bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-resolution and highly accelerated MRI T2 mapping as a tool to characterise renal tumour subtypes and grades
Authors: Horvat-Menih Ines , Li Hao , Priest Andrew N. , Li Shaohang , Gill Andrew B. , Mendichovszky Iosif A. , Francis Susan T. , Warren Anne Y. , O’Carrigan Brent , Welsh Sarah J. , Jones James O. , Riddick Antony C. P. , Armitage James N. , Mitchell Thomas J. , Stewart Grant D. , Gallagher Ferdia A. 
Published: July 2024

Abstract
Background
Clinical imaging tools to probe aggressiveness of renal masses are lacking, and T2-weighted imaging as an integral part of magnetic resonance imaging protocol only provides qualitative information. We developed high-resolution and accelerated T2 mapping methods based on echo merging and using k-t undersampling and reduced flip angles (TEMPURA) and tested their potential to quantify differences between renal tumour subtypes and grades.

Methods
Twenty-four patients with treatment-naïve renal tumours were imaged: seven renal oncocytomas (RO); one eosinophilic/oncocytic renal cell carcinoma; two chromophobe RCCs (chRCC); three papillary RCCs (pRCC); and twelve clear cell RCCs (ccRCC). Median, kurtosis, and skewness of T2 were quantified in tumours and in the normal-adjacent kidney cortex and were compared across renal tumour subtypes and between ccRCC grades.

Results
High-resolution TEMPURA depicted the tumour structure at improved resolution compared to conventional T2-weighted imaging. The lowest median T2 values were present in pRCC (high-resolution, 51 ms; accelerated, 45 ms), which was significantly lower than RO (high-resolution; accelerated, p = 0.012) and ccRCC (high-resolution, p = 0.019; accelerated, p = 0.008). ROs showed the lowest kurtosis (high-resolution, 3.4; accelerated, 4.0), suggestive of low intratumoural heterogeneity. Lower T2 values were observed in higher compared to lower grade ccRCCs (grades 2, 3 and 4 on high-resolution, 209 ms, 151 ms, and 106 ms; on accelerated, 172 ms, 160 ms, and 102 ms, respectively), with accelerated TEMPURA showing statistical significance in comparison (p = 0.037).

Conclusions
Both high-resolution and accelerated TEMPURA showed marked potential to quantify differences across renal tumour subtypes and between ccRCC grades.

Trial registration
ClinicalTrials.gov, NCT03741426. Registered on 13 November 2018.

Relevance statement
The newly developed T2 mapping methods have improved resolution, shorter acquisition times, and promising quantifiable readouts to characterise incidental renal masses.

Graphical Abstract
The evolving landscape of publishing in human reproduction: an analysis of scientometric data, open-access publishing, and article processing charges
Authors: Uzun Hakki , Akça Görkem , Sönmez Berat , Orman Erdem , Kaçan Yakup , Dil Eyüp 
Published: July 2024

Abstract
Background
This bibliometric study aims to examine the associations of journals in the field of human reproduction with their access types and article processing charges to evaluate the evolving landscape of publishing in human reproduction.

Methods
The primary databases, including Clarivate Analytics Master Journal List, Scopus®, PubMed, and Directory of Open Access Journals, were scrutinized to identify pertinent journals within the realm of human reproduction, utilizing keywords such as reproductive, reproduction, fertility, and infertility. Journals were excluded if they were not actively publishing in English or primarily focused on reproductive health, men’s health, sexual medicine, embryogenesis, developmental biology, or veterinary medicine concerning animal reproduction. A thorough characterization of the journals was conducted, followed by a comparative analysis of citation metrics and article processing charges across various access models.

Results
Forty-one journals were included into the study. A significant increase in the proportion of gold and diamond open-access journals was observed, rising from 42% (13 out of 31) to 53.6% (22 out of 41) by 2023. Hybrid journals demonstrated superior citation metrics compared to diamond open-access journals. For hybrid journals, a statistically significant, moderately positive correlation was found between article processing charges and CiteScore (rs (27) = 0.515, p < .024). Conversely, no correlation was observed between article processing charges and CiteScore for gold open-access journals (rs (27) = 0.445, p = 0.147). The mean article processing charges for all hybrid and gold open-access journals were calculated as US $3032.88 ± 1108.514 (312 to 4430). Specifically, the mean article processing charges for hybrid journals (US $3617.4 ± 610.19) were significantly higher than those for gold open-access journals (US $1916.82 ± 988.32), with a difference of 1700.658 (95% CI: 1124.861–2276.455), t (30) = 6.032, and p < .0005.

