bluuebunny/crossref_metadata_2025 huggingface dataset:
Customization effort estimation of Microsoft ERP projects
Authors: Yousaf Tameem , Afzal Malik Ali , Daud Marriam
Published: August 2024

The enterprise resource planning (ERP) software market is rapidly growing due to its potential in aiding organizations to streamline their business processes and enhance workforce productivity. However, ERP customization projects often encounter delays in schedules and exceed budgets mainly because estimations of project customization effort and duration are typically carried out using ad-hoc methods. This study aims to construct and validate a customization effort estimation (CEE) model tailored for ERP projects employing Microsoft Dynamics 365 (D365) customization. To achieve this, six critical factors that impact CEE in D365 projects are identified. Subsequently, an industry-wide survey is conducted to determine the relative significance of these factors and to establish their weights for both simple and complex variants. The proposed model D365CustomizePro is created through the application of stepwise multiple linear regression and then validated through the leave-one-out cross-validation technique based on data collected from 21 real-life D365 projects undertaken at a software house. The estimation accuracy of D365CustomizePro is compared with the estimation accuracy achieved by using two different well-known effort estimation techniques, i.e. expert judgment and COCOMO II (algorithmic estimation model). Results reveal that D365CustomizePro exhibits better estimation accuracy vis-á-vis both expert judgment and COCOMO II.
Peripheral Blood Eosinophilia at Diagnosis of Inflammatory Bowel Disease Is Associated With Severe Disease Course: A Nationwide Study From the epi-IIRN Cohort
Authors: Yerushalmy-Feler Anat , Lujan Rona , Loewenberg Weisband Yiska , Greenfeld Shira , Ben-Tov Amir , Ledderman Natan , Matz Eran , Dotan Iris , Lev-Tzion Raffi , Goren Idan , Turner Dan , Cohen Shlomi
Published: August 2024

Background and Aims

We conducted this nationwide study to evaluate the association between peripheral blood eosinophilia (PBE) and long-term outcomes in children and adults with inflammatory bowel diseases (IBDs).

Methods

Data from the Epidemiology Group of the Israeli IBD Research Nucleus (epi-IIRN) cohort, a validated population-based IBD database, included patients diagnosed between 2005 and 2020, who had an eosinophil count recorded at diagnosis, and non-IBD controls. PBE was defined as an eosinophil count of >0.5 × 109/L. Severe disease course was defined as corticosteroid dependency, use of ≥2 biologics from different classes, or surgery. Time-to-outcomes, including severe disease course, was determined by Cox proportional hazard models.

Results

This study included 28 133 patients (15 943 Crohn’s disease [CD] and 12 190 ulcerative colitis [UC]) and 28 724 non-IBD controls. The prevalence of PBE was 13% in the IBD group and 5% in the control group (p < 0.001). PBE was more prevalent in UC (16.1%) compared to CD (10.6%, odds ratio [OR] = 1.52, 95% confidence interval [CI], 1.42-1.63; p < 0.001) and in pediatric-onset (23.5%) compared to adult-onset (11%) IBD (OR = 2.14, 95% CI, 1.97-2.31; p < 0.001). In a multivariate analysis, PBE was a predictor of severe disease course in IBD (hazard ratio [HR] = 1.49, 95% CI, 1.38-1.62, p < 0.001). PBE also predicted time-to-hospitalization (HR = 1.24, 95% CI, 1.19-1.30), use of corticosteroids (HR = 1.32, 95% CI, 1.28-1.36), corticosteroid dependency (HR = 1.37, 95% CI, 1.31-1.43), and need for biologics (HR = 1.27, 95% CI, 1.21-1.33).

Conclusions

In this largest nationwide study, PBE predicted severe IBD course. These findings support the use of PBE as a marker of adverse outcomes of IBD and as a potential target for future therapies.
Diverticular disease and risk of incident major adverse cardiovascular events: a nationwide matched cohort study
Authors: Forss Anders , Ma Wenjie , Thuresson Marcus , Sun Jiangwei , Ebrahimi Fahim , Bergman David , Olén Ola , Sundström Johan , Ludvigsson Jonas F
Published: August 2024

Background

An increased risk of cardiovascular disease (CVD) has been reported in patients with diverticular disease (DD). However, there are knowledge gaps about specific risks of each major adverse cardiovascular event (MACE) component.

Methods and results

This nationwide cohort study included Swedish adults with DD (1987–2017, N = 52 468) without previous CVD. DD was defined through ICD codes in the National Patient Register and colorectal histopathology reports from the ESPRESSO study. DD cases were matched by age, sex, calendar year, and county of residence to ≤5 population reference individuals (N = 194 525). Multivariable-adjusted hazard ratios (aHRs) for MACE up until December 2021 were calculated using stratified Cox proportional hazard models. Median age at DD diagnosis was 62 years, and 61% were females. During a median follow-up of 8.6 years, 16 147 incident MACE occurred in individuals with DD and 48 134 in reference individuals [incidence rates (IRs)= 61.4 vs. 43.8/1000 person-years], corresponding to an aHR of 1.24 (95%CI = 1.22–1.27), equivalent to one extra case of MACE for every 6 DD patients followed for 10 years. The risk was increased for ischaemic heart disease (IR = 27.9 vs. 18.6; aHR = 1.36, 95%CI = 1.32–1.40), congestive heart failure (IR = 23.2 vs. 15.8; aHR = 1.26, 95%CI = 1.22–1.31), and stroke (IR = 18.0 vs. 13.7; aHR = 1.15, 95%CI = 1.11–1.19). DD was not associated with cardiovascular mortality (IR = 18.9 vs. 15.3; aHR = 1.01, 95%CI = 0.98–1.05). Results remained robust in sibling-controlled analyses.

