bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimalarial resistance risk in Mozambique detected by a novel quadruplex droplet digital PCR assay
Authors: Brown Noah , da Silva Clemente , Webb Caroline , Matias Daniela , Dias Brigite , Cancio Beatriz , Silva Miguel , Viegas Ruben , Salvador Crizolgo , Chivale Nordino , Luis Sonia , Arnaldo Paulo , Zulawinska Julia , Moore Christopher C. , Nogueira Fatima , Guler Jennifer L.
Published: May 2024

While the
Plasmodium falciparum
malaria parasite continues to cause severe disease globally, Mozambique is disproportionally represented in malaria case totals. Acquisition of copy number variations (CNVs) in the parasite genome contributes to antimalarial drug resistance through overexpression of drug targets. Of interest, piperaquine resistance is associated with plasmepsin 2 and 3 CNVs (
pfpmp2
and
pfpmp3,
respectively), while CNVs in the multidrug efflux pump, multidrug resistance-1 (
pfmdr1
), increase resistance to amodiaquine and lumefantrine. These antimalarials are partner drugs in artemisinin combination therapies (ACTs) and therefore, CNV detection with accurate and efficient tools is necessary to track ACT resistance risk. Here, we evaluated ~300 clinically derived samples collected from three sites in Mozambique for resistance-associated CNVs. We developed a novel, medium-throughput, quadruplex droplet digital PCR (ddPCR) assay to simultaneously quantify the copy number of
pfpmp3, pfpmp2
, and
pfmdr1
loci in these clinical samples. By using DNA from laboratory parasite lines, we show that this nanodroplet-based method is capable of detecting picogram levels of parasite DNA, which facilitates its application for low yield and human host-contaminated clinical surveillance samples. Following ddPCR and the application of quality control standards, we detected CNVs in 13 of 229 high-quality samples (prevalence of 5.7%). Overall, our study revealed a low number of resistance CNVs present in the parasite population across all three collection sites, including various combinations of
pfmdr1
,
pfpmp2
, and
pfpmp3
CNVs. The potential for future ACT resistance across Mozambique emphasizes the need for continued molecular surveillance across the region.
Plasma and tissue concentrations of 2 g prophylactic cefazolin prior to lower extremity surgery
Authors: Eelsing Robin , Penning Diederick , Vos-van der Meer Marloes , Hodiamont Caspar J. , Mathôt Ron A. A. , Schepers Tim
Published: May 2024

Surgical site infections (SSIs) are among the most clinically relevant complications and the use of prophylactic cefazolin is common practice. However, the knowledge about the pharmacological aspects of prophylactic cefazolin in the lower extremities remains limited. In this prospective cohort, a sub-study of the WIFI-2 randomized controlled trial, adults between 18 and 75 years of age who were scheduled for implant removal below the level of the knee and randomized for cefazolin, was included. A maximum of two venous plasma, target-site plasma, and target-site tissue samples were taken during surgery. The primary outcomes were the cefazolin concentrations in venous plasma, target-site plasma, and target-site tissue. A total of 27 patients [median (interquartile range) age, 42 (29–59) years; 17 (63%) male] with 138 samples were included in the study. A minimum of 6 weeks follow-up was available for all patients. The mean (SD) venous plasma, target-site plasma, and target-site tissue concentrations were 36 (13) µg/mL, 29 (13) µg/mL, and 28 (13) µg/g, respectively, and the cefazolin concentrations between the different locations of surgery did not differ significantly in both target-site plasma and target-site tissue (
P
= 0.822 and
P
= 0.840). In conclusion, 2 g of prophylactic cefazolin demonstrates adequacy in maintaining coverage for a duration of at least 80 minutes of surgery below the level of the knee, significantly surpassing the MIC
90
required to combat the most prevalent microorganisms. This study represents the first of its kind to assess cefazolin concentrations in the lower extremities by examining both plasma and tissue samples in this magnitude.
Soil fungal community has higher network stability than bacterial community in response to warming and nitrogen addition in a subtropical primary forest
Authors: Li Debao , Wu Chuansheng , Wu Jianping
Published: May 2024

Global change factors are known to strongly affect soil microbial community function and composition. However, as of yet, the effects of warming and increased anthropogenic nitrogen deposition on soil microbial network complexity and stability are still unclear. Here, we examined the effects of experimental warming (3°C above ambient soil temperature) and nitrogen addition (5 g N m
−2
year
−1
) on the complexity and stability of the soil microbial network in a subtropical primary forest. Compared to the control, warming increased |negative cohesion|:positive cohesion by 7% and decreased network vulnerability by 5%; nitrogen addition decreased |negative cohesion|:positive cohesion by 10% and increased network vulnerability by 11%. Warming and decreased soil moisture acted as strong filtering factors that led to higher bacterial network stability. Nitrogen addition reduced bacterial network stability by inhibiting soil respiration and increasing resource availability. Neither warming nor nitrogen addition changed fungal network complexity and stability. These findings suggest that the fungal community is more tolerant than the bacterial community to climate warming and nitrogen addition. The link between bacterial network stability and microbial community functional potential was significantly impacted by nitrogen addition and warming, while the response of soil microbial network stability to climate warming and nitrogen deposition may be independent of its complexity. Our findings demonstrate that changes in microbial network structure are crucial to ecosystem management and to predict the ecological consequences of global change in the future.

