bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancing the Thermal Performance of Solar Air Heaters using Heat Storage Medium: An Experimental Study with Energy, Exergy, and Economic Approach
Authors: Boudhiaf Ridha , Touhami Yassmin , Harby K. , Kabeel Abd Elnaby , Attia Mohamed El Hadi , Khelifa Abdelkrim , Latrache Noureddine , Driss Zied
Published: February 2025

A Solar Air Heater (SAH) is a simple device which collects solar radiation and transfers it to the processed air generally uses in several thermal engineering applications such as space and industrial process heating, and food drying, but its utilization is only during sunny hours. One of the most important methods of ameliorating its employing to heat air during the off-sunshine period is through the addition of heat storage medium inside the SAH for storing sun's radiation as thermal energy. The main objective of this experimental study is to predict the effect of the heat storage medium on the thermal performance of SAH. To achieve this goal, three different configurations of SAHs were designed and constructed in the Laboratory of Electro–Mechanic Systems, namely, Traditional SAH with natural circulation (T-SAH), SAH with a centrifugal air blower (F-SAH), and SAH with a centrifugal air blower and coupled with an internal heat storage medium (FS-SAH). They were tested and compared under the same ambient conditions of Sfax central–eastern Tunisia. Experimental results showed that the T-SAH gives higher temperatures than the F-SAH and FS-SAH during the period from 8 AM to 3 PM. From 3 PM to 7 PM, the temperatures of FS-SAH are the highest when compared with the other two SAHs. Through this period, the thermal energy per unit time obtained by FS-SAH, F-SAH and T-SAH is 2.15 kW, 0.23 kW and 0.086 kW, respectively.
Multiparametric ultrasound imaging of the urinary bladder beyond urine volume measurements. A pictorial essay.
Authors: Cokkinos Demosthenes D , Rafailidis Vasileios , Melissovas Ioannis , Beck Avi , Levitin Abraham , Partovi Sasan
Published: February 2025

Ultrasound of the urinary bladder detects diverse and complex pathology. This manuscript deals with various bladder diseases imaged with multiparametric ultrasound, including contrast enhanced ultrasound.
Chromosomal genes modulating fosfomycin susceptibility in uropathogenic
Escherichia coli
: a genome-wide analysis
Authors: Ma Yibing , Pirolo Mattia , Giarratana Lily , Leth Nielsen Karen , Häussler Susanne , Guardabassi Luca
Published: February 2025

Escherichia coli
acquires fosfomycin resistance through chromosomal mutations that reduce drug uptake and by drug-inactivating enzymes. However, the complete resistance mechanisms remain to be elucidated. The aim of this study was to elucidate the genetic mechanisms regulating fosfomycin susceptibility in uropathogenic
E. coli
(UPEC). We constructed a highly saturated transposon mutant library containing >340,000 unique Tn5 insertions in a clinical UPEC strain. We conducted transposon-directed insertion site sequencing (TraDIS) to screen for chromosomal genes whose mutations are beneficial for bacterial growth and survival in the presence of fosfomycin at 4 and 32 µg/mL. TraDIS analysis identified 67 genes including known resistance determinants (
n
= 13) as well as a set of novel genes modulating fosfomycin susceptibility (
n
= 54). These genes are involved in pyruvate metabolism, pentose phosphate pathway, nucleotide biosynthesis, DNA repair, protein translation, cellular iron homeostasis, and biotin biosynthesis. Deletion of 16 selected genes in the wild-type strain resulted in growth advantages and decreased susceptibility when exposed to fosfomycin. Notably, deletion of DNA repair genes (i.e.
, mutL
and
mutS
) and purine synthesis genes (i.e.,
purB
and its upstream gene
hflD
) led to the most significant advantages in competitive and non-competitive growth in the presence of fosfomycin, as well as the highest increase of fosfomycin MIC (8- to 16-fold). These findings provide a genome-wide overview of genes required for maintaining fosfomycin susceptibility in
E. coli
, highlighting new mutations and functional pathways that may be used by UPEC to develop clinical resistance.
Mono- and multidomain defense toxins of the RelE/ParE superfamily
Authors: Gerdes Kenn
Published: February 2025

Toxin–antitoxin (TA) modules are widely distributed across prokaryotes, often existing in large numbers despite their associated fitness costs. Most type II TA modules are bicistronic operons encoding a monodomain toxin and its cognate protein antitoxin. The RelE/ParE superfamily encompasses toxins with a conserved Barnase-EndoU-ColicinE5/D-RelE (BECR) fold. Yet, their cellular targets differ remarkably: RelE toxins function as ribosome-dependent RNases, while ParE toxins act as DNA gyrase inhibitors. Using a comprehensive bioinformatics approach, this study analyzed 13 BECR-fold toxin families as classified in the Pfam database. Intriguingly, the ParE family was found to include a subcluster of mRNA-cleaving toxins, challenging its conventional role as solely DNA-targeting. This study identified a novel tripartite operon encoding a PtuA-like defense ATPase, a homolog of type IV restriction endonucleases, and a RelE homolog, suggesting a coordinated role in defense mechanisms. Multidomain BECR-fold toxins, including transmembrane variants, were also discovered, extending the functional repertoire of type II TA modules to membrane-associated systems. These findings clarify the evolutionary relationships and functional diversity within the RelE/ParE superfamily and discover novel, putative defense systems that can now be investigated experimentally.