Conclusion
Hybrid journals in the field of human reproduction carry fees nearly twice as high as those of gold open-access journals. The charging policies of gold open-access journals, which are not contigent upon citation metrics, emphasize the importance of caution for both authors and funders.
Tafamidis therapy in transthyretin amyloid cardiomyopathy: a narrative review from clinical trials and real-world evidence
Authors: Ogieuhi Ikponmwosa Jude , Ugiomoh Oshomoh Mark-Anthony , Muzofa Kudzaishe , Callender Kristen , Ayodeji Johnson David , Nnekachi Nnokam Prayer , Thiyagarajan Barkavi , Uduigwome Emmanuel Obokhai , Kapoor Abhay , Odoeke Moses Chukwuebuka , Mohamed Reem Gamaleldin Hassan , Idahor Courage 
Published: July 2024

Abstract
Background
Amyloidosis is a heterogeneous group of disorders caused by the extracellular deposition of insoluble misfolded proteins, leading to end-organ damage. Transthyretin amyloid cardiomyopathy (ATTR-CM) is a subtype in which a protein known as transthyretin accumulates within the heart tissue, progressively resulting in restrictive cardiomyopathy and heart failure. Due to the progressive nature of ATTR-CM, clinical management requires efficacious regimens to manage the debilitating condition and Tafamidis shows promising results in this regard.

Main body
ATTR-CM poses a significant challenge due to its nature and limited therapeutic options. Tafamidis is a novel therapy designed to stabilize the transthyretin tetramers, inhibiting the formation of amyloid fibrils. It has emerged as a promising treatment and the only FDA-approved drug for ATTR-CM. Tafamidis' role in slowing disease progression and improving outcomes in patients with ATTR-CM has been demonstrated in the major randomized control trial ATTR-ACT with promising open-label extension studies, some still ongoing. Additionally, real-world evidence supports its use in clinical practice, showing its role in reducing morbidity and mortality associated with this condition. Clinical evidence shows its efficacy in improving symptoms and cardiac function in patients. Case studies also reveal significant benefits to patients like reducing myocardial damage, reversal of atrial fibrillation, and resolution of heart failure symptoms. Real-world outcomes and clinical trials show a consistent reduction in amyloid deposition, cardiovascular-related hospitalizations, and all-cause mortality with Tafamidis therapy.

Conclusion
Tafamidis is an essential component of the treatment of ATTR-CM and this narrative review synthesizes the current evidence regarding safety, efficacy, and utilization in real practice. While it shows promising effects, its effectiveness may also vary and high cost precludes real-world large-scale studies. Overall, Tafamidis emerges as a valuable therapeutic option for managing ATTR-CM.
Analytical quality by design (AQbD) based optimization of RP-UPLC method for determination of nivolumab and relatlimab in bulk and pharmaceutical dosage forms
Authors: Nuli Mohana Vamsi , Seemaladinne Ramanjaneyulu , Tallam Anil Kumar 
Published: July 2024

Abstract
Background
The Analytical Quality by Design (AQbD) methodology extends the application of Quality by Design (QbD) principles to the management of the analytical procedure life cycle, encompassing method creation, optimization, validation, and continuous improvement. AQbD assists in creating analytical procedures that are robust, reliable, precise, and cost-efficient. Opdualag™ is a combination of Nivolumab and Relatlimab, which are antibodies that block programmed death receptor-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) receptors, used to treat advanced melanoma. This work aims to develop and validate a reversed-phase ultra-performance liquid chromatography (RP-UPLC) method using AQbD principles to determine NLB and RTB in pharmaceutical products.

Results
A central composite design (CCD) comprising three factors arranged in five distinct levels was implemented via Design-expert® software to optimize the chromatographic conditions. A mathematical model was constructed and the effects of three independent factors namely flow rate (X1), percentage of methanol in the mobile phase (X2), and temperature (X3) on responses including retention time (Y1–2), resolution factor (Y3), theoretical plates (Y4–5), and tailing factor (Y6–7) were investigated. The software determined the optimal chromatographic conditions for the separation of NLB and RTB, which were as follows: 32.80% methanol in the mobile phase, 0.272 mL/min flow rate, 29.42 °C column temperature, and 260 nm UV detection. The retention time for NLB and RTB were 1.46 and 1.88 min, respectively. The method exhibited linearity across the concentration ranges of 4–24 µg/mL for RTB and 12–72 µg/mL for NLB. The limits of detection (LOD) and limit of quantification (LOQ) for NLB and RTB, respectively, were 0.89 µg/mL, 2.69 µg/mL and 0.15 µg/mL and 0.46 µg/mL. The percentage relative standard deviation (%RSD) of intraday and interday precision for NLB and RTB was below 2. The recovery percentages for NLB and RTB were determined to be 99.57–100.43% and 99.59–100.61%, respectively. Both drugs were found to be susceptible to oxidative and photolytic degradation in forced degradation studies.