IMPORTANCE

Soil microbes play a very important role in maintaining the function and health of forest ecosystems. Unfortunately, global change factors are profoundly affecting soil microbial structure and function. In this study, we found that climate warming promoted bacterial network stability and nitrogen deposition decreased bacterial network stability. Changes in bacterial network stability had strong effects on bacterial community functional potentials linked to metabolism, nitrogen cycling, and carbon cycling, which would change the biogeochemical cycle in primary forests.
Critical analysis of polycyclic tetramate macrolactam biosynthetic gene cluster phylogeny and functional diversity
Authors: Harper Christopher P. , Day Anna , Tsingos Maya , Ding Edward , Zeng Elizabeth , Stumpf Spencer D. , Qi Yunci , Robinson Adam , Greif Jennifer , Blodgett Joshua A. V.
Published: May 2024

Polycyclic tetramate macrolactams (PTMs) are bioactive natural products commonly associated with certain actinobacterial and proteobacterial lineages. These molecules have been the subject of numerous structure-activity investigations since the 1970s. New members continue to be pursued in wild and engineered bacterial strains, and advances in PTM biosynthesis suggest their outwardly simplistic biosynthetic gene clusters (BGCs) belie unexpected product complexity. To address the origins of this complexity and understand its influence on PTM discovery, we engaged in a combination of bioinformatics to systematically classify PTM BGCs and PTM-targeted metabolomics to compare the products of select BGC types. By comparing groups of producers and BGC mutants, we exposed knowledge gaps that complicate bioinformatics-driven product predictions. In sum, we provide new insights into the evolution of PTM BGCs while systematically accounting for the PTMs discovered thus far. The combined computational and metabologenomic findings presented here should prove useful for guiding future discovery.

IMPORTANCE

Polycyclic tetramate macrolactam (PTM) pathways are frequently found within the genomes of biotechnologically important bacteria, including
Streptomyces
and
Lysobacter
spp
.
Their molecular products are typically bioactive, having substantial agricultural and therapeutic interest. Leveraging bacterial genomics for the discovery of new related molecules is thus desirable, but drawing accurate structural predictions from bioinformatics alone remains challenging. This difficulty stems from a combination of previously underappreciated biosynthetic complexity and remaining knowledge gaps, compounded by a stream of yet-uncharacterized PTM biosynthetic loci gleaned from recently sequenced bacterial genomes. We engaged in the following study to create a useful framework for cataloging historic PTM clusters, identifying new cluster variations, and tracing evolutionary paths for these molecules. Our data suggest new PTM chemistry remains discoverable in nature. However, our metabolomic and mutational analyses emphasize the practical limitations of genomics-based discovery by exposing hidden complexity.
COVID-19 therapeutics
Authors: Focosi Daniele , Franchini Massimo , Maggi Fabrizio , Shoham Shmuel
Published: May 2024

Since the emergence of COVID-19 in 2020, an unprecedented range of therapeutic options has been studied and deployed. Healthcare providers have multiple treatment approaches to choose from, but efficacy of those approaches often remains controversial or compromised by viral evolution. Uncertainties still persist regarding the best therapies for high-risk patients, and the drug pipeline is suffering fatigue and shortage of funding. In this article, we review the antiviral activity, mechanism of action, pharmacokinetics, and safety of COVID-19 antiviral therapies. Additionally, we summarize the evidence from randomized controlled trials on efficacy and safety of the various COVID-19 antivirals and discuss unmet needs which should be addressed.
Lipid A modification of colistin-resistant
Klebsiella pneumoniae
does not alter innate immune response in a mouse model of pneumonia
Authors: Bhushan Gitanjali , Castano Victor , Wong Fok Lung Tania , Chandler Courtney , McConville Thomas H. , Ernst Robert K. , Prince Alice S. , Ahn Danielle
Published: May 2024

Polymyxin resistance in carbapenem-resistant
Klebsiella pneumoniae
bacteria is associated with high morbidity and mortality in vulnerable populations throughout the world. Ineffective antimicrobial activity by these last resort therapeutics can occur by transfer of
mcr-1
, a plasmid-mediated resistance gene, causing modification of the lipid A portion of lipopolysaccharide (LPS) and disruption of the interactions between polymyxins and lipid A. Whether this modification alters the innate host immune response or carries a high fitness cost in the bacteria is not well established. To investigate this, we studied infection with
K. pneumoniae
(KP) ATCC 13883 harboring either the
mcr-1
plasmid (p
mcr-1
) or the vector control (pBCSK) ATCC 13883. Bacterial fitness characteristics of
mcr-1
acquisition were evaluated. Differentiated human monocytes (THP-1s) were stimulated with KP bacterial strains or purified LPS from both parent isolates and isolates harboring
mcr-1
. Cell culture supernatants were analyzed for cytokine production. A bacterial pneumonia model in WT C57/BL6J mice was used to monitor immune cell recruitment, cytokine induction, and bacterial clearance in the bronchoalveolar lavage fluid (BALF). Isolates harboring
mcr-1
had increased colistin MIC compared to the parent isolates but did not alter bacterial fitness. Few differences in cytokines were observed with purified LPS from
mcr-1
expressing bacteria
in vitro
. However, in a mouse pneumonia model, no bacterial clearance defect was observed between p
mcr-1
-harboring KP and parent isolates. Consistently, no differences in cytokine production or immune cell recruitment in the BALF were observed, suggesting that other mechanisms outweigh the effect of these lipid A mutations in LPS.
Final closure of the Paleo-Tethys Ocean: Insights from Triassic granitoids in the central Qiangtang area, northern Tibetan Plateau
Authors: Zhai Qingguo , Hu Peiyuan , Liu Yiming , Tang Yue , Lee Haoyang
Published: May 2024