Conclusions

Patients with DD had a 24% increased risk of MACE compared with reference individuals, but no increased cardiovascular mortality. Future research should confirm these data and examine underlying mechanisms and shared risk factors between DD and CVD.
The cold temperature associated with new-onset heart failure after incorporating dynamic status of multimorbidity: nationwide cohort, Taiwan 2012–2019
Authors: Chen Dong-Yi , Chang Shu-Hao , Huang Wen-Kuan , Hsieh I Chang , See Lai-Chu
Published: August 2024

Aims

Cold temperatures are known to affect heart failure (HF) hospitalizations, but the dynamic status of multi-morbidity of HF was rarely incorporated. We investigated the relationship between temperature and new-onset HF by risk strata.

Methods and results

This nationwide cohort study analysed daily data on ambient temperature, the dynamic status of risk factors (age, diabetes, chronic obstructive pulmonary disease, coronary artery disease, chronic kidney disease, hypertension, myocardial infarction, and atrial fibrillation), and new-onset HF among the Taiwan population from 2012 to 2019. Poisson regression, Austin’s algorithm, and classification and regression tree (CART) were used to determine risk strata and obtain the predicted HF rate. 148 708 patients developed new-onset HF over 152.52 million person-years. Three risk strata for HF were identified: Stratum 1 was predominantly those without any comorbidity (89.9%); Stratum 2 was those aged 60–69 with 2–3 comorbidities or aged 70+ with 1–2 comorbidities (9.0%), and Stratum 3 was those aged 70+ and had four or more comorbidity (1.1%). The HF incidence rates for these three strata were 25.54, 555.27, and 2315.52 per 100 000 person-years, respectively. The R2 of the Poisson regression with the three risk strata and the daily minimum temperature on the ln HF incidence rates was 77.99%. The risk of HF increased as temperatures decreased, and the slopes were 1.032, 1.040, and 1.034 for Strata 1–3, respectively. The rate ratios of HF at the winter median temperature of 17°C vs. the summer median temperature of 29°C were 1.45, 1.58, and 1.49 for Strata 1–3, respectively. Cross-validation reveals a good fit and predicted HF rates by ambient temperature for the three strata were provided.

Conclusion

Cold temperatures are associated with an increased risk of new-onset HF. Stratum 2 (aged 60–69 with 2–3 comorbidities or aged 70+ with 1–2 comorbidities) are particularly susceptible to cold-related new-onset HF.
Do sympatric catfish radiations in Lake Tanganyika show eco-morphological diversification?
Authors: Peart Claire R , Bills Roger , Newton Jason , Near Thomas J , Day Julia J
Published: August 2024

Adaptive radiation is characterized by eco-morphological differentiation, in which niche partitioning has been shown to be a central response to natural selection during the diversification of animal clades. This process is suggested to have generated the exceptional biodiversity in the East African rift lakes; however, aside from the cichlid fishes, the nature of the divergence, over time, or among species is less clear in the other radiations. To address this, we focus on two distantly related sympatric Lake Tanganyika catfish clades, the genus Synodontis, considered to be Müllerian mimics, and the subfamily Claroteinae. We investigate to what extent, if any, these radiations have undergone eco-morphological diversification. We place these radiations in a common phylogenetic context, and test for morphological divergence and trophic niche partitioning using novel trait data and stable isotope signatures. Diversification of both catfish clades was recent, with the Synodontis radiation synchronized in time with individual genera within the claroteine radiation, suggesting initial diversification was facilitated by lake basin dynamics and/or lake level fluctuations. There is evidence for eco-morphological diversification within the claroteine radiation, as inferred from observed morphological disparity and divergence in diet both between and within genera; however, several species show significant overlap in dietary isotopic signatures. In contrast, the Synodontis radiation has greater overlap between taxa both in morphology and in isotopic signatures potentially indicating niche conservatism, suggesting different selective forces may be driving these radiations.
Young people’s views and experience of diet-related inequalities in England (UK): a qualitative study
Authors: Er Vanessa , Crowder Mary , Holding Eleanor , Woodrow Nicholas , Griffin Naomi , Summerbell Carolyn , Egan Matt , Fairbrother Hannah
Published: August 2024

Inequalities in diets contribute to overall inequalities in health. Economic inequality and inequalities in access to healthy food are key drivers of poor diet and ill health among young people (YP). Despite mounting evidence of structural barriers to healthy eating, less is known about how YP view and experience these inequalities where they live, and how to address them. To explore YP’s perspectives on the drivers of diet-related health inequalities, we conducted three interlinked focus groups with YP aged 13–21 years from six youth groups across three geographical areas in England. We analysed the data inductively and deductively using reflexive thematic analysis and generated themes by examining how social structure, context and agency interact and impact YP’s diet. YP were aware of how inequalities in employment conditions impact their families’ income and ability to eat a healthy diet. They cited the high availability of hot food takeaways in their local areas as a significant barrier to healthy eating but did not support closing or restricting these outlets. They held strong views on policies to tackle diet inequality and showed a nuanced understanding of the strengths and limitations of universal and targeted approaches. Our study showed that YP have an awareness and understanding of food as important in relation to health, and of diet-related inequalities. However, further efforts are needed to shape and promote policies that resonate with YP and address both their health and wider social concerns.
O01 Antimicrobial resistance and death certification: are we there yet?
Authors: Baltas Ioannis , Rawson Timothy M , Houston Hamish , Grandjean Louis , Pollara Gabriele
Published: August 2024

Background

The impact of antimicrobial resistance (AMR) on death at the patient level remains challenging to estimate. We aimed to characterize AMR-attributable deaths in a large UK centre through death certification.

