strain offers specific and sensitive detection of CWBIs, and is well-suited for high-throughput screening; it therefore represents a valuable tool for antibacterial drug discovery.
Pharmacokinetics/pharmacodynamics and therapeutic drug monitoring of ceftazidime/avibactam administered by continuous infusion in patients with MDR Gram-negative bacterial infections
Authors: Fresan D , Luque S , Benítez-Cano A , Sorlí L , Milagro Montero M , De-Antonio M , Prim N , Vega V , Horcajada J P , Grau S
Published: January 2023

Background

Therapeutic drug monitoring (TDM) of β-lactams in critically ill patients has been correlated with better clinical outcomes. Evidence on TDM of newer β-lactams such as ceftazidime/avibactam administered by continuous infusion (CI) is very limited.

Objectives

To describe our experience with TDM of ceftazidime/avibactam and pharmacokinetic/pharmacodynamic (PK/PD) target attainment in patients with MDR bacterial infections. Clinical outcomes of ceftazidime/avibactam administered by CI were also assessed.

Methods

Patients treated with ceftazidime/avibactam administered by CI and undergoing TDM of ceftazidime plasma concentrations were included. Blood samples were obtained as part of the TDM program. The PK/PD therapeutic target of ceftazidime/avibactam was defined as 100%fT > 4 × MIC of the causative pathogen, and 100%fT > 10 × MIC was considered overexposure. Dose changes were made according to the TDM results.

Results

Thirty-one patients were included. Ceftazidime/avibactam total daily doses ranged from 1 g/0.25 g to 6 g/1.5 g. Twenty-six patients (83.9%) achieved a 100%fT > 4 × MIC, 15 (48.4%) of which were overexposed (100%fT > 10 × MIC). Dose reduction was suggested in 16/28 (57.1%) patients and dose maintenance in 12/28 (42.9%). Overall clinical cure was observed in 21 (67.7%) patients, and 18 of these (85.7%) achieved a 100%fT > 4 × MIC.

Conclusions

Administering ceftazidime/avibactam by CI enabled the desired PK/PD target to be achieved in a large proportion of patients, even at lower doses than those recommended for a 2 h extended infusion. We suggest that the use of CI with TDM may be a useful tool for reducing initial doses, which could help to reduce antimicrobial-related adverse effects and treatment costs.
Characterization of Samples with Minor P3 Peak Elevations in a High Pressure Liquid Chromatography System for HbA1c: Contributions of Hemoglobin Variants and Storage Conditions
Authors: Zheng Yu Zi , Kovacic Cassandra , Potz Julie , McCale Mitchell , Ondrejka Sarah L , Colón-Franco Jessica M
Published: January 2023

Background

In the Bio-Rad D-100TM (Bio-Rad, Hercules, CA) HPLC system for hemoglobin A1c (HbA1c) measurement, 7 peaks elute: HbA1a, HbA1b, HbF, LA1c, HbA1c, P3, and HbA0. HbA1c is calculated from the ratio of the HbA1c peak area to the total area, excluding HbF and peaks after HbA0, if present. A P3 peak >10% flags for potential interferences.

Methods

We investigated 26 samples with elevated P3 peaks to determine the presence of hemoglobin variants, the effect of prolonged specimen storage in the P3 peak. The relationship between the P3 peak and the HbA1c concentration were also investigated.

Results

No hemoglobin variants were identified when the P3 peak was <14% (n = 14). Hemoglobin variants were detected in 7 of 12 with a P3 peak between 17.0% and 28.2%. Sample storage at room temperature had minimum impact on the P3 peak area (n = 20); the average P3 bias was −0.5 (−8.1% bias) after 3 days and 0.6 (12.2% bias) after 5 days. P3 increased with increasing HbA1c concentrations in samples with P3 < 10%. Most samples with P3 above 10 and up to 14% had marked HbA1c elevations.

Conclusions

Minor elevations of the P3 peak were due only in part to hemoglobin variants, particularly in samples with P3 above 17% (below 28.2%). These elevations caused a decrease in HbA1c, whether hemoglobin variants are detected or not. Prolonged storage at room temperature did not cause P3 peaks to increase above 10%.
Discussion and Optimization of the Male Breast Cancer Patient Experience
Authors: Constantinou Niki , Marshall Colin , Marshall Holly
Published: January 2023

