bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stress hyperglycemia ratio as an important predictive indicator for severe disturbance of consciousness and all-cause mortality in critically ill patients with cerebral infarction: a retrospective study using the MIMIC-IV database
Authors: Li Xiaosheng , Guo Li , Zhou Yuzhen , Yuan Churan , Yin Yong 
Published: January 2025

Abstract

Background
Stress hyperglycemia ratio (SHR) has been linked to prognosis of cerebrovascular diseases. Nevertheless, the association between SHR and severe disturbance of consciousness (DC) and mortality among patients with cerebral infarction remains explored. This study seeks to assess the predictive potential of SHR for severe DC and mortality among patients with cerebral infarction.

Methods
We identified individuals diagnosed with cerebral infarction within the MIMIC-IV database. We employed logistic regression to examine the correlation between the SHR index and the severity of patients' consciousness disturbance, as well as in-hospital mortality. Furthermore, we employed restricted cubic spline curves to explore potential non-linear relationships between the SHR index and outcome measures. To assess the predictive performance of the SHR index and admission blood sugar level on outcome indicators, we compared receiver operating characteristic (ROC) curves.

Results
A non-linear relationship existed between SHR and the risk of severe disturbance of consciousness, while there was a linear relationship with all-cause mortality. The AUC value for predicting severe disturbance of consciousness by the SHR index is 0.5419 (95% CI: 0.5188–0.5661). The AUC value for predicting in-hospital mortality based on the SHR index is 0.6264 (95% CI: 0.5881–0.6662). It is superior to single admission blood sugar level. In addition, SHR has an incremental impact on evaluating various diseases in predicting severe disturbance of consciousness and all-cause mortality in critically ill patients with cerebral infarction.

Conclusions
SHR is an important predictive indicator for severe disturbance of consciousness and all-cause mortality of patients with cerebral infarction.

Graphical Abstract
Extrapolation of cavitation and hydrodynamic pressure in lubricated contacts: a physics-informed neural network approach
Authors: Brumand-Poor Faras , Azanledji Freddy Kokou , Plückhahn Nils , Barlog Florian , Boden Lukas , Schmitz Katharina 
Published: January 2025

Abstract
A comprehensive understanding of the dynamics of tribological interactions is essential for enhancing efficiency and durability in a multitude of technical domains. Conventional experimental techniques in tribology are frequently costly and time-consuming. In contrast, elastohydrodynamic lubrication (EHL) simulation models present a viable alternative for calculating frictional forces in sealing contacts. These calculations are based on the hydrodynamics within the sealing contact, as defined by the Reynolds equation, the deformation of the seal, and the contact mechanics. However, a significant drawback of these simulations is the time-consuming calculation process. To overcome these experimental and computational limitations, machine learning algorithms offer a promising solution. Physics-informed machine learning (PIML) improves on traditional data-driven models by incorporating physical principles. In particular, physics-informed neural networks (PINNs) are as effective hybrid solvers that combine data-driven and physics-based methods to solve the partial differential equations that drive EHL simulations. By integrating physical laws into the parameter optimization of the neural network (NN), PINNs provide accurate and fast solutions. Thus, unlike traditional NNs, PINNs have the potential to make accurate predictions beyond the limited training domain. The objective of this study is to demonstrate the feasibility of spatial and temporal extrapolation of the PINN and to analyze its reliability, both with and without consideration of cavitation. Two test cases are employed to examine the pressure and cavitation distribution within a sealing contact that extends beyond the spatial and temporal training range. The findings indicate that PINNs can surmount the typical constraints associated with NNs in the extrapolation of solution spaces, which represents a notable advancement in terms of computational efficiency and model flexibility.
A probabilistic model-based approach to assess and minimize scaling in geothermal plants
Authors: Shoeibi Omrani Pejman , Poort Jonah , Barros Eduardo G. D. , de Zwart Hidde , Machado Cintia Gonçalves , Wasch Laura , Twerda Aris , Rijnaarts Huub H. M. , Shariat Torbaghan Shahab 
Published: January 2025