Methods

This was a retrospective study of all patients who died in University College London Hospitals NHS Foundation Trust in 2022 (N=758). Clinical records of participants with positive microbiological samples within 28 days of death were reviewed by two independent investigators. AMR-attributable deaths were defined using a newly proposed standardized patient-level definition after consensus agreement between the two investigators. A third investigator acted as a tiebreaker in cases of disagreement.

Results

Overall, infection was the underlying cause of death for 11.7% (89/758) of participants and was implicated in the pathway that led to death in 41.1% (357/758) of cases. The most common infection syndromes leading to death as documented on the medical certificate of confirmation of death (MCCD) were respiratory tract infections, sepsis and COVID-19. In total, 4.2% (32/758) of all deaths were AMR-attributable. AMR-attributable deaths were more commonly recorded in patients admitted under haematology (7.5%, 9/120) and in younger patients (median age 67 versus 72, P=0.01). The median time from the index sample collection until death was 4.5 days (IQR 2–10.5 days). The majority of AMR-attributable deaths (56.3%, 18/32) were caused by treatment failure and subsequent treatment delay caused by intrinsic resistance mechanisms, primarily by Enterococcus faecium (38.9%, 7/18), Enterobacterales carrying repressed chromosomal AmpCs (27.7%, 5/18) and Pseudomonas aeruginosa (22.2%, 4/18). On the contrary, a minority of AMR-attributable deaths (43.7%, 14/32) were caused by acquired resistance mechanisms, primarily derepressed AmpCs (28.6%, 4/14) and ESBLs (21.4%, 3/14). The median time to effective treatment was 32 h 15 min and did not differ significantly between the two groups. Only 62.5% (20/32) of AMR-attributable deaths as judged by study investigators had infection recorded on the MCCD. AMR was not recorded as a cause of death in any of the patients, including the 14 patients who were deemed to have suffered deaths due to acquired resistance by the study investigators.

Conclusions

Infection and AMR were significant causes of death in this cohort, yet there significantly underreported during death certification. In a low incidence setting for AMR, delays in treatment and AMR-attributable mortality due to intrinsic resistance mechanisms (expected phenotypes) were more common compared with acquired resistance mechanisms.
P23 Advance market commitment for point of care diagnostic focused on neonatal sepsis: estimating costs and effectiveness
Authors: Bansal Akhil , Howes Adam , Arih Ilona
Published: August 2024

Background

Antimicrobial resistance (AMR) is a pressing global health concern, responsible for millions of deaths every year. Overuse and misuse of antimicrobials is a significant driver of AMR and is partly driven by a lack of decision-relevant and timely diagnostic tests to guide treatment. Point of care tests (POCT) would be of great public health benefit for neonatal sepsis, which refers to systemic life-threatening infections in newborns in their first 28 days of life. Neonatal sepsis, for which over- and inappropriate prescription of antibiotics are very high, affects 1.3 to 3.9 million neonates and accounts for nearly a quarter of all neonatal deaths. However, due to insufficient market incentives and revenue guarantee for developers, research and development pipelines are stagnant and no such POCT exists. One proposed solution is an advanced market commitment (AMC), a form of ‘pull incentive’ that would aim to ‘pull’ a new POCT to market. In an AMC, donors commit to a fund from which a specified subsidy is paid per unit purchased by low income countries until the fund is exhausted. This aims to strengthen suppliers’ incentives to invest in research, development and capacity.

Methods

This study modelled the costs and outcomes of an AMC for a neonatal sepsis POCT that would seek to identify the presence or absence of sepsis. Modelled for the Indian public healthcare system, the test was conceived as an adjunct to clinical judgement where there is diagnostic uncertainty if a neonate has sepsis. The POCT was compared with current best practice. Benefits of increased identification of neonatal sepsis and decreased burden of AMR were considered; cost of diagnostic tests and antibiotic treatment were considered. Cost-effectiveness and incremental cost-effectiveness were calculated in cost per disability adjusted life year (DALY), from both the perspective of the Indian healthcare system and investors to an AMC.

Results

From our cost-effectiveness model, a POCT would have an incremental cost-effectiveness of $93.56/DALY (compared with current clinical practice) for the Indian healthcare system, with a cost-effectiveness of $5.9/DALY for donors to an AMC. On sensitivity analysis, the cost benefit analysis is contingent on a test with sufficiently high specificity and sensitivity and varies depending on estimated AMR burden.

Conclusions

Although a novel market incentive with some uncertainty in model parameters, an AMC for a neonatal sepsis POCT may be highly effective and cost-effective from both a global health and AMR perspective.
P29 Understanding penicillin allergy assessment and delabelling massive open online community
Authors: Powell Neil , Quinn Alicia , Weaving Chris , Sandoe Jonathan ,   educational team, Bhogal Rashmeet , Elkhalifa Shuayb , Blumenthal Kimberly , Sneddon Jacqueline , Tonkin-Crine Sarah , Trubiano Jason , Stone Cosby , Stollings Joanna
Published: August 2024

Background

PenA records are associated with antibiotic prescribing that is potentially less effective and more harmful. The paucity of allergy specialists worldwide has prompted non-allergist delivered penicillin allergy delabelling (PADL). To facilitate non-allergist delivery of PADL, a massive open online course (MOOC) was developed with objectives to raise awareness and provide healthcare workers with the requisite knowledge and skills to deliver PADL.