IMPORTANCE

Toxin–antitoxin modules play critical roles in prokaryotic survival and adaptation, contributing to genome stabilization and defense against phages and invading plasmids. The RelE/ParE superfamily exemplifies the structural and functional diversity of these systems, with members targeting distinct cellular processes, such as translation and DNA supercoiling. By elucidating the relationships among the 13 BECR-fold toxin families, this study enhances our understanding of microbial resistance mechanisms and reveals potential new opportunities for research into prokaryotic defense and regulation. These insights may have significant implications for medical and biotechnological applications, particularly in understanding bacterial responses to genetic invaders.
Endogenous nitric oxide promotes
Staphylococcus aureus
virulence by activating autophagy
Authors: Nurxat Nadira , Wang Qichen , Zhao Na , Guo Yanan , Zhang Xilong , Wang Yanan , Jian Ying , Wang Hua , Yang Shengbing , Li Min , Liu Qian
Published: February 2025

Endogenous nitric oxide (NO) is a small molecule that has been demonstrated to affect the physiology and survival of bacteria. The role of endogenous NO for
Staphylococcus aureus
survival inside host cells remains unclear. Here, we show that the production of endogenous NO by bacterial nitrate reductase (NR) is affected by molybdopterin biosynthesis protein A (MoeA), which is essential for molybdenum cofactor synthesis in
S. aureus
. During the infection, the production of endogenous NO promotes
S. aureus
survival inside macrophages by initiating cellular autophagy. Mechanistically, bacterial endogenous NO can modify the host regulatory protein thioredoxin vis S-nitrosylation, subsequently triggering the phosphorylation of the JNK-Bcl-2 pathway and promoting the initiation of autophagy through the release of Beclin1. Moreover, we confirmed the critical role of MoeA in bacterial survival
in vivo
by using bloodstream infection, pneumonia, and skin abscess model on both wild-type and autophagy-deficient mice. Interestingly, we observed the significantly increased production of NO and activation of cellular autophagy of sequence type (ST)5 compared with ST239, suggesting that the initiation of autophagy is involved in the clone shift of
S. aureus
. Our data offered new insights on the role of bacterial endogenous NO in regulating the host signal pathway during infection inside host cells.

IMPORTANCE

Understanding the mechanism underlying
Staphylococcus aureus
pathogenesis is essential for developing innovative strategies for the prevention and treatment of infection. In this study, we underscore the critical role of molybdopterin biosynthesis protein A and nitric oxide (NO) in inducing autophagy during
S. aureus
survival within macrophage and
in vivo
infection. We demonstrate that host regulatory protein can be modified by bacterial metabolites, which may influence cellular processes. Furthermore, our findings indicated that increased endogenous NO production may contribute to the stable prevalence of
S. aureus
ST5 in the healthcare-associated environment. These findings highlight the significance of bacterial metabolism in modulating the host immune system, thereby facilitating
S. aureus
survival and persistence.
Optimizing antibiotic use in MSSA bacteremia: a stewardship-focused approach
Authors: Campodónico Victoria L.
Published: February 2025

Antimicrobial stewardship is essential for optimizing therapy in bloodstream infections. Methicillin-susceptible
Staphylococcus aureus
(MSSA) bacteremia requires prompt beta-lactam treatment, and delays in transitioning from empirical anti-MRSA therapy can result in adverse outcomes. Rapid diagnostics like the BioFire Blood Culture Identification (BCID) PCR panel, combined with stewardship interventions, significantly improve care by reducing unnecessary broad-spectrum antimicrobial use. A study by Yetukuri et al. demonstrated that integrating BCID with stewardship efforts reduced time to optimal therapy by 20 h (49 vs 29.1 h,
P
< 0.001) and shortened both bacteremia duration and anti-MRSA therapy without affecting mortality or hospital stay. These findings emphasize that stewardship programs, including real-time reviews and prescriptive guidance, are critical for translating rapid diagnostic results into timely, targeted treatment. Leveraging stewardship with advanced diagnostics offers a strategic approach to enhancing outcomes and combating antimicrobial resistance.
Laparoscopic approach to inguinal hernia with incarcerated ovary in a patient with endometrial neoplasia
Authors: Serrano Molina Alba María , Gutiérrez Carmen , Carreño-Sáenz Omar , Pous-Serrano Salvador
Published: February 2025

Ovarian inguinal herniation is a rare clinical entity. It can be safely managed laparoscopically, even in patients with concurrent gynaecological malignancies requiring radical hysterectomy.

We present the case of a middle-aged woman admitted for severe anaemia and progressive weakness. Imaging revealed endometrial cancer and a right inguinal hernia containing an 8 cm lesion of indeterminate origin. MRI identified strangulated ovarian tissue within the hernia, and histopathology confirmed a low-grade endometrioid adenocarcinoma.

The patient underwent a planned laparoscopic procedure, including radical hysterectomy, sentinel lymph node biopsy and simultaneous inguinal hernia repair. The hernia was repaired using the transabdominal preperitoneal approach after excision of the right adnexa, with polyvinylidene fluoride mesh fixation. The patient experienced an uneventful recovery and was discharged on the second postoperative day.