The geodynamic evolution during the closure of the Paleo-Tethys Ocean in the Tibetan Plateau remains to be fully understood. The Longmu Co–Shuanghu suture zone in the northern Tibetan Plateau has usually been considered to represent the main ocean basin of the Paleo-Tethys Ocean, so it plays a key role in understanding the evolution of the Paleo-Tethys Ocean. In this study, we focused on the Gacuo and Bensong batholiths on the north and south sides of the Longmu Co–Shuanghu suture zone, respectively. We conducted detailed zircon geochronology and whole-rock geochemical and Sr-Nd isotopic analyses, as well as zircon Hf isotope studies. Zircon U-Pb dating indicates that the Gacuo batholith was formed ca. 223–209 Ma, and the age of the Bensong batholith is ca. 213–203 Ma. The Gacuo batholith is mainly composed of I-type granitoids, which are most likely attributed to partial melting of ancient sedimentary materials of the North Qiangtang terrane with a mixture of ~0%–30% amounts of mantle-derived components. In contrast, the Bensong batholith has granitoids of A-type affinity, and it was probably generated by partial melting of Mesoproterozoic crust of the South Qiangtang terrane with limited mantle contribution (<5%). Finally, we suggest that the Gacuo batholith was probably generated by the break-off of the oceanic slab beneath the North Qiangtang terrane, while the Bensong batholith was related to a possible lithospheric delamination process of the South Qiangtang terrane after continental collision. Therefore, the Gacuo and Bensong batholiths both developed in a postcollisional tectonic setting, and they recorded the evolutionary process of the subduction and closure of the Paleo-Tethys Ocean during the Late Triassic.
Stakeholder perspectives on contributors to delayed and inaccurate diagnosis of cardiovascular disease and their implications for digital health technologies: a UK-based qualitative study
Authors: Abdullayev Kamilla , Gorvett Olivia , Sochiera Anna , Laidlaw Lynn , Chico Timothy , Manktelow Matthew , Buckley Oliver , Condell Joan , Van Arkel Richard , Diaz Vanessa , Matcham Faith
Published: May 2024

Objective

The aim of this study is to understand stakeholder experiences of diagnosis of cardiovascular disease (CVD) to support the development of technological solutions that meet current needs. Specifically, we aimed to identify challenges in the process of diagnosing CVD, to identify discrepancies between patient and clinician experiences of CVD diagnosis, and to identify the requirements of future health technology solutions intended to improve CVD diagnosis.

Design

Semistructured focus groups and one-to-one interviews to generate qualitative data that were subjected to thematic analysis.

Participants

UK-based individuals (N=32) with lived experience of diagnosis of CVD (n=23) and clinicians with experience in diagnosing CVD (n=9).

Results

We identified four key themes related to delayed or inaccurate diagnosis of CVD: symptom interpretation, patient characteristics, patient–clinician interactions and systemic challenges. Subthemes from each are discussed in depth. Challenges related to time and communication were greatest for both stakeholder groups; however, there were differences in other areas, for example, patient experiences highlighted difficulties with the psychological aspects of diagnosis and interpreting ambiguous symptoms, while clinicians emphasised the role of individual patient differences and the lack of rapport in contributing to delays or inaccurate diagnosis.

Conclusions

Our findings highlight key considerations when developing digital technologies that seek to improve the efficiency and accuracy of diagnosis of CVD.
Characteristics of first-time users of the nursing small-scale multifunctional home care service: a pooled cross-sectional study using Japanese long-term care insurance claims data from 2012 to 2019
Authors: Morioka Noriko , Kashiwagi Masayo , Kashiwagi Kimikazu , Abe Kazuhiro , Miyawaki Atsushi
Published: May 2024

Objectives

In April 2012, the Japanese government launched a new nursing service called the nursing small-scale multifunctional home care (NSMHC) to meet the nursing care demands of individuals with moderate-to-severe activities of daily living (ADLs) dysfunction and who require medical care, thereby allowing them to continue living in the community. We aimed to preliminarily analyse the characteristics of first-time users of NSMHC service.

Design

This pooled cross-sectional study used the Japanese long-term care insurance (LTCI) claims data from the users’ first use of NSMHC (from April 2012 to December 2019).

Setting

NSMHC includes nursing home visits, home care, daycare, overnight stays and medical treatment.

Participants

The study population included LTCI beneficiaries who received their first long-term care requirement certification in Japan from April 2012 onwards, died between April 2012 and December 2019, and used any LTCI service at least once.

Results

Among the 836 563 individuals who used any LTCI service at least once, 3957 (0.47%) used NSMHC. We analysed 3634 individuals without any missing data regarding long-term care requirement certification. Most individuals were aged 80 years or older, with 64.3% requiring care level 3 or above, indicating complete assistance with ADLs. Regarding ADLs in individuals with dementia, 70.6% were at level 2 or below, indicating they can live almost independently even with dementia. A large proportion of NSMHC users availed the service approximately 6 months before death, with no prior use of any LTCI services; they continued using the service for around 4 months, although some people continued to use NSMHC until their month of death.