Methods

Developmental support and funding for the MOOC was provided by BSAC. An educator panel was convened with topic experts from the USA, UK and Australia representing infectious diseases, allergy, pharmacy, medical microbiology and health psychology. Key learning objectives were defined, the course structure was agreed, and content was developed and peer reviewed by panel members and BSAC. The MOOC was launched and hosted on FutureLearn. Data on learner numbers, demographics and feedback were collected to measure course uptake and effectiveness in meeting the objectives.

Results

The 2 week course entitled ‘Understanding Penicillin Allergy Assessment and Delabelling’ with 6 h of learning was published 20 November 2023 on FutureLearn. The course was accredited by the Royal College of Pathologists for 6 CPD points. As of 10 April 2024, there were 1599 learners from 119 countries, which were: 16% medical doctors, 2% surgical doctors, 3% other doctors, 18% pharmacists, 11% nurses, 34% students, 1% physicians associate (PA), 1% nurses associate and 15% other. The top five countries by joiner count are UK (466), India (118), Pakistan (60), Italy (44) and Egypt (44). Of those that completed the course and responded to the end-of-course survey, 40/65 (62%) rated the course better than expected, 24 (37%) had their expectations met and 1 (1.5%) rated the course worse than expected. Overall, 61 (94%) gained new knowledge or skills, 29 (45%) applied their learnings and 49 (75%) reported sharing their learnings with others. Examples of learner comments:

“Truly, the best penicillin allergy explanation I have ever come across. So detailed and well illustrated. Thank you!”

“Fantastic course! I’m going to recommend every health care professional at my organisation complete this as part of my Antimicrobial Stewardship training. Thank you for putting it together.”

Conclusions

The MOOC has reached a broad range of learners from a variety of disciplines in a range of countries globally. The reception has been very positive, with comments stating that knowledge of penicillin allergies had improved and applied to improve local PADL services—a direct indication of meeting the learning outcomes.
P37 Molecular characterization of resistance and heteroresistance to cefiderocol in clinical Gram-negative isolates
Authors: Young Francesca , Watson Celeste , Rofael Sylvia , Wey Emmanuel , Balakrishnan Indran
Published: August 2024

Background

Treatment failure with cefiderocol has been attributed to heteroresistance, a phenomenon whereby clinically susceptible bacterial populations contain a minority resistant subpopulation.

Objectives

To compare three antimicrobial susceptibility tests (AST) for detecting cefiderocol resistance/heteroresistance; to investigate the population dynamics of heteroresistant isolates in response to antibiotic exposure; and to characterize the molecular mechanisms underlying resistance and heteroresistance to cefiderocol.

Methods

Forty-three Gram-negative clinical isolates were screened for cefiderocol susceptibility using disc diffusion, Etest and broth microdilution (BMD), according to EUCAST guidelines. Eleven isolates demonstrating heteroresistance were serially passaged in iron-depleted Mueller–Hinton II broth containing sub-inhibitory concentrations of cefiderocol (0.25xMIC) and then further passaged in the absence of antibiotic selection pressure. Changes in MIC and frequency of the heteroresistant phenotype were determined using Etests. Fourier transform infrared and MALDI-TOF spectroscopy were used to compare the molecular differences between resistant, heteroresistant and susceptible phenotypes.

Results

Etest assays significantly underestimated cefiderocol resistance (P<0.001), with 32% categorical agreement, compared with 75% for disc diffusion, relative to the gold-standard BMD method. However, BMD is poor at detecting heteroresistance, identifying only 1/11 (9%), whilst Etests identified 3/11 (27%) (Figure 1). After passages under antibiotic selection pressure, 2/11 (18%) increased in MIC (mean: 3-fold). After subsequent antibiotic-free passages, 4/11 (36%) demonstrated increased MICs. Interestingly, this contrasted with isolates only passaged in antibiotic-free medium, in which 8/11 (72%) decreased in MIC, reverting to the more susceptible parental phenotypes. Molecular analyses highlighted characteristic differences between the spectra of parental populations and subpopulations, indicating complex mechanistic modifications in carbohydrate, lipid and protein complexes.

Conclusions

Detection of clinically significant heteroresistance indicates that resistant subpopulations may exist amongst a phenotypically susceptible population, underscoring the need for heteroresistance detection methods in clinical settings. The heteroresistant phenotype was unstable and reverted to susceptibility unless exposed to cefiderocol. Interestingly, isolates exposed to antibiotic pressure often exhibit increases in MIC only after antibiotic removal. These findings suggest that cefiderocol exposure primes isolates for later development of resistance. Spectroscopic analyses confirm the presence of characteristic molecular fingerprints associated with cefiderocol susceptibility, which may inform our understanding of resistance.
Extrusion can ameliorate negative effects of molecular structures of brewer’s spent grain on energy contents and amino acid digestibility in growing pigs
Authors: Xie Yueqin , Liu Dongyun , Liu Yuxiao , Liu Yang , Tang Jiayong , Liu Guangmang , Zhao Hua , Tian Gang , Chen Xiaoling , Cai Jingyi , Jia Gang
Published: August 2024