Histopathological analysis confirmed low-grade endometrioid carcinoma with clear margins and metastasis in two lymph nodes, demonstrating the feasibility of managing both conditions concurrently.
Pulmonary artery stenting for palliative treatment of refractory hypoxaemia in a patient with small cell lung cancer
Authors: Iftikhar Mian Harris , Smith Kyler , Dar Aneeqa Yousaf , Parikh Raj
Published: February 2025

Pulmonary artery stenosis (PAS) is most encountered in the paediatric population as a congenital anomaly. In adults, PAS from extrinsic compression of the pulmonary artery (PA) results from conditions such as fibrosing mediastinitis, malignancy, infections and anastomotic stenosis after lung transplantation. We describe a woman in her 50s with extensive stage small cell lung cancer who presented with symptoms of shortness of breath and hypoxaemic respiratory failure. CT angiography chest showed a progressively enlarging mediastinal mass causing severe compressive stenosis of the right PA and moderate stenosis of the left PA. Her symptoms did not improve despite using bronchodilators and intravenous steroids. Pulmonary angiography confirmed clinically significant stenosis of her right PA. The placement of a single stent within the right PA provided significant improvement in symptoms and supplemental oxygen requirement within 24 hours.
Antenatal diagnosis and early postnatal management of a neonate with type 1 familial glucocorticoid deficiency
Authors: Chougula Priyadarshini Virupaxi , Deshpande Sujata , Datar Chaitanya , Suryawanshi Pradeep
Published: February 2025

Familial glucocorticoid deficiency (FGD) is a rare inherited cause of primary adrenal insufficiency, characterised by cortisol deficiency, without mineralocorticoid involvement. Affected patients commonly present in infancy or early childhood with hypoglycaemia, seizures, generalised hyperpigmentation and failure to thrive. Late diagnosis may lead to adverse neurological outcomes, usually resulting from repeated hypoglycaemic episodes. A family history of sibling deaths or affected relatives is often observed. Mutations in the gene encoding adrenocorticotropin receptor (melanocortin 2 receptor,MC2R), comprise about 25% of FGD cases (type 1 FGD). Here, we describe an infant born to parents with third-degree consanguinity and a history of unexplained neonatal deaths in two previous siblings, who had hyperpigmentation and hypoglycaemia. Genetic testing revealed both parents to be heterozygous for theMC2Rgene variant c.701C>C/T (p.Pro234Leu). In the current pregnancy, amniocentesis performed for prenatal diagnosis confirmed the fetus to be homozygous for the same mutation as the parents, indicating the fetus would be affected with type I FGD. After birth, the infant was managed in the neonatal intensive care unit, and despite markedly low cortisol levels, prompt initiation of glucocorticoid replacement therapy resulted in the prevention of hypoglycaemia and adrenal crisis, with a favourable outcome. Our case is unique due to the antenatal diagnosis of FGD, allowing for proactive postnatal management and prevention of complications.
Effectiveness of reducing tendon compression in the rehabilitation of insertional Achilles tendinopathy: a randomised clinical trial
Authors: Pringels Lauren , Capelleman Robbe , Van den Abeele Aäron , Burssens Arne , Planckaert Guillaume , Wezenbeek Evi , Vanden Bossche Luc
Published: February 2025

Objective

To assess the effectiveness of low tendon compression rehabilitation (LTCR) versus high tendon compression rehabilitation (HTCR) for treating patients with insertional Achilles tendinopathy.

Methods

In an investigator-blinded, stratified randomised trial, 42 sport-active patients (30 males and 12 females; age 45.8±8.2 years) with chronic (> 3 months) insertional Achilles tendinopathy were allocated in a 1:1 ratio to receive LTCR or HTCR. Both rehabilitation protocols consisted of a progressive 4-stage tendon-loading programme, including isometric, isotonic, energy-storage and release and sport-specific exercises. The LTCR programme was designed to control Achilles tendon compression by limiting ankle dorsiflexion during exercise, eliminating calf stretching and incorporating heel lifts. The primary outcome was the Victorian Institute of Sports Assessment-Achilles (VISA-A) score at 12 and 24 weeks, which measures tendon pain and function and was analysed on an intention-to-treat basis using a linear mixed model. Significance was accepted when p<0.05.

Results

20 patients were randomised to the LTCR group and 22 to the HTCR group. Improvement in VISA-A score was significantly greater for LTCR compared with HTCR after 12 weeks (LTCR=24.4; HTCR=12.2; mean between-group difference=12.9 (95% CI: 6.2 to 19.6); p<0.001) and after 24 weeks (LTCR=29.0; HTCR=19.3; mean between-group difference=10.4 (95% CI: 3.7 to 17.1); p<0.001). These differences exceeded the minimal clinically important difference of 10.

Conclusions

In sport-active patients with insertional Achilles tendinopathy, LTCR was more effective than HTCR in improving tendon pain and function at 12 and 24 weeks. Consequently, LTCR should be considered in the treatment of insertional Achilles tendinopathy.

Trial registration number

ClinicalTrials.gov (ID:NCT05456620).
Protocol for a systematic review and network meta-analysis comparing the efficacy and safety of benzalkonium chloride-preserved, alternatively preserved and preservative-free eyedrops in the treatment of glaucoma
Authors: Kim Myungjin , Kim Young Kook , Rho Seungsoo , Ha Ahnul
Published: February 2025

Introduction

The primary therapeutic approach to glaucoma involves the long-term use of intraocular pressure (IOP)-lowering eyedrops. However, the prevalent use of benzalkonium chloride (BAK) as a preservative in glaucoma eyedrops has been associated with ocular side effects, prompting a demand for alternatively preserved (AP) or preservative-free (PF) eyedrops. Studies comparing various preservatives have shown conflicting evidence concerning the safety of BAK-preserved (BP) eyedrops, some studies indicating no notable concerns and others reporting adverse effects. The current protocol concerns a network meta-analysis enabling systematic investigation of the IOP-lowering efficacy and safety profiles of BP, AP and PF eyedrops in patients with glaucoma for whom randomised controlled trials (RCTs) are available.