Conclusions

Using individual data on nationwide LTCI, we described the characteristics of first-time users of NSMHC among those who died within 7.5 years from the first certification of care needs. Further studies are needed to investigate the effect of NSMHC use on user outcomes.
Does living alone influence fall risk among Swiss older adults aged 60+? A pooled observational analysis of three RCTs on fall prevention
Authors: Braendle Kilian , Egli Andreas , Bischoff-Ferrari Heike , Freystaetter Gregor
Published: May 2024

Objectives

Falling and living alone have been identified as public health challenges in an ageing society. Our study investigates whether living alone influences fall risk in community-dwelling older adults in Switzerland.

Design and methods

Secondary analysis of three randomised controlled trials investigating how different doses of vitamin D and an exercise programme may influence the risk of further falls in people 60+ at risk of falling. We used logistic regression to examine the association between living alone and the odds of becoming a faller, and negative binomial regression to examine the association between living alone and the rate of falls. We assessed both any falls and falls with injury. All analyses were adjusted for sex, body mass index, age, grip strength, comorbidities, use of walking aids, mental health, trial and treatment group. Predefined subgroups were by sex and age.

Results

Among 494 participants (63% women; mean age was 74.7±7.5 years) 643 falls were recorded over 936.5 person-years, including 402 injurious falls. Living alone was associated with a 1.76-fold higher odds of becoming a faller (OR (95% CI)=1.76 (1.11 to 2.79)). While the odds did not differ by sex, older age above the median age of 74.6 years increased the odds to 2.19-fold (OR (95% CI)=2.19 (1.11 to 4.32)). The rate of total or injurious falls did not differ by living status.

Conclusions

Community-dwelling older adults living alone have a higher odds of becoming a faller. The increased odds is similar for men and women but accentuated with higher age.

Trial registration numbers

ZDPT:NCT01017354, NFP53:NCT00133640, OA:NCT00599807.
Effect of HIV and substance use disorder comorbidity on the placenta, fetal and maternal health outcomes: systematic review and meta-analysis protocol
Authors: Sorato Mende Mensa , Alemu Tsegaye , Toma Alemayehu , Paulos Getahun , Mekonnen Shewangizaw
Published: May 2024

Background

Substance use disorders and HIV infection have a bidirectional relationship. People who use illicit drugs are at increased risk of contracting HIV/AIDS, and people living with HIV/AIDS are at increased risk of using substances due to disease-related complications like depression and HIV-associated dementia. There is no adequate evidence on the effect of HIV/AIDS and substance use disorder comorbidity-related effects on placental, fetal, maternal and neonatal outcomes globally.

Methods and analysis

We will search articles written in the English language until 30 January 2024, from PubMed/Medline, Cochrane Library, Embase, Scopus, Web of Sciences, SUMsearch2, Turning Research Into Practice database and Google Scholar. A systematic search strategy involving AND/OR Boolean Operators will retrieve information from these databases and search engines. Qualitative and quantitative analysis methods will be used to report the effect of HIV/AIDS and substance use disorders on placental, fetal and maternal composite outcomes. Descriptive statistics like pooled prevalence mean and SD will be used for qualitative analysis. However, quantitative analysis outcomes will be done by using Comprehensive Meta-Analysis Software for studies that are combinable. The individual study effects and the weighted mean difference will be reported in a forest plot. In addition to this, the presence of multiple morbidities like diabetes, chronic kidney disease and maternal haemoglobin level could affect placental growth, fetal growth and development, abortion, stillbirth, HIV transmission and composite maternal outcomes. Therefore, subgroup analysis will be done for pregnant women with multiple morbidities.

Ethics and dissemination

Since systematic review and meta-analysis will be conducted by using published literature, ethical approval is not required. The results will be presented in conferences and published in peer-reviewed journals.

PROSPERO registration number

CRD42023478360.
Cancer odds among Ohio firefighters: data from the Ohio Cancer Incidence Surveillance System (OCISS) 1996–2019
Authors: Olivo-Marston Susan Elizabeth , Singh Shashank , Hood Robert , Adetona Olorunfemi
Published: May 2024

Objectives

The objective of the current case–control study was to examine the odds of cancer among firefighters in the state of Ohio and compare the odds of being a firefighter versus police or the general population across different cancer types.

Methods

Cancer cases were examined from the Ohio Cancer Incidence Surveillance System (OCISS) between 1996 and 2019. Occupation status was classified as firefighter, police or general population. Logistic regression models were run to calculate ORs to determine the odds of being a firefighter compared with police or the general population across different cancer types. Models were adjusted for gender, race, age at cancer diagnosis and year of cancer diagnosis.

Results

Among the 906 164 cancer cases, 3397 were firefighters and 3341 were police. Firefighters were more likely to be men, white, non-Hispanic, married and a mean age of 66 at the time of cancer diagnosis. Firefighters had increased odds of cancer of the brain (OR=1.40, 95% CI: 0.99 to 1.99) and thyroid (OR=1.53, 95% CI: 1.05 to 2.23) compared with police and oesophageal (OR=1.83, 95% CI: 1.43 to 2.33), skin (OR=1.23, 95% CI: 1.06 to 1.42), brain (OR=1.37, 95% CI: 1.08 to 1.73) and thyroid (OR=1.52, 95% CI: 1.18 to 1.96) compared with the general population. They had decreased odds of pancreas, lung and bronchus and bladder compared with both police and the general population. Similar patterns were observed among male firefighters.