The objectives of this study were to investigate the effects of extrusion on the chemical compositions, surface structure, and molecular structure of brewer’s spent grain (BSG), as well as to determine the digestible energy (DE), metabolizable energy (ME), apparent total tract digestibility (ATTD) of nutrients and energy, and amino acid (AA) digestibility of extruded BSG when fed to growing pigs. Firstly, we determined the changes in chemical compositions and molecular structure of both non-extruded and extruded BSG. In Exp. 1, eighteen growing pigs were fed three different diets including one corn-soybean meal basal diet and two experimental diets containing 20% BSG with or without extrusion. Feces and urine were collected to determine the ATTD of nutrients and energy, DE, and ME of extruded or non-extruded BSG. In Exp. 2, eighteen growing pigs were fed three different diets including 30% BSG with or without extrusion, and an N-free diet. Ileal digesta was collected through the slaughter method to determine the apparent ileal digestibility (AID) and standardized ileal digestibility (SID) of AA of extruded or non-extruded BSG. The results showed that extrusion reduced the neutral detergent fiber, hemicellulose and cellulose contents in BSG, and increased the Arg, Asp, Glu, Ser, Tyr, total indispensable AA and total AA contents of BSG, altered the surface structure of BSG, increased the peak absorbance in amide I and amide II height, amide II and amide (I+II) area, α-helix height, decreased β-sheet height, and weakened band intensities in cellulosic compounds (CELC) area, structural carbohydrates (SCHO) area, carbohydrates area (CHO) peak 2 and 3 height, the area ratio of CELC: CHO and CELC: SCHO. Moreover, DE and ME values and ATTD of energy, dry matter, crude protein, acid detergent fiber, neutral detergent fiber, cellulose and hemicellulose increased (P < 0.05) when pigs were fed extruded BSG diets. The AID and SID of Arg, His, Lys, Val and Gly increased, whereas the AID and SID of Ile and Leu decreased when pigs were fed extrusion diets (P < 0.05). Our study found that the ATTD of nutrients and AA digestibility in pigs were positively correlated with the molecular structure of proteins, and negatively correlated with the molecular structure of carbohydrates (P < 0.05). These findings suggested that extrusion had the potential to improve the nutrient digestibility of BSG by altering its chemical compositions, surface structure, and molecular structure.
In vitro and in silico study of biological effects on cancer cells in the presence of metallic materials during radiotherapy
Authors: Nagano Takuya , Matsuya Yusuke , Kaida Atsushi , Nojima Hitomi , Furuta Takuya , Sato Kaoru , Yoshimura Ryoichi , Miura Masahiko
Published: August 2024

X-ray therapy aims to eliminate tumours while minimizing side effects. Intense mucositis is sometimes induced when irradiating the oral cavity with a dental metal crown (DMC). However, the underlying mechanisms of such inducing radiosensitization by DMC remain uncertain. This study explored the radiosensitizing mechanisms around DMCs in an interdisciplinary approach with cell experiments and Monte Carlo simulation with the PHITS code. Clonogenic survival and nuclear 53BP1 foci of a cell line derived from cervical cancer cells (HeLa cells) were measured post-irradiation with therapeutic X-rays near high-Z materials such as Pb or Au plates, and the experimental sensitizer enhancement ratio (SER) was obtained. Meanwhile, the dose enhancement ratio (DER) and relative biological effectiveness for DNA damage yields were calculated using the PHITS code, by considering the corresponding experimental condition. The experiments show the experimental SER values for cell survival and 53BP1 foci near metals are 1.2–1.4, which agrees well with the calculated DER values. These suggest that the radiosensitizing effects near metal are predominantly attributed to the dose increase. In addition, as a preclinical evaluation, the spatial distributions of DER near DMC are calculated using Computed Tomography Digital Imaging and Communications in Medicine (CT-DICOM) data and a simple tooth model. As a result, the DER values evaluated using the CT-DICOM data were lower than those from a simple tooth model. These findings highlight the challenge of evaluating radiosensitizing effects near DMCs using Digital Imaging and Communications in Medicine (DICOM) images due to volume-averaging effects and emphasize the need for a high-resolution (<1 mm) dose assessment method unaffected by these effects.
MegaAppendix: a rare case of mantle cell lymphoma in an appendix presented as volvulus
Authors: Mamukadze Irada , Gabel Shelley , Park Sean K , Jackson Mackenzie , Nguyen Long
Published: August 2024

Mantle cell lymphoma (MCL), representing 5% of cases, is an aggressive B-cell non-Hodgkin lymphoma. Rarely, it can spread to other areas. This case illustrates a unique occurrence of MCL involving the appendix, leading to obstructive symptoms. Additionally, its presentation as volvulus added complexity to diagnosis and treatment. A 72-year-old man with a history of MCL came to the ER with right lower quadrant abdominal pain and nausea for 7 days. A computed tomography scan showed a swirling sign, concerning for volvulus. The patient required emergent surgery for exploratory laparotomy. Intraoperatively, the patient was found to have an enlarged appendix measuring 16.5 cm in length and 5 cm in diameter. An appendectomy was performed, and the pathology was confirmed to be MCL. This is a rare case of MCL presenting in the appendix as a volvulus, resulting in obstructive symptoms. This distinctive manifestation posed significant challenges in diagnosis and management. Appreciating such cases is pivotal for accurate diagnosis and effective medical and surgical interventions for this aggressive lymphoma subtype.
MEMBRANE PROTEIN 1 encoding an amino acid transporter confers resistance to blast fungus and leaf-blight bacterium in rice
Authors: Jiang Tingting , Huang Ning , Wang Zhixue , Li Jiawen , Ma Lu , Wang Xinying , Shen Lingtong , Zhang Ying , Yu Yao , Wang Wei , Fan Yunxin , Liu Kunquan , Zhao Zhi , Xiong Ziwei , Song Qisheng , Tang Haijuan , Zhang Hongsheng , Bao Yongmei
Published: August 2024

