bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic performance of axial T2-weighted MRI sequence for exclusion of brain tumour in paediatric patients with non-localizing symptoms
Authors: Gerrish Amy C , Malik Luqman , Swain Charlotte , Thomas Adam G , Jaspan Timothy , Dineen Rob A 
Published: December 2024

Abstract

Objective
To establish diagnostic performance of a single axial T2-weighted sequence for detection of brain tumours in children with non-localizing symptoms, compared to a standard MRI protocol.

Methods
Retrospective analysis of children undergoing MRI brain imaging for suspected brain tumours with non-localizing symptoms over a 3-year period. Axial T2-weighted images were blindly reviewed by 2 experienced paediatric neuroradiologists. Primary analysis was calculation of diagnostic performance metrics for tumour identification using axial T2-weighted image only compared to the standard MRI protocol.

Results
For 312 children undergoing MRI brain during the study period, sensitivity and specificity for brain tumour detection based on axial T2-weighted images in children with non-localizing symptoms were 1.000 (95% CIs 0.598, 1.000) and 0.998 (95% CI 0.990, 0.999), respectively. Based on T2-weighted images alone, 50 patients (16%) were flagged as needing recall for further imaging compared to 14 (4.5%) recalled after the standard protocol.

Conclusions
Axial T2-weighted images have high sensitivity and specificity for detection of brain tumours in children with non-localizing symptoms but are associated with increased imaging recall rates. Prospective evaluation of this approach to identify patients requiring more comprehensive imaging is warranted.

Advances in knowledge
A truncated MRI protocol with single axial T2-weighted sequence has high diagnostic performance for brain tumour detection in children with non-localizing features. Radiologists can be reassured that a child with this presentation who is unable to complete the full MRI scan protocol is very unlikely to have a brain tumour missed provided an axial T2-weighted sequence is obtained.
Clearance of beta-amyloid and tau aggregates is size dependent and altered by an inflammatory challenge
Authors: Fertan Emre , Hung Christy , Danial John S H , Lam Jeff Y L , Preman Pranav , Albertini Giulia , English Elizabeth A , Böken Dorothea , Livesey Frederick J , De Strooper Bart , Patani Rickie , Klenerman David 
Published: December 2024

Abstract
Extracellular beta-amyloid aggregation and inflammation are in a complex and not fully understood interplay during hyperphosphorylated tau aggregation and pathogenesis of Alzheimer’s disease. Our group has previously shown that an immune challenge with tumour necrosis factor alpha can alter extracellular beta-sheet containing aggregates in human-induced pluripotent stem cell-derived cortical neurons carrying familial Alzheimer’s disease-related presenilin 1 mutations. Here, using single-molecule detection and super-resolution imaging techniques, we quantified and characterized the intra- and extracellular beta-amyloid and AT8-positive tau aggregates. Our results indicate a pre-existing Alzheimer’s disease-like pathology caused by the presenilin 1 mutation, with increased beta-amyloid aggregates in both the cell lysate and conditioned media compared to isogenic controls and also increased intracellular tau aggregates. The main effect of tumour necrosis factor alpha treatment on presenilin 1 neurons was the formation of larger intracellular beta-amyloid aggregates. In contrast, isogenic controls showed more significant changes with tumour necrosis factor alpha treatment with an increase in beta-amyloid aggregates in the media but not intracellularly and an increase in tau aggregates in both the media and cell lysate, suggesting a chronic inflammation-driven mechanism for the development of sporadic Alzheimer’s disease. Remarkably, we also found significant morphological differences between intra- and extracellular beta-amyloid and tau aggregates in human-induced pluripotent stem cell-derived cortical neurons, suggesting these neurons can only clear aggregates when small, and that larger aggregates stay inside the neurons. While majority of the beta-amyloid aggregates were cleared into the media, a greater portion of the tau aggregates remained intracellular. This size-dependent aggregate clearance was also shown to be conserved in vivo, using soaked and homogenized mouse and human post-mortem Alzheimer’s disease brain samples. As such, our results are proposing a previously unknown, size-dependent aggregate clearance mechanism, which can possibly explain the intracellular aggregation of tau and extracellular aggregation of beta-amyloid.
Characteristics of spontaneous regression of Merkel cell carcinoma: a retrospective analysis of patient and tumour features
Authors: Gamissans Marta , Muntaner-Virgili Clara , Penín Rosa-Maria , Marcoval Joaquim 
Published: December 2024