Conclusions

The current study demonstrated increased odds of several different types of cancer among Ohio firefighters compared with other individuals within the OCISS, which may be associated with differences in risk factors, including occupational exposures. The results align with evidence that firefighting is a cancer risk factor. This study is strengthened by the ability to also compare firefighters to police with regards to the odds of cancer. This supports future hypothesis-driven studies examining how specific occupational exposures are associated with increased cancer risk among Ohio firefighters.
Innovative continuum of care to promote exclusive breast feeding in Pakistan: protocol of a pilot randomised controlled trial
Authors: Chaudry Zahid Azam , Naz Tehmina , Arshad Iqra , Zahoor Aisha , Javaid Mahum , Sikander Siham
Published: May 2024

Background

Breastmilk being the ideal nutrition from birth to 2 years and beyond has many health benefits for both newborn and mothers. This study will assess the feasibility and acceptability of a continuum of care programme, which is a health facility and community based till 6 months post partum to encourage ideal breastfeeding practices.

Methods and analysis

A pilot randomised control trial having two-parallel arms of intervention and control groups was conducted in gynaecology and obstetrics department of Aziz Bhatti Shaheed Teaching Hospital with a community outreach component of 6 months. 50 women between 28 and 32 weeks of gestation fulfilling inclusion criteria will be allocated in 1:1 randomly into intervention and control groups through computer-generated random number generator software. 25 participants in intervention group will receive counselling and training on breast feeding during antenatal visits along with a family member of support by a trained female doctor within the hospital, at birth by a trained nurse and at home for 6 months by a trained lady health worker. It will be supported by reading materials and videos through a mobile phone WhatsApp application. The 25 participants in control group will receive the support already provided within the hospital and at home. The primary outcomes feasibility and acceptability will be determined at 6 months post partum from participants and providers by a semistructured questionnaire. The secondary outcomes are rates of infant early initiation and exclusive breast feeding at 2 weeks, 1, 3 and 6 months, Infant Feeding Attitude at 1 month and Breastfeeding Self-Efficacy at 3 months. Quantitative and qualitative data will be analysed via SPSS software V.20 and thematic analysis, respectively.

Conclusion

This pilot randomised controlled trial (RCT) will guide the interventions for the definite RCT.

Ethics and dissemination

Approved by institutional ethical committee, informed consent from all participants and results will be disseminated in peer-reviewed journal.

Trial registration number

NCT05951868.
Development and validation of a risk scoring system to identify patients with lupus nephritis in electronic health record data
Authors: Izadi Zara , Gianfrancesco Milena , Anastasiou Christine , Schmajuk Gabriela , Yazdany Jinoos
Published: May 2024

Objective

Accurate identification of lupus nephritis (LN) cases is essential for patient management, research and public health initiatives. However, LN diagnosis codes in electronic health records (EHRs) are underused, hindering efficient identification. We investigated the current performance of International Classification of Diseases (ICD) codes, 9th and 10th editions (ICD9/10), for identifying prevalent LN, and developed scoring systems to increase identification of LN that are adaptable to settings with and without LN ICD codes.

Methods

Training and test sets derived from EHR data from a large health system. An external set comprised data from the EHR of a second large health system. Adults with ICD9/10 codes for SLE were included. LN cases were ascertained through manual chart reviews conducted by rheumatologists. Two definitions of LN were used: strict (definite LN) and inclusive (definite, potential or diagnostic uncertainty). Gradient boosting models including structured EHR fields were used for predictor selection. Two logistic regression-based scoring systems were developed (‘LN-Code’ included LN ICD codes and ‘LN-No Code’ did not), calibrated and validated using standard performance metrics.

Results

A total of 4152 patients from University of California San Francisco Medical Center and 370 patients from Zuckerberg San Francisco General Hospital and Trauma Center met the eligibility criteria. Mean age was 50 years, 87% were female. LN diagnosis codes demonstrated low sensitivity (43–73%) but high specificity (92–97%). LN-Code achieved an area under the curve (AUC) of 0.93 and a sensitivity of 0.88 for identifying LN using the inclusive definition. LN-No Code reached an AUC of 0.91 and a sensitivity of 0.95 (0.97 for the strict definition). Both scoring systems had good external validity, calibration and performance across racial and ethnic groups.

Conclusions

This study quantified the underutilisation of LN diagnosis codes in EHRs and introduced two adaptable scoring systems to enhance LN identification. Further validation in diverse healthcare settings is essential to ensure their broader applicability.
Untangling the relationship between smoking and systemic sclerosis: an analysis of the EUSTAR cohort
Authors: Ciaffi Jacopo , Liem Sophie I E , Cannegieter Suzanne , Ahmed Saad , Hoekstra Eva M , Wiland Piotr , Atsumi Tatsuya , Szücs Gabriella , Balbir Gurman Alexandra , Czirják László , Zanatta Elisabetta , Koetter Ina , Henes Joerg C , Matucci-Cerinic Marco , Airò Paolo , Ursini Francesco , Huizinga Tom W J , De Vries-Bouwstra Jeska , Collaborators EUSTAR
Published: May 2024

Objectives

To untangle the association between smoking and systemic sclerosis (SSc).

Methods

In the European Scleroderma Trials and Research cohort, the autoantibody status was compared between ever-smokers and never-smokers. Time until disease progression was assessed using Kaplan-Meier curves. Cox models were built to investigate the influence of smoking over 15 years of follow-up. All analyses were performed for the total cohort and stratified for sex and for positivity of anti-centromere (ACA) and anti-topoisomerase antibodies (ATA).