Amino acid transporters (AATs) have been shown to be involved in immune responses during plant–pathogen interactions; however, the molecular mechanism by which they function in this process remains unclear. Here, we used a joint analysis of a genome-wide association study and quantitative trait locus (QTL) mapping to identify MEMBRANE PROTEIN 1, which acts as a QTL in rice against blast fungus. Heterogeneous expression of OsMP1 in yeast supported its function in transporting a wide range of amino acids, including Thr, Ser, Phe, His, and Glu. OsMP1 could also mediate 15N-Glu efflux and influx in Xenopus oocyte cells. The expression of OsMP1 was significantly induced by Magnaporthe oryzae in the resistant rice landrace Heikezijing, whereas no such induction was observed in the susceptible landrace Suyunuo. Overexpressing OsMP1 in Suyunuo enhanced disease resistance to blast fungus and leaf blight bacterium without resulting in a yield penalty. In addition, the overexpression of OsMP1 led to increased accumulation of Thr, Ser, Phe, and His in the leaves and this contributed to the reduced disease susceptibility, which was associated with up-regulation of the jasmonic acid pathway. Our results demonstrate the important role of OsMP1 in disease resistance in rice and provide a potential target for breeding more resistant cultivars without reducing yield.
Prevalence of social frailty in patients with rheumatoid arthritis: Data from a multicentre observational study (T-FLAG study)
Authors: Suzuki Mochihito , Asai Shuji , Ohashi Yoshifumi , Sobue Yasumori , Ishikawa Hisato , Terabe Kenya , Sato Ryo , Kosugiyama Hironobu , Hasegawa Junya , Ohno Yusuke , Sugiura Takaya , Imagama Shiro
Published: August 2024

Objectives

The aim of this study was to investigate the prevalence of social frailty and associated factors.

Methods

A total of 655 consecutive patients who were able to complete the Kihon Checklist (KCL) and the Questionnaire on Social Frailty between June and August 2022 were enrolled. Social frailty was assessed using the Makizako Social Frailty Index. Patient characteristics were analysed by analysis of variance. Factors associated with social frailty were analysed using multivariate logistic analysis. Spearman’s rank correlation coefficients were used to examine correlations between each KCL domain and social frailty.

Results

The mean age was 68 years, and the disease duration was 12 years; 73% of patients were female. Social frailty was present in 30.8% of patients, with 36.5% classified as social prefrailty. Multivariate analysis revealed age and Health Assessment Questionnaire-Disability Index to be independent factors associated with social frailty. The proportion of social frailty increased with increasing age and worsening Health Assessment Questionnaire-Disability Index scores. The KCL domain ‘Isolation’ was the most strongly associated with social frailty (r = .601, P < .001), with higher scores associated with a higher proportion of social frailty.

Conclusions

Social frailty in patients with rheumatoid arthritis is associated with age and physical impairment (Health Assessment Questionnaire-Disability Index). Moreover, the KCL domain ‘Isolation’ was strongly associated with social frailty.
Advances in neural architecture search
Authors: Wang Xin , Zhu Wenwu
Published: August 2024

Automated machine learning (AutoML) has achieved remarkable success in automating the non-trivial process of designing machine learning models. Among the focal areas of AutoML, neural architecture search (NAS) stands out, aiming to systematically explore the complex architecture space to discover the optimal neural architecture configurations without intensive manual interventions. NAS has demonstrated its capability of dramatic performance improvement across a large number of real-world tasks. The core components in NAS methodologies normally include (i) defining the appropriate search space, (ii) designing the right search strategy and (iii) developing the effective evaluation mechanism. Although early NAS endeavors are characterized via groundbreaking architecture designs, the imposed exorbitant computational demands prompt a shift towards more efficient paradigms such as weight sharing and evaluation estimation, etc. Concurrently, the introduction of specialized benchmarks has paved the way for standardized comparisons of NAS techniques. Notably, the adaptability of NAS is evidenced by its capability of extending to diverse datasets, including graphs, tabular data and videos, etc., each of which requires a tailored configuration. This paper delves into the multifaceted aspects of NAS, elaborating on its recent advances, applications, tools, benchmarks and prospective research directions.
Thermal management with innovative fibers and textiles: manipulating heat transport, storage and conversion
Authors: Peng Yucan , Cui Yi
Published: August 2024

Thermal management is essential for maintaining optimal performance across various applications, including personal comfort, electronic systems and industrial processes. Thermal-management fibers and textiles have emerged as innovative solutions to manipulate heat transport, storage and conversion efficiently. This review explores recent advancements in material innovations in this field. We summarize the novel fibers and textiles designed for controlling heat transport through different pathways, progress in developing phase-change-material-based fibers and textiles for heat storage regulation, and application of photothermal conversion, Joule heating and thermoelectric effect as energy conversion routes in advanced fibers and textiles. Furthermore, we discuss the challenges and future perspectives of this field. It is believed that ongoing research and development promise to bring about innovative thermal-management solutions catering to demands across multiple sectors.
Tomonaga–Luttinger liquid and quantum criticality in spin-12 antiferromagnetic Heisenberg chain C14H18CuN4O10 via Wilson ratio
Authors: Channarayappa Sharath Kumar , Kumar Sankalp , Vidhyadhiraja N S , Pujari Sumiran , Saravanan M P , Sebastian Amal , Choi Eun Sang , Chikara Shalinee , Nambi Dolly , Suresh Athira , Lal Siddhartha , Jaiswal-Nagar D
Published: August 2024