Abstract
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine neoplasia. Complete spontaneous regression (CSR) of MCC has been linked to good prognosis. We conducted a retrospective review of a single-centre cohort of patients with MCC to analyse the characteristics of patients and tumours that exhibited regression. The calculated incidence of CSR was 4.5% (n = 5/112). The median age at diagnosis was 69 years (interquartile range 31), tumours were primarily located on the head and neck, and the cohort exhibited a low rate of immunosuppression. After a median follow-up period of 4 years, none of the patients who underwent CSR showed recurrence or distant metastases. Merkel cell polyomavirus (MCPyV) positivity was associated with CSR (P = 0.045). There is limited understanding of the mechanisms underlying regression in MCC. However, biopsy-induced immune responses linked with host and tumour factors, such as age, immunosuppression and MCPyV positivity, may play an important role. More research in this field is crucial to improve our understanding of this rare phenomenon.
Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): an externally controlled study
Authors: Whalen John , Chandra Anita , Kracker Sven , Ehl Stephan , Seidel Markus G , Gulas Ioana , Dron Louis , Velummailum Russanthy , Nagamuthu Chenthila , Liu Sichen , Tutein Nolthenius Joanne , Maccari Maria Elena 
Published: December 2024

Abstract
Leniolisib, an oral, targeted phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, was well-tolerated and efficacious versus placebo in treating individuals with activated PI3Kδ syndrome (APDS), an ultra-rare inborn error of immunity (IEI), in a 12-week randomised controlled trial. However, longer-term comparative data versus standard of care are lacking. This externally controlled study compared the long-term effects of leniolisib on annual rate of respiratory tract infections and change in serum immunoglobulin M (IgM) levels versus current standard of care, using data from the leniolisib single-arm open-label extension study 2201E1 (NCT02859727) and the European Society for Immunodeficiencies (ESID) registry. The endpoints were chosen following feasibility assessment considering comparability and availability of data from both sources. Baseline characteristics between groups were balanced through inverse probability of treatment weighting. The leniolisib-treated group included 37 participants, with 62 and 49 participants in the control group for the respiratory tract infections and serum IgM analyses, respectively. Significant reductions in the annual rate of respiratory tract infections (rate ratio: 0.34; 95% confidence interval [CI]: 0.19, 0.59) and serum IgM levels (treatment effect: –1.09 g/L; 95% CI: –1.78, –0.39, P = 0.002) were observed in leniolisib-treated individuals versus standard of care. The results were consistent across all sensitivity analyses, regardless of censoring, baseline infection rate definition, missing data handling, or covariate selection. These novel data provide an extended comparison of leniolisib treatment versus standard of care, highlighting the potential for leniolisib to deliver long-term benefits by restoring immune system function and reducing infection rate, potentially reducing complications and treatment burden.
Paramagnetic monomer and diamagnetic polymer of 5-(1-adamantyl)-1,3-phenylene bis(tert-butyl nitroxide)
Authors: Ueno Shunya , Takeshi Shin-ichiro , Suzuki Shuichi , Ishida Takayuki 
Published: December 2024

Abstract
In the crystalline state of the title biradical each nitroxide group is located close to each other, to form a covalently bonded diamagnetic polymer having a head-to-tail (N-O)2 motif. The solid irreversibly turned paramagnetic above 365 K. ESR spectra on a PVC solid solution displayed a zero-field splitting pattern together with a half-field signal at room temperature. Density functional theory calculations support the interpretation of the magnetic ground states and a four-center two-electron bonding character. Coordination ability was also explored.
Stannylation of alkyl chlorides with stannylpotassium
Authors: Hiraoka Yuta , Nakamoto Masaaki , Tsushima Takumi , Yoshida Hiroto 
Published: December 2024