Methods and analysis

This study will evaluate the IOP-lowering effects of glaucoma eyedrops, comparing formulations with and without preservatives in patients with glaucoma. A systematic search for RCTs, regardless of language or publication date, will be conducted across three electronic databases (Cochrane search engine, Embase and MEDLINE) from 1 March 2024. Two reviewers will conduct a sequential screening of titles and abstracts, followed by full-text papers, to extract useful data. The two reviewers will also assess the internal validity of studies using the relevant and domain-based risk of bias assessment tool. Overall evidence quality will be assessed using the Confidence in Network Meta-Analysis approach and presented in summarised form with network diagrams. Forest plots will be generated for enhanced visualisation of the included glaucoma eyedrops’ effects, and pairwise effect sizes will be calculated based on available evidence in the network.

Ethics and dissemination

No ethics review or approval is required for this work, as it will synthesise evidence obtained from published studies. A paper presenting the findings will be submitted to a peer-reviewed journal for publication.

PROSPERO registration number

CRD42024498328
The state of youth sexual and reproductive health problems and service utilisation in major towns of Ethiopia: a cross-sectional study
Authors: Dadi Tegene Legese , Medhin Girmay , Fentaye Fasil Walelign , Tadesse Daniel , Tassew Setegn Tigabu , Wakene Tigist Urgessa , Haddis Dereje , Lemma Israel , Andualem Wasihun , Tiruneh Chalachew Alemu , Alemayehu Yibeltal Kiflie
Published: February 2025

Objectives

The study aimed to assess the prevalence of reproductive health problems among youths and the utilisation of services and associated factors in urban Ethiopia.

Design

This paper presents findings related to sexual and reproductive health (SRH) based on a formative assessment of the Integrated Youth Activity which is conducted by cross-sectional study.

Setting

Youths from community and higher education institutions were included from 13 major urban towns of Ethiopia in the study.

Participants

A total of 1954 youths from community settings were included from randomly selected eligible households and 1261 students were included from higher education institutions.

Primary outcomes

The youths’ experience of unwanted pregnancy; exposure to high-risk sexual behaviour (HRSB); SRH service utilisation; and current use of family planning (FP) services.

Results

Among youths, 35% have engaged in HRSB, more than 14% have experienced at least one unwanted pregnancy and 26.7% have used SRH services. Additionally, only 26.4% of female youths use FP. The uptake of SRH services is lower among unmarried youths, those aged 18–19, individuals with no access to mass media and those who do not encounter SRH messages. Unintended pregnancy among women is common among those in higher education, lacking comprehensive HIV knowledge and engaging in HRSB. HRSB is prevalent among youths with no education, aged 18–19, who have not used SRH or FP services, and those with multiple social media accounts.

Conclusion

A relatively high proportion of youths exhibit low uptake of SRH and FP services, with a higher proportion exposed to HRSB and unintended pregnancy. Barriers to the utilisation of SRH services as well as increased risk of HRSB, including unwanted pregnancies, are often linked to poor access to accurate and relevant SRH information. To address this gap, delivering targeted SRH-related messages through social media and mass media broadcasts can play a transformative role. This approach not only broadens youth access to reliable SRH information but also enhances their health literacy by increasing the credibility and relevance of the information provided.
Clinical pharmacist-led medication reconciliation supplemented with medication review in admitted patients with chronic kidney disease: a cost-benefit analysis
Authors: Altawalbeh Shoroq M , Sallam Nahlah M , Al-Khatib Minas , Alshogran Osama Y , Bani Amer Mohammad S
Published: February 2025

Objective

Chronic kidney disease (CKD) is associated with a high economic burden, which is exacerbated by the high susceptibility to drug-related problems (DRPs) in this patient population. This study aimed to evaluate the cost-benefit ratio of medication reconciliation supplemented with medication review for inpatients with CKD, compared with the absence of this intervention.

Design

This was a cost-benefit analysis conducted along with a prospective interventional study.

Setting

The study was conducted at two hospitals in Jordan between February and May 2023.

Participants

The prospective interventional study included 142 admitted patients with CKD.

Interventions

Patients received medication reconciliation at admission and discharge as well as medication review throughout admission.

Primary and secondary outcome measures

The primary outcome measures were the net benefit and the benefit-to-cost ratio of the intervention. A cost-benefit analysis was conducted from the healthcare system perspective by assessing the cost of the service (the pharmacist time required to complete the service per patient) and the economic benefit, including total and per-patient cost savings and cost avoidance.

Results

The total estimated cost of all DRPs in the absence of interventions (cost avoidance) was $83 052 (average of $585±308 per patient); among which $20 623 was attributed to medication discrepancies. The cost savings were estimated at –$467. The supplemented medication reconciliation service was estimated to cost $714. As a result, the estimated net benefit totalled $81 871, averaging $577 per patient, with a benefit-to-cost ratio of 115.7:1 over the 4-month study period.