The ground state of a one-dimensional spin-12 uniform antiferromagnetic Heisenberg chain (AfHc) is a Tomonaga–Luttinger liquid which is quantum-critical with respect to applied magnetic fields up to a saturation field μ0Hs beyond which it transforms to a fully polarized state. Wilson ratio has been predicted to be a good indicator for demarcating these phases [Phys. Rev. B 96, 220401 (2017)]. From detailed temperature and magnetic field-dependent magnetization, magnetic susceptibility and specific heat measurements in a metalorganic complex and comparisons with field theory and quantum transfer matrix method calculations, the complex was found to be a very good realization of a spin-12 AfHc. Wilson ratio obtained from experimentally obtained magnetic susceptibility and magnetic contribution of specific heat values was used to map the magnetic phase diagram of the uniform spin-12 AfHc over large regions of phase space demarcating Tomonaga–Luttinger liquid, saturation field quantum critical, and fully polarized states. Luttinger parameter and spinon velocity were found to match very well with the values predicted from conformal field theory.
Microvascular network based on the Hilbert curve for nutrient transport in thick tissue
Authors: Wang Zhenxing , Liu Xuemin , Shi Xuetao , Wang Yingjun
Published: August 2024

To address the uneven nutrient distribution within three-dimensional (3D) tissue models and organoids currently used in medical research, this study introduces a microvascular network based on the Hilbert curve. Our aim was to develop innovative solutions for enhancing nutrient supply in thick tissue models in vitro. By using 3D bioprinting, we engineered microvascular networks of varying Hilbert orders and validated their efficacy in enhancing nutrient uniformity through numerical simulations and experiments. These networks facilitated broader and more uniform nutrient distribution throughout the thick tissue models, particularly the 2° Hilbert microvascular structure, which occupies less space and significantly reduces regions of cellular death. Furthermore, we explored the potential of assembling larger tissue constructs using the 2° Hilbert microvascular network, showcasing its applicability in constructing large-scale biological models. The findings suggest that the 2° Hilbert microvascular structure is particularly effective in ensuring adequate nutrient delivery, thus enhancing the viability and functionality of large-volume tissue models. These innovations hold significant promise for advancing the fields of tissue engineering and regenerative medicine by improving nutrient delivery to in vitro thick tissue block models. This provides a robust foundation for future in vitro research and clinical applications, potentially leading to more effective treatments and interventions in the medical field. The development of these microvascular networks represents a crucial step forward in overcoming the limitations of current 3D tissue models and organoids, paving the way for more sophisticated and reliable biomedical research tools.
Calcium silicate cements endowing bioactivity and sustaining mechanical strength of low-heat-releasing and fast-curing magnesium phosphate cements
Authors: Xie Lijun , Zhang Yan , Cao Binji , Jiao Xiaoyi , Yue Xusong , Xu Yan , Yang Xianyan , Yang Guojing , Wang Yingjie , Shen Jian , Wang Cong , Weng Xisheng , Gou Zhongru
Published: August 2024

It is known that magnesium phosphate cements (MPCs) show appreciable mechanical strength and biocompatibility, but the hydration reaction processes often lead to intense heat release while the hydration products present weak resistance to mechanical decay and low bioactivity. Herein we developed an MPC-based system, which was low-heat-releasing and fast-curing in this study, by compounding with self-curing calcium silicate cements (CSCs). The MPC composed of magnesium oxide (MgO), potassium dihydrogen phosphate (KH2PO4), disodium hydrogen phosphate (Na2HPO4), magnesium hydrogen phosphate trihydrate (MgHPO4·3H2O) and chitosan were weakly basic, which would be more stable in vivo. The physicochemical properties indicated that the addition of CSCs could increase the final setting time while decrease the heat release. Meanwhile, the CSCs could endow MPC substrate with apatite re-mineralization reactivity, especially, which add 25 wt.% CSCs showed the most significant apatite deposition. What’s more, the mechanical evolution in buffer demonstrated CSCs could enhance and sustain the mechanical strength during degradation, and the internal constructs of cement implants could still be reconstructed by μCT analysis in rabbit femoral bone defect model in vivo. Particularly, appropriate CSCs adjusted the biodegradation and promoted new bone tissue regeneration in vivo. Totally, the MPC/CSCs composite system endows bioactivity and sustains mechanical strength of the MPC, which may be promising for expending the clinical applications of MPC-based bone cements.
A promising strategy for combating bacterial infections through the use of light-triggered ROS in Ce6-immobilized hydrogels
Authors: Hong Seung Hee , Lee Mi Hee , Go Eun Jeong , Park Jong-Chul
Published: August 2024