Abstract
Geothermal installations often face operational challenges related to scaling which can lead to loss in production, downtime, and an increase in operational costs. To accurately assess and minimize the risks associated with scaling, it is crucial to understand the interplay between geothermal brine composition, operating conditions, and pipe materials. The accuracy of scaling predictive models can be impacted by uncertainties in the brine composition, stemming from sub-optimal sampling of geothermal fluid, inhibitor addition, or measurement imprecision. These uncertainties can be further increased for fluid at extreme conditions especially high salinity and temperature. This paper describes a comprehensive method to determine operational control strategies to minimize the scaling considering brine composition uncertainties. The proposed modelling framework to demonstrate the optimization under uncertainty workflow consists of a multiphase flow solver coupled with a geochemistry model and an uncertainty quantification workflow to locally estimate the probability of precipitation potential, including its impact on the hydraulic efficiency of the geothermal plant by increasing the roughness and/or decreasing the diameter of the casings and pipelines. For plant operation optimization, a robust control problem is formulated with scenarios which are generated based on uncertainties in brine composition using an exhaustive search method. The modelling and optimization workflow was demonstrated in a geothermal case study dealing with barite and celestite scaling in a heat exchanger. The results showed the additional insights in the potential impact of brine composition uncertainties (aleatoric uncertainties) in scaling potential and precipitation location. Comparing the outcome of optimization problem for the deterministic and fluid composition uncertainties, a change of up to 2.5% in the temperature control settings was observed to achieve the optimal coefficient of performance.
hUC-MSC preserves erectile function by restoring mitochondrial mass of penile smooth muscle cells in a rat model of cavernous nerve injury via SIRT1/PGC-1a/TFAM signaling
Authors: Yang Mengbo , Chen Xinda , Zhang Ming , Zhang Xiaolin , Xiao Dongdong , Xu Huiming , Lu Mujun 
Published: January 2025

Abstract

Background
Cavernous nerve injury-induced erectile dysfunction (CNI-ED) is a common complication following radical prostatectomy and severely affects patients’ quality of life. The mitochondrial impairment in corpus cavernosum smooth muscle cells (CCSMCs) may be an important pathological mechanism of CNI-ED. Previous studies have shown that transplantation of human adipose derived stem cells (ADSC) can alleviate CNI-ED in a rat model. However, little is known about the effect of human umbilical cord mesenchymal stem cells (hUC-MSC) on CNI-ED. It remains unclear whether hUC-MSC can ameliorate mitochondrial damage in CCSMCs. In this study, we aimed to investigate the impacts of hUC-MSC on the mitochondrial mass and function of CCSMCs, as well as elucidate its underlying molecular mechanism.

Methods
The CNI-ED rat model was established by bilaterally crushing cavernous nerves. Subsequently, hUC-MSC were transplanted into the cavernosum and ADSC were injected as a positive control group. Erectile function evaluation and histological detection were performed 4 weeks after cell transplantation. In vitro, CCSMCs underwent hypoxia and were then co-cultured with ADSC or hUC-MSC using a transwell system. The mitochondrial mass and function, as well as signaling pathways, were investigated. To explore the role of the SIRT1/PGC-1α/TFAM pathway in regulating mitochondrial biogenesis of CCSMCs, we knocked down SIRT1 by siRNA.

Results
The administration of hUC-MSC significantly improved erectile function of CNI-ED rats and reduced the ratio of collagen to smooth muscle. Specifically, hUC-MSC treatment restored mitochondrial mass and function in CCSMCs injured by CNI or hypoxia, and inhibited the apoptosis of CCSMCs. Mechanistically, the application of hUC-MSC activated SIRT1/PGC-1α/TFAM pathway both in rat penile tissues and CCSMCs. In addition, knockdown of SIRT1 in CCSMCs abolished the protective effects of hUC-MSC on mitochondrial mass and function, while leading to an increase in cellular apoptosis.

Conclusions
hUC-MSC contribute to the recovery of erectile function in CNI-ED rats by restoring mitochondrial mass and function of CCSMCs through the SIRT1/PGC-1α/TFAM pathway. Our present study offers new insights into the role and molecular mechanisms of hUC-MSC in regulating mitochondrial homeostasis, thereby facilitating the restoration of the erectile function in CNI-ED.
The Sub 2-h Official Marathon is Possible: Developing a Drafting Strategy for a Historic Breakthrough in Sports
Authors: Fernandes G. D. , Laureano Gandur Nazir , Santos Dioser , Maldonado Victor 
Published: January 2025

Abstract

Background
Drafting for drag reduction is a tactic commonly employed by elite athletes of various sports. The strategy has been adopted by Kenyan runner Eliud Kipchoge on numerous marathon events in the past, including the 2018 and 2022 editions of the Berlin marathon (where Kipchoge set two official world records), as well as in two special attempts to break the 2 h mark for the distance, the Nike Breaking2 (2017) and the INEOS 1:59 Challenge (2019), where Kipchoge used an improved drafting formation to finish in 1:59:40, although that is not recognized as an official record.