Conclusions

Delivering a supplemented medication reconciliation service by a clinical pharmacist for patients with CKD is cost beneficial from the healthcare perspective in Jordan, an example of a low- and middle-income country. This finding further confirms the pivotal role of clinical pharmacists in multidisciplinary healthcare teams.
Midpalatal suture osteotomy combined with microimplant-assisted rapid palatal expansion for adult maxillary transverse deficiency treatment: a study protocol of a randomised controlled trial
Authors: Zhang Wenyi , Chung Miri , Zhu Yanfei , Qian Yifeng , Zhang Lei , Jiang Lingyong
Published: February 2025

Introduction

Maxillary transverse deficiency (MTD) is a common type of malocclusion. For adult MTD patients with highly ossified midpalatal sutures, surgically assisted rapid palatal expansion (SARPE) has been the conventional method of maxillary expansion. However, SARPE has the disadvantages of significant trauma, high cost and a high incidence of adverse events. Therefore, we proposed a novel minimally invasive method for maxillary expansion, which is midpalatal suture osteotomy combined with microimplant-assisted rapid palatal expansion (MSO-MARPE). The results are expected to confirm MSO-MARPE as a novel minimally invasive alternative to SARPE in skeletally mature MTD patients.

Methods and analysis

A prospective, single-centre, parallel-group randomised controlled trial will be conducted, enrolling 20 adult MTD patients. Participants will be randomised equally to the control and experimental groups. The control group will undergo a Lefort I and median osteotomy and postoperative maxillary expansion with a tooth-borne Hyrax-type expander. The experimental group will undergo a midpalatal suture osteotomy and postoperative maxillary expansion with a microimplant-assisted expander. A series of linear and angular parameters will be measured in the pre- and post-coronal planes before treatment (T0), immediately after expansion (T1) and 6 months after expansion (T2) to evaluate the efficacy of skeletal expansion and dental side effects. The study aims to compare the clinical and cost-effectiveness of SARPE and that of MSO-MARPE. The primary outcome is the contribution of posterior midpalatal expansion immediately after expansion. The secondary outcomes include nasal, sutural, alveolar and dental expansion, pain intensity, operative time and treatment costs. The safety indicator will be the number and incidence of adverse events. The interaction between the control group and the experimental group will be analysed using two independent-sample t-tests or Mann–Whitney U test, and the paired data at different time points will be analysed using paired t-test.

Ethics and dissemination

The trial protocol (version 6.0 13 December 2024) has been approved by the Institutional Review Board of the Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine (approval number: SH9H-2023-T309-3). Results will be disseminated through peer-reviewed publications and presentations at scientific conferences.

Trial registration number

ChiCTR2400081545.
APPROACH: Analysis of Proton versus Photon Radiotherapy in Oligodendroglioma and Assessment of Cognitive Health – study protocol paper for a phase III multicentre, open-label randomised controlled trial
Authors: Slevin Finbar , Hudson Eleanor Mae , Boele Florien W , Powell James R , Noutch Samantha , Borland Myfanwy , Brown Sarah , Bruce Anna , Bulbeck Helen , Burnet Neil G , Chang Yen Ching , Colaco Rovel , Currie Stuart , Egleston Daniel , Fersht Naomi , Klein Martin , Lilley John , Lowe Matthew , Miles Elizabeth , Murray Robert D , O’Hara Daniel J , Norris Matthew , Parbutt Catherine , Smith Alexandra , Smith Charlotte , Whitfield Gillian A , Short Susan , Murray Louise
Published: February 2025

Introduction

Oligodendroglioma (ODG) is a rare type of brain tumour, typically diagnosed in younger adults and associated with prolonged survival following treatment. The current standard of care is maximal safe debulking surgery, radiotherapy (RT) and adjuvant procarbazine, lomustine and vincristine (PCV) chemotherapy. Patients may experience long-term treatment-related toxicities, with RT linked to impairments of neurocognitive function (NCF) and health-related quality of life (HRQoL). With proton beam therapy (PBT), radiation dose falls off sharply beyond the target with reduced normal brain tissue radiation doses compared with photon RT. Therefore, PBT might result in reduced radiation-induced toxicity compared with photon RT.

Methods and analysis

APPROACH is a multicentre open-label phase III randomised controlled trial of PBT versus photon RT in patients with ODG, investigating the impact of PBT on long-term NCF measured using the European Organisation for Research and Treatment of Cancer (EORTC) Core Clinical Trial Battery Composite (CTB COMP). The trial will randomise 246 participants from 18 to 25 UK RT sites, allocated 1:1 to receive PBT or photon RT, with PBT delivered at one of the two UK PBT centres. Participants with grade 2 and grade 3 ODG will receive 54 Gy in 30 fractions and 59.4 Gy in 33 fractions, respectively, followed by 6×6-weekly cycles of PCV chemotherapy. The trial contains staged analyses, with an internal pilot for feasibility of recruitment at 12 months, early assessment of efficacy at 2 years, futility assessment and final primary endpoint comparison of NCF between arms at 5 years. Secondary endpoints include additional NCF, treatment compliance, acute and late toxicities, endocrinopathies, HRQoL, tumour response, progression-free survival and overall survival.

Ethics and dissemination

Ethical approval was obtained from Newcastle North Tyneside REC (reference 22/NE/0232). Final trial results will be published in peer-reviewed journals and adhere to International Committee of Medical Journal Editors (ICMJE) guidelines.