Breast cancer in men is rare and often overlooked as there is a misconception that it is a gendered disease that affects women only. The feminization, or “pinkification,” of the disease has been socially constructed to raise awareness, improve screening, and empower women but has not addressed the occurrence of the illness in men. Men may therefore experience unique psychosocial difficulties when faced with a disease that predominantly affects women, including feelings of disbelief and embarrassment that impact their sense of self and challenge their masculinity. The lack of mammographic screening in men, lack of public awareness, and the shame that develops during the time of diagnosis can result in treatment avoidant behaviors, a delayed presentation, and worse prognosis in men. Although male breast cancer (MBC) is uncommon, the incidence is increasing; therefore, efforts should be made to enhance education for health care professionals and the general public in order to lessen the stigma, with the goal of improving outcomes. Furthermore, special attention to the unique medical needs and hurdles encountered by transgender males can break down health care barriers in this marginalized patient population. This article offers male perceptions on breast cancer, the psychosocial implications of being diagnosed with a gendered disease, and suggestions on how to improve the MBC experience.
Mice inflammatory responses to inhaled aerosolized LPS: effects of various forms of human alpha1-antitrypsin
Authors: Sivaraman Kokilavani , Wrenger Sabine , Liu Bin , Schaudien Dirk , Hesse Christina , Gomez-Mariano Gema , Perez-Luz Sara , Sewald Katherina , DeLuca David , Wurm Maria J , Pino Paco , Welte Tobias , Martinez-Delgado Beatriz , Janciauskiene Sabina
Published: January 2023

Rodent models of lipopolysaccharide (LPS)–induced pulmonary inflammation are used for anti-inflammatory drug testing. We aimed to characterize mice responses to aerosolized LPS alone or with intraperitoneal (i.p.) delivery of alpha1-antitrypsin (AAT). Balb/c mice were exposed to clean air or aerosolized LPS (0.21 mg/mL) for 10 min per day, for 3 d. One hour after each challenge, animals were treated i.p. with saline or with (4 mg/kg body weight) one of the AAT preparations: native (AAT), oxidized (oxAAT), recombinant (recAAT), or peptide of AAT (C-36). Experiments were terminated 6 h after the last dose of AATs. Transcriptome data of mice lungs exposed to clean air versus LPS revealed 656 differentially expressed genes and 155 significant gene ontology terms, including neutrophil migration and toll-like receptor signaling pathways. Concordantly, mice inhaling LPS showed higher bronchoalveolar lavage fluid neutrophil counts and levels of myeloperoxidase, inducible nitric oxide synthase, IL-1β, TNFα, KC, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Plasma inflammatory markers did not increase. After i.p. application of AATs, about 1% to 2% of proteins reached the lungs but, except for GM-CSF, none of the proteins significantly influenced inflammatory markers. All AATs and C-36 significantly inhibited LPS-induced GM-CSF release. Surprisingly, only oxAAT decreased the expression of several LPS-induced inflammatory genes, such as Cxcl3, Cd14, Il1b, Nfkb1, and Nfkb2, in lung tissues. According to lung transcriptome data, oxAAT mostly affected genes related to transcriptional regulation while native AAT or recAAT affected genes of inflammatory pathways. Hence, we present a feasible mice model of local lung inflammation induced via aerosolized LPS that can be useful for systemic drug testing.
The impact ofADRB2polymorphisms on immune responses and norepinephrine-induced immunosuppression
Authors: Stolk Roeland F , Bruse Niklas , ter Horst Rob , Jansen Aron , Ricaño Ponce Isis , Gerretsen Jelle , van der Hoeven Johannes , Kumar Vinod , Netea Mihai G , Pickkers Peter , Kox Matthijs
Published: January 2023

Rationale

To evaluate whether common nonsynonymous variants [single-nucleotide polymorphisms (SNPs) or SNP haplotypes] in the β2-adrenergic receptor render subjects more susceptible to norepinephrine-induced immunosuppression and whether they are associated with dysregulated ex vivo and in vivo inflammatory responses.

Methods

Peripheral blood mononuclear cells from healthy volunteers (main cohort: n = 106, secondary cohort: n = 408) were ex vivo stimulated with various stimuli and production of cytokines was assessed. Additionally, ex vivo modulation of cytokine production by norepinephrine was evaluated in the main cohort. Volunteers from the main cohort also underwent experimental endotoxemia (administration of 1 ng/kg lipopolysaccharide), during which in vivo plasma cytokine concentrations and clinical inflammatory parameters were measured. Subjects were genotyped, common SNPs in the ADRB2 gene were extracted (rs1042711, rs1042713, and rs1042714), and the presence of haplotypes was identified (CysGlyGln, CysArgGln, and ArgGlyGlu).

Results

In both cohorts, presence of ADRB2 SNPs or haplotypes was not associated with altered ex vivo cytokine responses. Norepinephrine attenuated production of the proinflammatory cytokines TNF and IL-6 [−26% (−22% to −30%) and −14% (−9% to −18%), respectively, both P < 0.0001] and enhanced release of the anti-inflammatory IL-10 [+9% (+3% to +15%), P = 0.003]. These effects were not modulated by the presence of ADRB2 SNPs or haplotypes (all P values >0.37). In addition, no influence of SNPs or haplotypes on in vivo cytokine concentrations or clinical inflammatory parameters was observed (P values >0.14).

Conclusions

Common nonsynonymous variants in the ADRB2 gene influence neither ex vivo cytokine production or norepinephrine-mediated immunosuppression nor the systemic in vivo inflammatory response induced by lipopolysaccharide administration in healthy volunteers.