Conclusions
Employing the AQbD-based methodology, a straightforward, fast, accurate, precise, specific, and stability-indicating RP-UPLC method has been established for the quantitative analysis of NLB and its RTB in pharmaceutical formulations.
Predictive role of platelets to lymphocytes ratio and neutrophil to lymphocytes ratio in COPD exacerbation
Authors: Fayiad Hussien , Amer Ahmed Mohamed 
Published: July 2024

Abstract
Background
The hallmark of COPD is the progressive destruction of the lung parenchyma, which is frequently brought on by the body's inflammatory reaction to external stimuli (such as smoking cigarettes or pollution). According to reports, the peripheral blood's essential immune-related cell populations' absolute counts and ratios can accurately represent chronic inflammatory diseases. Complex interactions between immune-related cells, such as lymphocytes and neutrophils, are involved in inflammation, which can cause irreversible damage and loss of respiratory tissue. The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), two hematological indicators of inflammation, have been studied in a variety of disease states, including solid tumors, systemic lupus erythematosus, coronary artery disease, retinal artery occlusion, chronic kidney disease, and stable COPD.

Aim
Correlation between NLR and PLR and outcome of COPD exacerbation.

Materials and methods
This cross-sectional study included 80 patients with COPD exacerbation who visited the outpatient clinic or were admitted to the Chest Department. CRP and calculation of NLR and PLR within 24 h from admission and 1 month after discharge were obtained to identify the prognostic value of NLR and PLR for the exacerbation, hospitalization, mechanical ventilation, and mortality in patients with COPD.

Results
During COPD exacerbation PLR, NLR showed a statistically significant correlation with the need for hospitalization with a p value < 0.001. As regards correlation with mortality NLR was statistically significant with a p value of 0.006 while PLR showed a non-significant p value of 0.077. PLR and NLR were correlated with CRP as an inflammatory marker and both were statistically significant with p value 0.004 and < 0.001 respectively. During exacerbation, PLR and NLR were correlated with the need for mechanical ventilation and the results were statistically significant with p value < 0.001. PLR and NLR showed a significant increase during exacerbation compared to stable COPD patients 1 month after discharge with p value of < 0.001.

Conclusion
PLR and NLR are simple tests that could be used to predict the severity of COPD exacerbation and the need for hospitalization, MV, and mortality prediction.
Risk of Type 2 Diabetes, MASLD and Cardiovascular Disease in People Living With Polycystic Ovary Syndrome
Authors: Henney Alex E , Gillespiec Conor S , Lai Jonathan Y M , Schofield Pieta , Riley David R , Caleyachetty Rishi , Barber Thomas M , Miras Alexander D , Dobbie Laurence J , Hughes David M , Alam Uazman , Hydes Theresa J , Cuthbertson Daniel J 
Published: July 2024

Abstract

Background
Polycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes that may differ according to PCOS phenotype.

Methods
Using UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction associated steatotic liver disease, cardiovascular disease (CVD), hormone-dependent cancers, and dementia between PCOS participants and age- and body mass index-matched controls. We also compared multiorgan (liver, cardiac, and brain) magnetic resonance imaging (MRI) data and examined the impact of PCOS phenotype (hyperandrogenic and normoandrogenic) on these outcomes.