Results

Overall, 12 314 patients were included in the study. Of these, 10 393 were women (84%), 4637 were ACA-positive (38%), 3919 were ATA-positive (32%) and 4271 (35%) were ever-smokers. In men, but not in women, smoking was associated with mortality (HR 1.63, 95% CI 1.23 to 2.16, p=0.001). Ever-smoking women were at higher risk for skin progression (HR 1.10, 95% CI 1.00 to 1.22, p=0.046) and for ‘any organ progression’ (HR 1.07, 95% CI 1.00 to 1.13, p=0.036). In women, 34% of never-smokers were ATA-positive compared with 21% of ever-smokers (p<0.001). In the group of ever-smokers, higher exposure rates, reflected by the number of pack-years (OR 0.98, 95% CI 0.97 to 0.99, p<0.001) and by smoking duration (OR 0.96, 95% CI 0.95 to 0.97, p<0.001), were associated with lower frequency of ATA. In ACA-positive patients, the risk of mortality (HR 1.29, 95% CI 1.02 to 1.63, p=0.033), cardiac involvement (HR 1.25, 95% CI 1.03 to 1.43, p=0.001), skin progression (HR 1.21, 95% CI 1.03 to 1.42, p=0.018) and ‘any organ progression’ (HR 1.14, 95% CI 1.05 to 1.24, p=0.002) was increased among smokers. In ATA-positive smoking patients, mortality (HR 1.40, 95% CI 1.10 to 1.78, p=0.006), skin progression (HR 1.19, 95% CI 1.03 to 1.37, p=0.020) digital ulcers (HR 1.17, 95% CI 1.02 to 1.34, p=0.029) and ‘any organ progression’ (HR 1.11, 95% CI 1.00 to 1.22, p=0.048) occurred more frequently.

Conclusions

Our stratified analysis demonstrates that smoking is associated with an increased risk for mortality in male SSc patients but not in women. Strikingly, smoking is associated with lower prevalence of ATA positivity, in particular in women. In both ATA-positive and ACA-positive patients, smoking is a risk factor for mortality, skin progression and ‘any organ progression’.
Machine learning identifies risk factors associated with long-term opioid use in fibromyalgia patients newly initiated on an opioid
Authors: Ramírez Medina Carlos Raúl , Feng Mengyu , Huang Yun-Ting , Jenkins David A , Jani Meghna
Published: May 2024

Objectives

Fibromyalgia is frequently treated with opioids due to limited therapeutic options. Long-term opioid use is associated with several adverse outcomes. Identifying factors associated with long-term opioid use is the first step in developing targeted interventions. The aim of this study was to evaluate risk factors in fibromyalgia patients newly initiated on opioids using machine learning.

Methods

A retrospective cohort study was conducted using a nationally representative primary care dataset from the UK, from the Clinical Research Practice Datalink. Fibromyalgia patients without prior cancer who were new opioid users were included. Logistic regression, a random forest model and Boruta feature selection were used to identify risk factors related to long-term opioid use. Adjusted ORs (aORs) and feature importance scores were calculated to gauge the strength of these associations.

Results

In this study, 28 552 fibromyalgia patients initiating opioids were identified of which 7369 patients (26%) had long-term opioid use. High initial opioid dose (aOR: 31.96, mean decrease accuracy (MDA) 135), history of self-harm (aOR: 2.01, MDA 44), obesity (aOR: 2.43, MDA 36), high deprivation (aOR: 2.00, MDA 31) and substance use disorder (aOR: 2.08, MDA 25) were the factors most strongly associated with long-term use.

Conclusions

High dose of initial opioid prescription, a history of self-harm, obesity, high deprivation, substance use disorder and age were associated with long-term opioid use. This study underscores the importance of recognising these individual risk factors in fibromyalgia patients to better navigate the complexities of opioid use and facilitate patient-centred care.
Seismic performance assessment of conventional construction and ductile concrete moment frames using performance-based unified procedure
Authors: Dolati Abouzar , Fazileh Farrokh , Fathi-Fazl Reza , Saatcioglu Murat , Huang Xu , Sayed Mohamed A.
Published: May 2024

A performance-based unified (PBU) procedure has recently been proposed by the National Research Council Canada to systematically evaluate seismic design requirements available in the National Building Code of Canada (NBC). Conventional construction reinforced concrete moment-resisting frame (CC-CMF) and ductile reinforced concrete moment-resisting frame (D-CMF) systems were used in this paper to first assess the proposed PBU procedure and second determine the adequacy of the basis for seismic design requirements in NBC and see its performance margin against different structural performance levels. Results indicate that the detailed screening in the PBU procedure efficiently reduces the number of incremental dynamic analysis by more than 60% for CC-CMF while providing remarkable accuracy. It was also found that the CC-CMF system designed for the Normal importance category can provide an adequate margin against life safety performance level objectives, while the D-CMF system designed for the same importance category passes the collapse prevention performance level criteria.
Prescribed fire effects on understory woody plants and fuels in Quercus–Pinus mixedwoods
Authors: Howie Noah A. , Goode J. Davis , Hart Justin L. , Dey Daniel C.
Published: May 2024