Results
In this study, the drag of a realistic model of a male runner is calculated by computational fluid dynamics for a range of velocities. The formations employed in the past by Kipchoge, as well as alternative formations, are analyzed and systematically compared with respect to mechanical power. In a quest to show that running an official marathon in under 2 h is possible, the power analysis is extended to the pacers. We developed a simple drafting and pacing strategy that Kipchoge could have used to run the 2022 Berlin marathon in a surprising 1 h, 59 min and 48 s.

Conclusions
Elite marathon runners can make better use of the pacers to experience reduced drag in races. The associated energy reduction makes it possible to run faster, finishing the race in less time. Using a better drafting strategy and a positive splitting pacing strategy, Kenyan runner Eliud Kipchoge could have broken the sub 2 h barrier in both the 2018 and 2022 editions of Berlin Marathon.
Acute decompensated right heart failure potentially triggered by multiple factors including pulmonary vasodilator removal during plasma exchange: a case report
Authors: Toki Takayuki , Mizunoya Kazuyuki , Itabashi Misa , Nishikawa Naoki , Hoshino Koji , Saito Hitoshi , Morimoto Yuji 
Published: January 2025

Abstract

Background
Plasma exchange (PE) removes high-molecular-weight substances and is sometimes used for antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with alveolar hemorrhage. Hypotension during PE is rare, except in allergic cases. We report a case of shock likely caused by increased pulmonary vascular resistance (PVR) during PE.

Case presentation
A 66-year-old man with pulmonary hypertension (PH) and glomerulonephritis was admitted with dyspnea. He had discontinued sildenafil prior to admission. Alveolar hemorrhage associated with AAV was suspected, and PE was performed. Soon after, he developed circulatory failure and hyperlactatemia. Echocardiography revealed right ventricular dilation, suggesting increased PVR. Inhaled nitric oxide (iNO) was administered, rapidly improving hyperlactatemia and oxygenation. The shock observed during PE was attributed to multiple factors, including the potential removal of sildenafil, which may have led to an increase in PVR.

Conclusions
The shock was attributable to acute right heart failure caused by an exacerbation of PH, possibly due to sildenafil removal via PE, although other contributing factors could not be excluded.
Hepatoprotective potential of Chrysin in a rat model of isoniazid- and rifampicin-induced hepatic injury: suppression of matrix metalloproteinase and transforming growth factor β
Authors: Mandlik Deepa , Tokey Akhilesh , Lokhande Rohit , Dagadu Yash , Choudhary Heena , Mandlik Satish 
Published: January 2025

Abstract

Background
The ability of Chrysin (CHY) to scavenge free radicals has been widely explored. The scope of the research was to show that CHY protects the rat liver against damage caused by the drugs isoniazid (INH) and rifampicin (RFM).

Results
Rats were divided into 6 groups, each of which had six rats. Isoniazid (100 mg/kg, p.o.) and rifampicin (100 mg/kg, p.o.) were administered to Group II to VI rats for 21 days; this caused hepatocellular damage. CHY was administered in the dose of 50, 75, and 100 mg/kg, p.o. body weight to Group III to V rats before administration of INH + RFM. In this study, Group VI Silymarin (100 mg/kg, p.o.) functioned as the standard drug. The blood was drawn as the study was done, and tests for oxidative stress indicators, haematological parameters, biochemical parameters, and pro-inflammatory cytokines were performed. The liver samples were subjected to histopathology. The administration of CHY (50, 75, and 100 mg/kg) restored serum biochemical, haematological, proteins, and lipid parameters. Due to the administration of CHY, the levels of superoxide dismutase (SOD), glutathione oxidase (GSH), myeloperoxidase (MPO) and catalase (CAT) were also restored. The inflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), transforming growth factor-β (TGF-β), malondialdehyde (MDA), myeloperoxidase (MPO) and nitric oxide (NO) levels were found to be decreased. The alterations in the biochemical parameters were reinforced by histological analysis of liver tissue.

Conclusions
It is concluded that the CHY protects against INH + RFM-induced oxidative liver injury in rats.