The reactive oxygen species (ROS) are composed of highly reactive molecules, including superoxide anions (O2•−), hydrogen peroxide (H2O2) and hydroxyl radicals. Researchers have explored the potential benefits of using hydrogel dressings that incorporate active substances to accelerate wound healing. The present investigation involved the development of a hyaluronic acid (HA) hydrogel capable of producing ROS using LED irradiation. The process of creating a composite hydrogel was created by chemically bonding Ce6 to an amide group. Our analysis revealed that the synthesized hydrogel had a well-structured amide bond, and the degree of cross-linking was assessed through swelling, enzyme stability and cytotoxicity tests. ROS production was found to be influenced by both the intensity and duration of light exposure. Furthermore, in situations where cell toxicity resulting from ROS generation in the hydrogel surpassed 70%, no detectable genotoxic consequences were evident, and antibacterial activity was confirmed to be directly caused by the destruction of bacterial membranes as a result of ROS damage. Furthermore, the utilization of the generated ROS influences the polarization of macrophages, resulting in the secretion of pro-inflammatory cytokines, which is a characteristic feature of M1 polarization. Subsequently, we validated the efficacy of a HA hydrogel that produces ROS to directly eradicate microorganisms. Furthermore, this hydrogel facilitated indirect antibacterial activity by stimulating macrophages to release pro-inflammatory cytokines. These cytokines are crucial for coordinating cell-mediated immune responses and for modulating the overall effectiveness of the immune system. Therefore, the Ce6-HA hydrogel has the potential to serve as an effective wound dressing solution for infected wounds because of its ability to produce substantial levels or a consistent supply.
Monitoring the sleep health of adults: a scoping review of routine national surveillance systems
Authors: Way Joshua A H , Ucak Seren , Martinez Chloe-Anne , Sutherland Kate , Cook Kristina M , Cistulli Peter A , Bin Yu Sun
Published: August 2024

Study Objectives

The aims of this review were to identify existing national surveillance systems monitoring one or more domains of sleep health in adults, and to describe the specific sleep health indicators used.

Methods

We systematically searched the gray and peer-reviewed literature for routinely conducted cross-sectional and longitudinal nationally representative health surveys that included the assessment of at least one domain of sleep health. The methodology involved: (1) targeted searches of the websites of national and international health agencies and statistics departments for 199 countries, (2) country-specific customized internet searches, and (3) country-specific electronic database searches of PubMed.

Results

A total of 19 762 records were identified from both the gray and peer-reviewed literature. Sleep health surveillance at the national level was conducted by 51 countries (25.6%) across 69 national health surveys. Sleep quality (96.1% of countries that surveilled sleep) was the most frequently assessed followed by sleep duration (27.5%), sleep medication use (25.5%), sleep disorders (17.6%), daytime alertness (15.7%), sleep satisfaction (15.7%), and sleep timing (7.8%). Additionally, 34.8% of the surveys utilized multiple sleep health indicators.

Conclusions

This study identified three significant gaps in the coverage of sleep health within national surveillance systems. Limited population sleep data in low- and middle-income countries, inconsistent use of sleep-related items in surveys and questionnaires, and substantial variability in the definitions of sleep health indicators. Advocacy for the inclusion of sleep health within national surveillance systems may be warranted given the important role sleep plays in public health.
Intra- and inter-subtype HIV diversity between 1994 and 2018 in southern Uganda: a longitudinal population-based study
Authors: Kim Seungwon , Kigozi Godfrey , Martin Michael A , Galiwango Ronald M , Quinn Thomas C , Redd Andrew D , Ssekubugu Robert , Bonsall David , Ssemwanga Deogratius , Rambaut Andrew , Herbeck Joshua T , Reynolds Steven J , Foley Brian , Abeler-Dörner Lucie , Fraser Christophe , Ratmann Oliver , Kagaayi Joseph , Laeyendecker Oliver , Grabowski Mary K
Published: August 2024

There is limited data on human immunodeficiency virus (HIV) evolutionary trends in African populations. We evaluated changes in HIV viral diversity and genetic divergence in southern Uganda over a 24-year period spanning the introduction and scale-up of HIV prevention and treatment programs using HIV sequence and survey data from the Rakai Community Cohort Study, an open longitudinal population-based HIV surveillance cohort. Gag (p24) and env (gp41) HIV data were generated from people living with HIV (PLHIV) in 31 inland semi-urban trading and agrarian communities (1994–2018) and four hyperendemic Lake Victoria fishing communities (2011–2018) under continuous surveillance. HIV subtype was assigned using the Recombination Identification Program with phylogenetic confirmation. Inter-subtype diversity was evaluated using the Shannon diversity index, and intra-subtype diversity with the nucleotide diversity and pairwise TN93 genetic distance. Genetic divergence was measured using root-to-tip distance and pairwise TN93 genetic distance analyses. Demographic history of HIV was inferred using a coalescent-based Bayesian Skygrid model. Evolutionary dynamics were assessed among demographic and behavioral population subgroups, including by migration status. 9931 HIV sequences were available from 4999 PLHIV, including 3060 and 1939 persons residing in inland and fishing communities, respectively. In inland communities, subtype A1 viruses proportionately increased from 14.3% in 1995 to 25.9% in 2017 (P < .001), while those of subtype D declined from 73.2% in 1995 to 28.2% in 2017 (P < .001). The proportion of viruses classified as recombinants significantly increased by nearly four-fold from 12.2% in 1995 to 44.8% in 2017. Inter-subtype HIV diversity has generally increased. While intra-subtype p24 genetic diversity and divergence leveled off after 2014, intra-subtype gp41 diversity, effective population size, and divergence increased through 2017. Intra- and inter-subtype viral diversity increased across all demographic and behavioral population subgroups, including among individuals with no recent migration history or extra-community sexual partners. This study provides insights into population-level HIV evolutionary dynamics following the scale-up of HIV prevention and treatment programs. Continued molecular surveillance may provide a better understanding of the dynamics driving population HIV evolution and yield important insights for epidemic control and vaccine development.