Abstract
A stannylpotassium reagent, generated in situ from a readily available silylstannane and t-BuOK, is demonstrated to react smoothly with an alkyl bromide to give an alkylstannane in high yield. The superior nucleophilicity of the stannylpotassium reagent is illustrated in the efficient stannylative substitution of less reactive alkyl chlorides. Mechanistic studies reveal that the reaction proceeds through an ionic, SN2-type pathway.
The risk of sodium overcorrections in severe hyponatremia and the utility of desmopressin: a large retrospective study
Authors: Lamarche Florence , Ammann Hélène , Dallaire Gabriel , Deslauriers Louis , Troyanov Stéphan 
Published: December 2024

ABSTRACT

Background
The suggested narrow rate of serum sodium (sNa) correction in hyponatremia can be difficult to respect, leading to overcorrections. Our ability to anticipate the rapidity of correction according to the mechanism of hyponatremia is uncertain. While desmopressin is often used to pause a rapid rise in sNa, its dose-related effect is also not well described. We studied the rate of hyponatremia overcorrections, its prediction and the utility of desmopressin in its management.

Methods
We retrospectively reviewed all cases of severe hyponatremia (sNa &lt;120 mmol/L) in a large university hospital that occurred over 10 years. We assessed investigations, causes and treatments. We compared all sNa separated by at least 8 h and calculated correction rates. Significant overcorrection rates were defined by any rise of sNa &gt;9 mmol/L per day sustained over at least 24 h.

Results
After exclusions, we found 355 episodes of severe hyponatremia. Low, appropriate and inappropriate antidiuretic hormone (ADH)-defined mechanisms accounted for 17%, 24% and 29% of etiologies, respectively, with the remaining 25% secondary to diuretics and 5% of uncertain causes. First urinary sodium and osmolality were consistent with the final diagnosis in 73%. Significant overcorrections were seen in 45% and were frequent in the setting of low ADH. Desmopressin was given in 82 episodes, more often as a rescue than a preventive measure, with the subsequent sNa dropping by ≥5 mmol/L by 12 h in eight instances. The dose of desmopressin (≥2 µg versus 1 µg) and a higher volume of intravenous free-water coadministration resulted in a clinically meaningful greater reduction in sNa in the following 12 h.

Conclusions
Overcorrections in severe hyponatremia are common, mainly when ADH is low. Initial urinary measurements anticipate this risk. Desmopressin effectively halted the rate of correction in a dose-dependent manner. Caution should be given when coadministrating water, which can significantly lower the sNa.
Impact of heart rate on eGFR decline in ischemic stroke patients
Authors: Lee Jiann-Der , Kuo Ya-Wen , Lee Chuan-Pin , Huang Yen-Chu , Lee Meng , Lee Tsong-Hai 
Published: December 2024

ABSTRACT

Background
Resting heart rate is a potent predictor of various renal outcomes. However, the decline rate of renal function in ischemic stroke patients is not well defined. We tested the association of heart rate with estimated eGFR decline and the composite renal outcomes in patients with recent ischemic stroke.

Methods
The data of 9366 patients with ischemic stroke with an eGFR of ≥30 mL/min/1.73 m2 were retrieved from the Chang Gung Research Database. Mean initial in-hospital heart rates were averaged and categorized into 10-beats-per-minute (bpm) increments. The outcomes were the annualized change in eGFR across the heart rate subgroups and composite renal outcomes, namely a ≥40% sustained decline in eGFR, end-stage renal disease, or renal death. Generalized estimating equation models were used to determine the annualized change in eGFR and Cox proportional hazards regression models were used to estimate the relative hazard of composite renal outcomes by referencing the subgroup with a heart rate of &lt;60 bpm.