Results
We included 1008 women with PCOS (defined by diagnostic codes, self-reported diagnoses, or clinical/biochemical features of hyperandrogenism and a/oligoCmenorrhoea) and 5017 matched controls (5:1 ratio); median age, 61 years, body mass index, 28.4 kg/m². Adjusted Cox proportional hazard modeling demonstrated PCOS participants had greater incident T2D [hazard ratio (HR) 1.47; 95% confidence interval (CI), 1.11-1.95] and all-cause CVD (1.76; 1.35-2.30). No between-group differences existed for cancers or dementia. Liver MRI confirmed more PCOS participants had hepatic steatosis (proton density fat fraction &gt;5.5%: 35.9 vs 23.9%; P = .02) and higher fibroinflammation (corrected T1 721.4 vs 701.5 ms; P = &lt;.01) vs controls. No between-group difference existed for cardiac (biventricular/atrial structure and function) or brain (grey and white matter volumes) imaging. Normoandrogenic (but not hyperandrogenic) PCOS participants had greater incident all-cause CVD (1.82; 1.29-2.56) while hyperandrogenic (but not normoandrogenic) PCOS participants were more likely to have hepatic steatosis (8.96 vs 6.04 vs 5.23%; P = .03) with greater fibroinflammation (776.3 vs 707.7 vs 701.9 ms; P=&lt;.01).

Conclusion
Cardiometabolic disease may be increased in PCOS patients with a disease phenotype-specific pattern.
Nongenomic ERα-AMPK Signaling Regulates Sex-Dependent Bcrp Transport Activity at the Blood-Brain Barrier
Authors: Banks David B , Lierz Sydney L , Cannon Ronald E , Korach Kenneth S 
Published: July 2024

Abstract
The blood-brain barrier (BBB) is an extensive capillary network that protects the brain from environmental and metabolic toxins while limiting drug delivery to the central nervous system (CNS). The ATP-binding cassette transporter breast cancer resistance protein (Bcrp) reduces drug delivery across the BBB by actively transporting its clinical substrates back into peripheral circulation before their entry into the CNS compartment. 17β-Estradiol (E2)-elicited changes in Bcrp transport activity and expression have been documented previously. We report a novel signaling mechanism by which E2 decreases Bcrp transport activity in mouse brain capillaries via rapid nongenomic signaling through estrogen receptor α. We extended this finding to investigate the effects of different endocrine-disrupting compounds (EDCs) and selective estrogen receptor modulators (SERMs) on Bcrp transport function. We also demonstrate sex-dependent expression of Bcrp and E2-sensitive Bcrp transport activity at the BBB ex vivo. This work establishes an explanted tissue-based model by which to interrogate EDCs and SERMs as modulators of nongenomic estrogenic signaling with implications for sex and hormonal regulation of therapeutic delivery into the CNS.
Efficacy and Safety of Long-term Ketogenic Diet Therapy in a Patient With Type 1 Diabetes
Authors: Koutnik Andrew P , Klein Samuel , Robinson Austin T , Watso Joseph C 
Published: July 2024

Abstract
Fewer than 1% of patients with type 1 diabetes achieve normal glycemic control (glycated hemoglobin [HbA1c] &lt; 5.7%/ &lt; 39 mmol/mol). Additionally, exogenous insulin administration often causes “iatrogenic hyperinsulinemia,” leading to whole-body insulin resistance and increased risk of cardiovascular complications. We present data on the clinical efficacy and safety of a long-term (10-year) ketogenic diet (≤50 g carbohydrates/day) therapy in a patient with type 1 diabetes. The use of a ketogenic diet resulted in successful glycemic control, assessed by HbA1c (5.5%; 36.6 mmol/mol), continuous glucose monitoring median glucose (98 mg/dL; 5.4 mmol/L), and glucose time-in-range of 70 to 180 mg/dL (90%) without acute glycemic complications. In conjunction, there was a 43% decrease in daily insulin requirements. Low-density lipoprotein cholesterol increased, whereas small-dense low-density lipoprotein was in the normal range (&lt;90 nmol/L). No adverse effects were observed on thyroid function, kidney function, or bone mineral density. This case report demonstrates that a long-term ketogenic diet in a person with type 1 diabetes has considerable therapeutic benefits.
Impact of Frailty on Surgical Outcomes of Patients With Cushing Disease Using the Multicenter Registry of Adenomas of the Pituitary and Related Disorders Registry
Authors: Findlay Matthew C. , Rennert Robert C. , Lucke-Wold Brandon , Couldwell William T. , Evans James J. , Collopy Sarah , Kim Won , Delery William , Pacione Donato R. , Kim Albert H. , Silverstein Julie M. , Kanga Mridu , Chicoine Michael R. , Gardner Paul A. , Valappil Benita , Abdallah Hussein , Sarris Christina E. , Hendricks Benjamin K. , Torok Ildiko E. , Low Trevor M. , Crocker Tomiko A. , Yuen Kevin C. J. , Vigo Vera , Fernandez-Miranda Juan C. , Kshettry Varun R. , Little Andrew S. , Karsy Michael 
Published: July 2024

BACKGROUND AND OBJECTIVES:
Despite growing interest in how patient frailty affects outcomes (eg, in neuro-oncology), its role after transsphenoidal surgery for Cushing disease (CD) remains unclear. We evaluated the effect of frailty on CD outcomes using the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) data set from a collaboration of US academic pituitary centers.