Trial registration number

ISRCTN:13390479.
Heart failure in low-income and middle-income countries
Authors: Mbanze Irina , Spracklen Timothy F , Jessen Neusa , Damasceno Albertino , Sliwa Karen
Published: February 2025

Heart failure (HF) is a complex syndrome which leads to significant morbidity and mortality, poor quality of life and extremely high costs to healthcare systems worldwide. Although progress in the management of HF in high-income countries is leading to an overall reduction in the incidence and mortality of HF, there is a starkly different scenario in low- and middle-income countries (LMICs). There is a substantial lack of data on HF in LMICs, as well as a scarcity of diagnostic tools, limited availability and affordability of healthcare and high burdens of cardiovascular risk factors and communicable diseases. Patients in this setting present with more advanced HF at much younger ages and are, more often, women. In this review, we aim to comprehensively describe the burden of HF from an LMIC perspective, based on the more recent available data. We summarise the major causes of HF that are endemic in these regions, including hypertension, cardiomyopathy, rheumatic heart disease, HIV-associated heart disease and endomyocardial fibrosis. Finally, we discuss the challenges faced by the least developed health systems and highlight interventions that may prove to be more efficient in changing the paradigm of HF of the more vulnerable populations.
Association of 5α-reductase inhibitor prescription with immunotherapy efficacy in metastatic renal cell carcinoma: a multicenter retrospective analysis
Authors: Cheng Bisheng , Wu Jilin , Chen Ke , Li Weijia , Yang Jianghua , Shangguan WenTai , Yang Lin , Huang Wenxue , Ma Cunzhen , Li Zhuohang , Sun Boyuan , Wang Qiong , Huang Hai , Wu Peng
Published: February 2025

Background

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC), but response rates remain heterogeneous, and reliable predictive biomarkers are lacking. Recent studies suggest that androgen receptor (AR) signaling plays a role in regulating CD8+T-cell function, implying that 5α-reductase inhibitors (5-ARIs), which lower androgen activity, could enhance antitumor immunity and improve clinical outcomes in patients receiving immunotherapy. This study retrospectively investigates the impact of a history of 5-ARI use (≥12 months) on the efficacy of ICIs in mRCC.

Methods

We conducted a multicenter retrospective cohort study of 185 patients with mRCC who received ICIs. Patients were stratified based on their history of 5-ARI use. Baseline characteristics included age, body mass index, International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group, programmed death-ligand 1 (PD-L1) expression levels, tumor stage, and metastasis sites. The primary endpoints were progression-free survival (PFS) and overall survival (OS), analyzed using Cox proportional hazards models. Secondary endpoints included objective response rate (ORR) and disease control rate (DCR). Key immunological insights were gained through single-cell RNA sequencing analysis of tumor samples.

Results

Patients with a history of 5-ARI use demonstrated improved ORR (59.8% vs 39.8%, p=0.0075) and DCR (87.0% vs 78.7%, p=0.1747) compared with those without. The median PFS and OS were significantly longer in the 5-ARI group, with HRs of 0.64 (95% CI: 0.47 to 0.86, p=0.0085) for PFS and 0.65 (95% CI: 0.47 to 0.90, p=0.0271) for OS. Subgroup analysis further indicated enhanced ICI efficacy with 5-ARI use across age, IMDC risk scores, and PD-L1 expression levels. Single-cell RNA sequencing analysis revealed that 5-ARI treated patients exhibited a reduced presence of regulatory T cells and CD8 T-cell exhaustion (CD8 Tex), and lower programmed cell death protein-1 expression in CD8 Tex cells, suggesting an immunologically favorable modification of the tumor.

Conclusion

A history of 5-ARI use is associated with improved responses to ICI therapy in mRCC, potentially through AR-related modulation of CD8+T-cell activity and favorable alterations in the immune microenvironment. These findings support further investigation into androgen-targeted approaches as adjunctive strategies in immunotherapy for RCC.
No short-term changes in tendon structure following temporary replacement of running with low-impact exercises in service members with midportion Achilles tendinopathy: a prospective cohort study
Authors: Paantjens M A , Helmhout P H , Martens M T A W , Lentjes G W , Bakker E W P
Published: February 2025

Introduction

Midportion Achilles tendinopathy (mid-AT) is associated with tendon degeneration that may worsen due to mechanical loading. Contrastingly, load can also improve tendon structure. We aimed to evaluate short-term changes in midportion tendon structure and their associations with symptoms, following temporary replacement of running with low-impact exercises on a stair climber or cross-trainer, in service members with mid-AT.

Methods

We recruited 40 service members (40 symptomatic tendons) for this study. Ultrasound tissue characterisation (UTC) was used to quantify aligned fibrillar structure (echo-type I+II) and disorganised structure (echo-type III+IV), in the tendon midportion (2–7 cm) and in the area of maximum degeneration (AoMD) within the midportion. Symptoms were evaluated with the modified Victorian Institute of Sports Assessment – Achilles (VISA-A) questionnaire. All measurements were performed at baseline and after 8 weeks. The Wilcoxon signed-rank test was used to evaluate differences in UTC and VISA-A. Spearman’s rho was used to calculate the correlations between UTC and VISA-A change scores.

Results

Tendon structure did neither change significantly in the midportion: echo-type I+II from median 64.7% (IQR 19.4) to 68.6% (IQR 25.1) (p=0.793); echo-type III+IV from median 35.3% (IQR 19.4) to 31.5% (IQR 25.1) (p=0.775) nor in the AoMD: echo-type I+II from median 56.3% (IQR 18.0) to 57.9% (IQR 32.0) (p=0.677); echo-type III+IV from median 43.8% (IQR 18.0) to 42.3% (IQR 32.1) (p=0.572).