To enhance forest resilience to predicted increases in forest stressors, managers increasingly desire ecologically based restoration approaches that increase ecosystem adaptation potential. Mixedwood stands, which contain a range of life history and functional traits, may be more resistant and resilient to ecosystem stressors. Management of Quercus–Pinus mixedwood stands includes the use of prescribed fire, which requires an understanding of vegetation-fuels-fire feedbacks in these ecosystems. However, a paucity of knowledge exists on the intra-stand spatial patterns of fire effects. We analyzed the effects of a newly initiated prescribed fire program on the intra-stand characteristics of understory woody plants and fuelbed composition and loading in a long-unburned Quercus –Pinus mixedwood stand in Tennessee, USA. We sampled vegetation and fuels in two plots, one that experienced two prescribed fires (burned plot), and one fire-excluded plot directly adjacent (unburned plot). On the burned plot, we recorded lower sapling and seedling densities across taxa. Spatial analysis of advance reproduction in the burned plot indicated a combination of patchy fire effects, canopy openings, and high-light understory environments. We documented significant reductions in total fuel mass. The combination of spatial analysis and ordination revealed that prescribed fires homogenized fuel loads within the burned plot.
Analyzing cutting force and vibration amplitude in high-speed milling of SKD11 steel with thermal assistance
Authors: Luyen The-Thanh , Mac Thi-Bich , Nguyen Duc-Toan
Published: May 2024

In the realm of machining, the optimization of cutting conditions stands as a paramount pursuit for enhancing both efficiency and precision. This study embarks on a pioneering investigation delving into the intricate interplay among workpiece temperature, Thermal-Assisted High-Speed Machining (TA-HSM), cutting force dynamics, and vibration amplitudes during the milling process of SKD11 steel. Beyond a mere exploration, this research endeavors to unveil not only the impact of temperature and velocity on machining dynamics but also to delineate regions characterized by elevated temperature and velocity that exhibit the potential to mitigate cutting forces and vibrations, thereby refining machining methodologies. Experimental inquiries encompassing diverse temperature regimes, coupled with variations in cutting speeds, offer valuable insights into the nexus among temperature, cutting force and vibration amplitude. Of particular significance are the high-speed milling trials conducted under the most elevated admissible support temperature, which furnish elucidation on the ramifications of high speeds on cutting forces and vibrations. This inquiry constitutes a substantive contribution to the field by elucidating the correlation between cutting force and vibration amplitude under the thermal influence and high-speed milling within thermally demanding environments. Moreover, this study extends practical utility by proffering actionable insights into the optimal temperature range and cutting speeds requisite for effecting desired enhancements in machining productivity. By discerning and delineating these optimal parameters, this research endeavors to furnish tangible guidelines for practitioners seeking to optimize their machining processes, thus fostering advancements in both efficiency and precision within the machining domain.
Investigations of the growth and physical characteristics of ZNF2-DOPED GA2O3 thin films
Authors: Wei Sufen , Kao Chia-Yang , Su Zhi-Ting , Tsao En-Chi , Chen Guo-Syun , Yang Cheng-Fu , Chang Jui-Yang
Published: May 2024

This study began by preparing gallium oxide (Ga2O3) doped with zinc fluoride (ZnF2) and manufacturing a target material. Subsequently, electron beam (e-beam) deposition was employed to coat silicon substrates with the prepared material. Different heat treatment conditions were applied to the deposited films, followed by material and electrical property analyses. The investigation explored the impact of pre-sintering Ga2O3 at 950°C to transform it into a more stable [Formula: see text]-phase. For comparative purposes, some samples underwent annealing at 600°C in a nitrogen–hydrogen (95% N[Formula: see text] H2, abbreviated as N[Formula: see text]) mixed gas, which was used as a reduction atmosphere, to increase oxygen vacancies in the ZnF2-doped Ga2O3 thin films and consequently enhance their conductivity. The deposited ZnF2-doped Ga2O3 thin films initially exhibited an amorphous phase, with diffraction peaks appearing only after a 600°C annealing process. Pre-sintering Ga2O3 powder at 950°C promoted the emergence of the [Formula: see text]-phase, and the bandgap value increased after annealing. Measurements using B1500A revealed that sintering and annealing ZnF2-doped Ga2O3 thin films were essential steps to enhance their conductivity. X-ray photoelectron spectroscopy (XPS) further confirmed a significant correlation between the conductivity variation and the concentration of oxygen vacancies. Additionally, it was observed that the use of an N[Formula: see text] mixed gas further increased the presence of oxygen vacancies in the films. The results of this study provide an important method to make Ga2O3 thin films with conductivity, which can be utilized in the fabrication of Ga2O3 thin-film-based semiconductor devices in the future.
Enhancing grid stability through predictive control and fuzzy neural networks in flywheel energy storage systems integration
Authors: Lai Hoa Thi Thanh , Trung Hai Do , Lai K. L. , Nguyen Duc-Toan
Published: May 2024

Renewable energy systems, exemplified by solar and wind power, are increasingly integrated into modern power grids to mitigate environmental impact and reduce reliance on fossil fuels. However, the inherent intermittency and unpredictability of renewable energy sources pose challenges to grid stability and reliability. Energy Storage Systems (ESS) offer a promising solution to address these challenges by smoothing out power fluctuations and ensuring a consistent power supply. Among various ESS technologies, Flywheel Energy Storage Systems (FESS) have emerged as a noteworthy contender due to their rapid response times, low operating costs, and extended lifespan. This paper focuses on investigating the operation of a novel unit comprising a solar power system integrated with a Flywheel Energy Storage System (PV-FESS). The aim is to develop an effective control algorithm utilizing adaptive fuzzy neural networks and model predictive control (ANFIS-MPC) to manage power fluctuations stemming from renewable energy sources within the grid. The proposed control strategy aims to optimize the operation of the PV-FESS system by dynamically adjusting the energy absorption or release of the flywheel to maintain grid stability. Simulation studies conducted using Matlab-Simulink/Simcape software validate the efficacy of the ANFIS-MPC algorithm in mitigating abnormal fluctuations from renewable energy sources. The results demonstrate that the PV-FESS system effectively balances power fluctuations, ensuring a stable and reliable power output to the grid.
Enhancing EDM performance with multi-objective decision-making using copper-coated aluminum electrodes and TOPSIS methodology for Ti-6Al-4V machining
Authors: Hoang Vuong Pham , Huu Phan Nguyen , Shirguppikar Shailesh , Duc Toan Nguyen
Published: May 2024