METHODS:
Data on consecutive surgically treated patients with CD (2011-2023) were compiled using the 11-factor modified frailty index. Patients were classified as fit (score, 0-1), managing well (score, 2-3), and mildly frail (score, 4-5). Univariable and multivariable analyses were conducted to examine outcomes.

RESULTS:
Data were analyzed for 318 patients (193 fit, 113 managing well, 12 mildly frail). Compared with fit and managing well patients, mildly frail patients were older (mean ± SD 39.7 ± 14.2 and 48.9 ± 12.2 vs 49.4 ± 8.9 years, P < .001) but did not different by sex, race, and other factors. They had significantly longer hospitalizations (3.7 ± 2.0 and 4.5 ± 3.5 vs 5.3 ± 3.5 days, P = .02), even after multivariable analysis (β = 1.01, P = .007) adjusted for known predictors of prolonged hospitalization (age, Knosp grade, surgeon experience, American Society of Anesthesiologists grade, complications, frailty). Patients with mild frailty were more commonly discharged to skilled nursing facilities (0.5% [1/192] and 4.5% [5/112] vs 25% [3/12], P < .001). Most patients underwent gross total resection (84.4% [163/193] and 79.6% [90/113] vs 83% [10/12]). No difference in overall complications was observed; however, venous thromboembolism was more common in mildly frail (8%, 1/12) than in fit (0.5%, 1/193) and managing well (2.7%, 3/113) patients (P = .04). No difference was found in 90-day readmission rates.

CONCLUSION:
These results demonstrate that mild frailty predicts CD surgical outcomes and may inform preoperative risk stratification. Frailty-influenced outcomes other than age and tumor characteristics may be useful for prognostication. Future studies can help identify strategies to reduce disease burden for frail patients with hypercortisolemia.
Delay in the Diagnosis of Pediatric Brain Tumors in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis
Authors: Irshad Hammad Atif , Shariq Syeda Fatima , Khan Muhammad Ali Akbar , Shaikh Taha , Kakar Wasila Gul , Shakir Muhammad , Hankinson Todd C. , Enam Syed Ather 
Published: July 2024

BACKGROUND AND OBJECTIVES:
Vague symptoms and a lack of pathognomonic features hinder the timely diagnosis of pediatric brain tumors (PBTs). However, patients in low- and middle-income countries (LMICs) must also bear the brunt of a multitude of additional factors contributing to diagnostic delays and subsequently affecting survival. Therefore, this study aims to assess these factors and quantify the durations associated with diagnostic delays for PBTs in LMICs.

METHODS:
A systematic review of extant literature regarding children from LMICs diagnosed with brain tumors was conducted. Articles published before June 2023 were identified using PubMed, Google Scholar, Scopus, Embase, Cumulative Index to Nursing and Allied Health Literature, and Web of Science. A meta-analysis was conducted using a random-effects model through R Statistical Software. Quality was assessed using the Newcastle Ottawa Scale.

RESULTS:
A total of 40 studies including 2483 patients with PBT from 21 LMICs were identified. Overall, nonspecific symptoms (62.5%) and socioeconomic status (45.0%) were the most frequently reported factors contributing to diagnostic delays. Potential sources of patient-associated delay included lack of parental awareness (45.0%) and financial constraints (42.5%). Factors contributing to health care system delays included misdiagnoses (42.5%) and improper referrals (32.5%). A pooled mean prediagnostic symptomatic interval was calculated to be 230.77 days (127.58-333.96), the patient-associated delay was 146.02 days (16.47-275.57), and the health care system delay was 225.05 days (−64.79 to 514.89).

CONCLUSION:
A multitude of factors contribute to diagnostic delays in LMICs. The disproportionate effect of these factors is demonstrated by the long interval between symptom onset and the definitive diagnosis of PBTs in LMICs, when compared with high-income countries. While evidence-based policy recommendations may improve the pace of diagnosis, policy makers will need to be cognizant of the unique challenges patients and health care systems face in LMICs.