On the other hand, VISA-A improved significantly (p=0.000) from baseline (median 46.5, IQR 16.0) to follow-up (median 56.0, IQR 9.0). Correlations between UTC and VISA-A change scores were consistently graded as low (range: 0.309–0.338).

Conclusions

Although the replacement of running with low-impact exercises improved symptoms, no changes in tendon structure were observed after 8 weeks. Changes in midportion structure and symptoms were poorly associated. These findings can support loading advice in patients with mid-AT when aiming to prevent progressive degeneration or tendon rupture.

Trial registration number

NL69527.028.19, "Centrale Commissie Mensgebonden Onderzoek" (CCMO).
Cardiovascular mortality among seafarers: a Danish nationwide cohort study
Authors: Bøge Anna Uhd , Möller Sören , Lindahl-Jacobsen Rune , Froholdt Lisa Loloma , Herttua Kimmo , Ahrenfeldt Linda Juel
Published: February 2025

Objectives

Cardiovascular disease (CVD) is the leading cause of death globally and the second most frequent cause of death in Denmark. Due to their unique occupational environment, seafarers are exposed to numerous risk factors for CVD including lifestyle and work-related factors. This study aims to investigate CVD mortality among Danish seafarers by comparing them to the economically active reference population.

Methods

This register-based cohort study included data on all Danish seafarers from 1993 to 2016 and compared them with the economically active Danish population not working as seafarers. The seafarers’ mortality was calculated using piecewise stratified Cox regression adjusting for potential confounders. Mortality was further analysed by diagnosis groups, vessel type and employment duration.

Results

Among 52 861 seafarers, 4226 deaths were observed, with 866 (20.5%) of these attributed to CVD. Male seafarers had higher all-cause mortality in age groups 18–44 years (HR 1.46, 95% CI 1.33 to 1.62), 45–64 years (HR 1.43, 95% CI 1.37 to 1.50) and 65+ years (HR 1.32, 95% CI 1.26 to 1.39) compared with the reference population. CVD mortality was increased for male seafarers aged 45–64 years (HR 1.27, 95% CI 1.13 to 1.42) and 65+ years (HR 1.34, 95% CI 1.21 to 1.48). The mortality was higher for male seafarers for ischaemic heart diseases, other forms of heart diseases, cerebrovascular diseases and diseases of arteries, arterioles and capillaries. CVD mortality was also observed based on vessel type.

Conclusions

The study provides evidence of elevated CVD mortality among Danish seafarers. Future research should focus on identifying effective strategies to improve the cardiovascular health of seafarers.
Lung ultrasound outperforms symptom-based screening to detect interstitial lung disease associated with rheumatoid arthritis
Authors: Vermant Marie , Kalkanis Alexandros , Jacob Joseph , Goos Tinne , Cortesi Emanuela Elsa , Cypers Heleen , De Crem Nico , Follet Tine , Gogaert Stefan , Neerinckx Barbara , Taelman Veerle , Veyt Nathalie , De Sadeleer Laurens J , Verschueren Patrick , Wuyts Wim
Published: February 2025

Objectives

Interstitial lung disease associated with rheumatoid arthritis (RA-ILD) is linked to high mortality. Currently, effective screening tools are lacking. We assessed the role of symptoms and lung ultrasound (LUS) as potential screening tools.

Methods

116 adult patients with RA presenting to the rheumatology outpatient clinic underwent high-resolution CT (HRCT) scans, pulmonary function tests, LUS (72 zones) and completed a Visual Analogue Scale (VAS) for cough and modified Medical Research Council dyspnoea scale (mMRC). Kruskal-Wallis (KW) tests evaluated the correlation between clinical–radiological HRCT score (no ILD, non-specific abnormalities, subclinical ILD or ILD) and the B-lines on LUS, diffusion capacity (DLCO%pred), forced vital capacity (FVC%pred), VAS Cough and mMRC. Sensitivity and specificity analyses were performed to assess symptom-based questionnaires and the number of B-lines to detect RA-ILD. Area under the receiver operating characteristics (AUROC) for detecting clinical ILD and subclinical ILD were calculated.

Results

In 11.8% of patients, an ILD was detected on HRCT. Additionally, in 5%, a diagnosis of subclinical interstitial lung changes was made. The number of B-lines was most strongly associated with the clinical–radiological score (KW χ²=41.2, p=<0.001). DLCO%pred was also significantly correlated with the clinical–radiological score (KW χ²=27.4, p=<0.001), but FVC%pred, mMRC and VAS cough were not. Cough and dyspnoea only weakly predicted the ILD score in the sensitivity–specificity analyses, while B-lines showed AUROCs>0.9 for predicting subclinical and clinical ILD.

Conclusion

LUS is a promising tool for early detection of RA-ILD, outperforming symptom-based questionnaires or the presence of dyspnoea or cough.
Explainable models for predicting long-term outcomes in patients with spontaneous intracerebral haemorrhage: a retrospective cohort study
Authors: Yang Kai-Cheng , Jin Yu-Jia , Tang Li-Li , Gao Feng , Tong Lusha
Published: February 2025

Background and aim

Recently, long-term outcomes in patients with spontaneous intracerebral haemorrhage (sICH) have gained increasing attention besides acute-phase characteristics. Predictive models for long-term outcomes are valuable for risk stratification and treatment strategies. This study aimed to develop and validate an explainable model for predicting long-term recurrence and all-cause death in patients with ICH, using clinical and imaging markers of cerebral small vascular diseases from MRI.