Results
The annual eGFR decline in the patients with a mean heart rate of &lt;60, 60–69, 70–79, 80–89, and ≥90 bpm was 2.12, 2.49, 2.83, 3.35, and 3.90 mL/min/1.73 m2, respectively. Compared with the reference group, the adjusted hazard ratios for composite renal outcomes were 1.17 [95% confidence interval (CI), 0.89–1.53), 1.54 (95% CI, 1.19–2.00), 1.72 (95% CI, 1.30–2.28), and 1.84 (95% CI, 1.29–2.54] for the patients with a heart rate of 60–69, 70–79, 80–89, and ≥90 bpm, respectively. In the subgroup analysis, the associations between higher heart rate and both eGFR decline and composite renal outcomes were more evident and statistically significant in patients without atrial fibrillation.

Conclusions
A higher heart rate is associated with a faster rate of eGFR decline and an increased risk of composite renal outcomes after ischemic stroke, particularly in patients without atrial fibrillation. These results underscore the importance of heart rate monitoring and management in ischemic stroke patients in sinus rhythm to potentially mitigate renal function decline. Further studies are needed to explore this relationship in patients with atrial fibrillation and across different ethnic groups.
Top ten tips in managing ANCA vasculitis
Authors: Tan Min Hui , Jayne David 
Published: December 2024

ABSTRACT
Diagnosing and managing antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) remain a challenge for many clinicians, due to the complexity of the disease manifestations and its treatment. There has been a paradigm shift in ANCA vasculitis management, where treatment incorporates both emergency life- and organ-saving procedures and longer-term care to manage relapse and co-morbidity risk and the complications of organ damage. Here, we highlight 10 key tips for the management of ANCA-associated vasculitis based on current evidence and clinical experience. First, we advise making the diagnosis as early as possible, emphasizing the importance of using high-quality ANCA assays. Second, we recommend the use of glucocorticoids in combination with rituximab and/or cyclophosphamide as induction therapy. Third, plasma exchange should be considered in patients with severe renal impairment and diffuse alveolar haemorrhage. We advise the use of rapidly reducing glucocorticoid regimens and advocate consideration of avacopan early in the disease course. We recommend the use of rituximab as maintenance therapy and routine monitoring of kidney function, proteinuria, ANCA and immunoglobulin levels at baseline and during follow-up. The use of prophylactic antibiotics in susceptible patients and timely vaccination schedules is discussed. Rituximab is the preferred immune suppressive for treatment of relapse. Finally, we recommend switching treatment modalities in patients whose vasculitis is refractory to induction therapy and to consider plasma exchange in selected patients. These key tips aim to provide the necessary guidance to improve patient outcomes and reduce adverse events.
Upper normal serum magnesium is associated with a reduction in incident death from fatal heart failure, coronary heart disease and stroke in non-dialysis patients with CKD stages 4 and 5
Authors: Moyano-Peregrin Cayetana , Rodelo-Haad Cristian , Martín-Malo Alejandro , Muñoz-Castañeda Juan Rafael , Ojeda Raquel , Lopez-Lopez Isabel , Rodríguez Mariano , Pendon-Ruiz de Mier Mª Victoria , Santamaría Rafael , Soriano Sagrario 
Published: December 2024

ABSTRACT

Background
Serum magnesium disturbances are common in patients with cardiovascular disease (CVD). However, the well-established link between low serum magnesium and nutritional or inflammatory disorders has limited its consideration as a non-traditional risk factor for mortality. This study aims to elucidate the relationship between serum magnesium concentrations and mortality due to fatal heart failure (HF), coronary heart disease (CHD) and stroke in non-dialysis patients with chronic kidney disease (CKD) stages 4 and 5.

Methods
A cohort of 1271 non-dialysis patients with CKD stages 4 and 5 was followed from 2008 to 2018. Patients with prior major adverse cardiovascular events (MACE) were excluded. Serum magnesium levels were stratified into tertiles and the primary outcomes were incidence rates of fatal HF, CHD and stroke. Secondary outcomes included composite MACE and all-cause mortality. Hazard ratios (HRs) were calculated using multivariate Cox regression, adjusting for demographics, comorbidities and biochemical parameters. E-values were used to assess the robustness of the results.