The exploration of Electrical Discharge Machining (EDM) with coated electrodes represents a relatively novel research avenue, thereby yielding limited published research outcomes. The choice of coating material plays a pivotal role in the EDM machining process, and alterations in coating materials can directly influence the adjustment of technological parameters in EDM. Consequently, research dedicated to optimizing these technological parameters for EDM employing coated electrodes is of paramount importance, and it promises to advance the practical implementation of this cutting-edge technique. In this study, we systematically investigate the technological parameters for EDM employing a copper-coated aluminum electrode in the context of Ti-6Al-4V machining. Our research outcomes are framed within a multi-objective optimization paradigm, with a focus on Material Removal Rate (MRR) and Surface Roughness (SR) as vital quality indicators. To address the intricate multi-objective optimization challenge, we have harnessed the combined power of the Taguchi methodology and the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). The amalgamation of these techniques enables us to navigate the complexities of EDM parameter optimization effectively. Our findings reveal that the most favorable process parameters entail a configuration of [Formula: see text][Formula: see text]V, [Formula: see text] A, [Formula: see text][Formula: see text][Formula: see text]s, resulting in an MRR of 0.028[Formula: see text]mg/min and an SR of 7.56[Formula: see text][Formula: see text]m. These optimized parameters exemplify a substantial enhancement in machining efficiency and surface quality when utilizing coated electrodes. Moreover, our study scrutinizes the quality of the machined surface under optimal conditions with coated electrodes. We employ the TOPSIS method as a proficient solution for this endeavor, offering a straightforward approach to this intricate calculation process.
Effects of Mn and Ru substitutions on the electrical properties and AC susceptibility of Tl(BaSr)CaCu2O7 superconductor
Authors: Muhammad-Aizat K. , Jumali M. H. , Jaafar N. A. N. , Abd-Shukor R.
Published: May 2024

In this paper, the effects of M = Mn and Ru substitutions at the Tl site of Tl[Formula: see text]Mx(BaSr)CaCu2O7 (Tl-1212) on the electrical properties and AC susceptibility were investigated. The X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM) methods were used to examine the phase and microstructure, respectively. All samples showed diffraction patterns with Tl-1212 as the major phase and an increase in the Tl-1223 phase with increasing Mn and Ru substitutions. The microstructure showed partial melting and randomly oriented grains in all samples. The electrical resistance measurements showed metallic normal state behavior for all samples. The zero-resistance transition temperature [Formula: see text] was the highest for x = 0.4 where [Formula: see text] was 107[Formula: see text]K and 90[Formula: see text]K for Mn and Ru substitutions, respectively. The superconducting transition, [Formula: see text] obtained from AC susceptibility measurements increased with Mn and Ru substitutions up to x = 0.4. Using Bean’s model, the current density at the peak temperature of the imaginary part of the AC susceptibility, [Formula: see text]([Formula: see text] was determined to be between 16 and 22[Formula: see text]A[Formula: see text]⋅[Formula: see text]cm[Formula: see text] for Mn, and between 15 and 19[Formula: see text]A[Formula: see text]⋅[Formula: see text]cm[Formula: see text] for Ru-substituted samples. Mn substitution showed a higher transition temperature compared with Ru. This study showed that optimization of the average Cu valence was achieved with Mn and Ru substitutions for x = 0.4 at the Tl site. The ionic radii of the substituting and substituted elements are important factors in enhancing the transition temperature of Tl(BaSr)CaCu2O7 superconductor.
Study of electronic, optical, thermodynamic, and thermoelectric properties of GeC bulk and monolayer structure
Authors: Goudarzi M. , Karamdel J. , Hassanabadi H. , Zorriasatein Sh.
Published: May 2024

Using density functional theory and Boltzmann equations, this study calculates and compares the electronic, optical, thermoelectric, and thermodynamic properties of bulk and single-layer germanium carbide structures. It has been shown that germanium carbide in the bulk structure has an indirect energy band gap of 1.61[Formula: see text]eV. In a single layer structure, it is a metal. Thermodynamic properties including specific heat at constant volume have been investigated using the quasi-harmonic approximation (QHA) package in QE. According to the studies conducted on optical properties, this material shows good reflection in the visible region. In addition, this structure has high electrical conductivity and low thermal conductivity, which is essential for thermoelectric materials. Thermoelectric calculations using semi-classical Boltzmann transfer theory show that the performance of two-dimensional compounds with graphene gives good thermoelectric results. At 100[Formula: see text]K, the highest figure of merit (ZT) for GeC is 1.00. Our findings evaluate the GeC compound as a suitable thermoelectric material in the temperature gradient from 100 to 900[Formula: see text]K.