Method

We retrospectively analysed data from a prospectively collected large-scale cohort of patients with acute ICH admitted to the Neurology Department of The Second Affiliated Hospital of Zhejiang University between November 2016 and April 2023. After comprehensive variable selection using least absolute shrinkage and selection operator and stepwise Cox regression, we constructed Cox proportional hazards models to predict recurrence and all-cause death. Model performance was evaluated using the concordance index, integrated Brier score and time-dependent area under the curve. Global and local interpretability were assessed using variable importance calculated as SurvSHAP(t) and SurvLIME methods for the entire training set and individual patients, respectively.

Results

A total of 842 eligible patients were included. Over a median follow-up of 36 months (IQR: 12–51), 86 patients (9.1%) died, and 62 patients (6.6%) experienced recurrence of ICH. The concordance indexes for the all-cause death and recurrence models were 0.841 (95% CI 0.767 to 0.913) and 0.759 (95% CI 0.651 to 0.867), respectively, with integrated Brier scores of 0.079 and 0.063. The interpretability maps highlighted age, aetiology of ICH and low haemoglobin as key predictors of long-term death, while cortical superficial siderosis and previous haemorrhage were crucial for predicting recurrence.

Conclusions

This model demonstrates high predictive accuracy and emphasises the crucial factors in predicting long-term outcomes of patients with sICH.
Co-inoculation of beneficial microorganisms in upland rice cultivated at different phosphorus levels
Authors: Asobia Princewill C. , Paula Kássia L. M. , Oliveira Maythsulene I. , Bittencourt Caroline D. , Wendland Adriane , Ferreira Enderson
Published: February 2025

Beneficial microorganisms can sustainably improve rice production. This study characterized IAA-producing and P-solubilizing bacteria, investigating their impact on upland rice through single or co-inoculation. Four bacterial strains (BRM 063573, BRM 67205, BRM 063574, and BRM 67206) were identified by 16S rRNA gene sequencing. A greenhouse experiment was arranged in a 20x3 factorial design with four replications. The first factor included 18 bacterial combinations and two controls (without fertilization or inoculant, and with fertilization but no inoculant). The second factor tested three phosphorus doses (25%, 50%, and 100% of the recommended P dosage). Growth and productivity parameters were determined. Based on the 16S rRNA gene sequencing, the bacteria BRM 063574 was closely related to Stenotrophomonas maltophilia, while BRM 063573 and BRM 67206 were closely related to Bacillus pumilus and BRM 67205 was closely related to Paenibacillus pabuli. Co-inoculation treatments generally outperformed single inoculations, improving performance in number of tillers, plant height, root volume, root weight and shoot weight. Single inoculation and co-inoculation had different effects on number of pods, number of full grain and grain weight, with co-inoculation consistently giving better results. The variability in response to single inoculation suggests an inconsistency in the performance of single inoculants. Co-inoculation, on the other hand, consistently offered advantages, improving the number of pods, number of full grains and grain weight at different phosphate doses. Based on grain production, the co-inoculants BRM 67207+BRM 67206 and BRM 67207+BRM 063574 are most promising for use as rice inoculants, offering consistent benefits for improving yield.
The Effective Use of Online Discussion Forums
Authors: Schmidt Steven
Published: February 2025

Discussion forums have become a standard element of online courses for a variety of reasons. They provide a way for students and faculty to interact with each other and to discuss course topics effectively and efficiently. Discussions can be separated by thread, meaning multiple discussions can occur at the same time. The asynchronous nature of discussion forums allows students and faculty to review posts and contribute to discussions at any time they are able to do so. They can also meet student needs for socialization and interaction, providing them with a sense of belonging that may be otherwise difficult to achieve in an online course. This article will focus on the use of discussion forums in online education. It will include content on best practices, limitations, and issues to be aware of when using discussion forums in online courses.
Attention-Mechanism-Based Neural Latent-Factorization-of-Tensors Model
Authors: Xu Xiuqin , Lin Mingwei , Xu Zeshui , Luo Xin
Published: February 2025

High-Dimensional and Incomplete (HDI) tensors contain a wealth of knowledge and patterns, which are typically utilized to characterize complex relationships between entities in a variety of industrial applications. Currently, the neural network-based tensor factorization model has shown superiority when handling the missing data in HDI tensors. However, it only uses the outer product of latent factors of entities and neglects the interactions between the latent factor (LF) vectors. In addition, the simple linear operation does not consider the nonlinear structure of the HDI tensor. To overcome the aforementioned issues, an Attention-mechanism-based Neural Latent-Factorization-of-Tensors (ANLFT) model is provided in this paper. It encompasses three primary ideas: a) incorporating the theory of neural networks with the latent factorization of tensor to construct the nonlinear structure in the HDI tensor effectively; b) adopting the attention mechanism of the LF vectors to depict the interactions between entities; c) using the position-transitional particle swarm optimization backward propagation learning (

\(\rm{P}^{2}\)

BP) scheme to train the ANLFT model efficiently. The experimental results on eight HDI datasets show that the ANLFT model can obtain higher estimation performance gain than state-of-the-art models. The convergence performance of the proposed model is also competitive with that of state-of-the-art models.