Results
Over the 10-year follow-up, 186 patients died. Higher serum magnesium levels were significantly associated with reduced mortality risk from HF [HR 0.49 (95% CI 0.27–0.89) for T2; HR 0.31 (95% CI 0.16–0.60) for T3] compared with the lowest tertile. Similar trends were observed for CHD and stroke mortality. The incidence rate of MACE per 1000 person-years was reduced from 68.2 in tertile 1 to 26.2 in tertile 2 and 16.8 in tertile 3. Secondary endpoints, including all-cause mortality and composite MACE, followed trends similar to the primary outcomes.

Conclusions
Higher serum magnesium concentrations were associated with lower risks of death from fatal HF, CHD and stroke in non-dialysis patients with CKD stages 4 and 5.
A path forward: improving Internet routing security by enabling zones of trust
Authors: Clark David , Testart Cecilia , Luckie Matthew , claffy kc 
Published: December 2024

Abstract
Although Internet routing security best practices have recently seen auspicious increases in uptake, Internet Service Providers (ISPs) have limited incentives to deploy them. They are operationally complex and expensive to implement and provide little competitive advantage. The practices with significant uptake protect only against origin hijacks, leaving unresolved the more general threat of path hijacks. We propose a new approach to improved routing security that achieves four design goals: improved incentive alignment to implement best practices; protection against path hijacks; expanded scope of such protection to customers of those engaged in the practices; and reliance on existing capabilities rather than needing complex new software in every participating router. Our proposal leverages an existing coherent core of interconnected ISPs to create a zone of trust, a topological region that protects not only all networks in the region, but all directly attached customers of those networks. Customers benefit from choosing ISPs committed to the practices, and ISPs thus benefit from committing to the practices. We discuss the concept of a zone of trust as a new, more pragmatic approach to security that improves security in a region of the Internet, as opposed to striving for global deployment. We argue that the aspiration for global deployment is unrealistic, since the global Internet includes malicious actors. We compare our approach to other schemes and discuss how a related proposal, ASPA, could be used to increase the scope of protection our scheme achieves. We hope this proposal inspires discussion of how the industry can make practical, measurable progress against the threat of route hijacks in the short term by leveraging institutionalized cooperation rooted in transparency and accountability.
Chylothorax as an unusual manifestation of transthyretin cardiac amyloidosis: a case report
Authors: Pöschl Christina , Kratzer Theresa , Martinek Martin , Steringer-Mascherbauer Regina 
Published: December 2024

Abstract

Background
Amyloidosis is a multi-organ disease of emerging significance in the field of cardiology. Chylothorax, a specific form of pleural effusion characterized by lymphatic fluid accumulation in the pleural cavity, is an extremely rare manifestation of amyloidosis. Notably, only five cases of chylothorax related to cardiac amyloidosis have been reported worldwide, all in amyloid light chain (AL) amyloidosis. No cases have been documented in amyloid transthyretin (ATTR) amyloidosis. Furthermore, elevated levels of serum carbohydrate antigen (CA) 125 have been associated with a poor prognosis in patients with AL cardiac amyloidosis.

Case summary
We report the case of an 85-year-old Austrian man with pronounced left ventricular hypertrophy, monoclonal gammopathy, and a history of atrial fibrillation. Further examinations, including myocardial biopsy, confirmed the diagnosis of ATTR cardiac amyloidosis. A significant right-sided pleural effusion was also observed. Thoracocentesis diagnosed chylothorax, confirmed by lymphangiography. Elevated CA 125 levels were found in both serum and pleural fluid, with no other findings suspicious for malignancy. The patient underwent a short break in oral anticoagulation and received prophylactic low-molecular-weight heparin for myocardial biopsy, thoracocentesis, and lymphangiography. However, they died a few days later due to an embolic stroke.

Discussion
At this time, we can only speculate about the pathomechanism of chylothorax development in the context of amyloidosis. We recommend further investigation of similar cases to deepen understanding of the underlying causes and identify potential treatment strategies. Additionally, the utility of CA 125 as a prognostic marker in ATTR amyloidosis needs further investigation.