Graphical abstract
Retreatment with immune checkpoint inhibitors (ICIs) for patients with advanced gastric cancer: A retrospective, real-world study.
Authors: Jia Yong-Xu , Liu Yihan , Han Hui-Qiong , Gao Ya-Ping , Qin Yanru 
Published: January 2025

343

Background:
Immunotherapy combined with chemotherapy has become the standard first-line treatment for advanced gastric cancer and is recommended by multiple guidelines and consensuses. After the first line immunotherapy, there is still controversy over whether immune inhibitors can continue to be used across lines after progression.
Methods:
This is a single-center, retrospective, observational, real-world study. We collected clinical information of patients with advanced gastric cancer hospitalized at the First Affiliated Hospital of Zhengzhou University from January 2018 to July 2024. All patients received combination therapy with ICIs inhibitors for at least 2 cycles in the first-line and at least 2 cycles of ICI inhibitor-based therapy in the second-line after first-line progression. The efficacy and safety of treatment were evaluated, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), the progression pattern of retreatment with immune checkpoint inhibitor, grade 3-5 treatment-related adverse events (TRAEs), and immune-related adverse events (irAEs). Cox regression model was used to investigate the influence of multiple factors on survival.
Results:
We included 217 patients with a median age of 59.0 (18-84) years, of which 70.0% were male. The median OS and PFS were 9.8 (95% CI 8.8-10.8) months and 4.6 (95% CI 4.0-5.3) months. The ORR and DCR were 22.7% (95% CI 17.1-29.0) and 56.2% (95% CI 49.0-63.1). For the second-line treatment regimens, there were 87 (40.1%) patients and 130 (59.9%) patients received immunotherapy combined with chemotherapy (I+C) and immunotherapy combined with chemotherapy and anti-angiogenic drugs(I+C+A) respectively. The median OS was 9.3 (95% CI 8.5-10.1) months and 11.5 (95% CI 9.3-13.7) months, p=0.032. The median PFS was 4.2 (95% CI 3.1-5.3) months and 5.2 (95% CI 4.3-6.1) months, p=0.082. Cox regression model analysis showed that ECOG 0-1, PFS≥6 months in the first-line treatment, second-line regimen (I+C+A), and second-line medication > 3 cycles were independent prognostic factors for OS in the second-line treatment. The incidence of grade ≥3 TRAEs was 20.7%, and the incidence of irAEs was 6.5%. No treatment-related deaths occurred.
Conclusions:
This real-world study results showed that retreatment with immune checkpoint inhibitors had promising clinical benefit for patients with advanced gastric cancer and manageable safety.

Efficacy of different groups.

n
mOS（m）
mPFS（m）
ORR（%）
DCR（%）

ITT
217
9.8
4.6
22.7
56.2

ECOG

0-1

180
9.8
4.7
19.5
56.8

2

37
8.6
4.0
38.2
52.9

1-Line PFS

＜3m

61
5.5
2.2
1.7
17.2

≥3m

156
11.7
6.0
31.0
71.7

＜6m

136
7.4
3.2
2.4
38.7

≥6m

81
15.1
8.0
54.4
83.5

Second-line treatment

I+C

87
9.3
4.2
16.9
54.2

I+C+A

130
11.5
5.2
26.7
57.5

Second-line treatment cycle

≤3

97
7.4
2.9
4.8
31.0

＞3

120
13.1
6.2
35.3
73.9
Endocrine Alterations in Patients With Pachydermoperiostosis
Authors: Stelmachowska-Banaś Maria , Barry Sayka , Angurala Ishita , Rice Tom , Magid Kesson , Carreira Ana , Rai Ashutosh , Evans Amy , Bollington Mark , Kaur Vaishali , Singhmar Shallu , Silaghi Cristina Alina , Mandisodza Kudakwashe , McGregor Alan , Sahoo Jayaprakash , Gupta Rahul , Behera Kishore Kumar , Roy Ayan , Carr Ian M , Loughrey Paul Benjamin , Dutta Pinaki , Korbonits Márta 
Published: January 2025

Abstract

Context
Pachydermoperiostosis (primary hypertrophic osteoarthropathy, PHO), usually due to biallelic loss of function variants in HPGD and SLCO2A1, has some features overlapping with acromegaly and is often referred to endocrinologists. A detailed endocrine assessment is not available for these patients.

Objective
To assess the genetic and endocrine characteristics of patients with PHO referred to endocrine centers with a possible diagnosis of acromegaly.

Methods
Seventeen patients from 14 families in which acromegaly was excluded based on lack of elevated insulin-like growth factor (IGF)-1 levels and/or growth hormone suppression on an oral glucose tolerance test were assessed for HPGD and SLCO2A1 variants.

Results
Age at diagnosis was 26.2 ± 9.0 years (mean ± SD, range 9-43). Digital clubbing was present in all patients. Periostosis (94%), arthralgia (88%), periarticular edema (77%), pachydermia (82%), and coarsened facial features resembling acromegaly (71%) were present in the vast majority of the patients, while eyelash trichomegaly, blepharoptosis, high-arched palate, gingival hypertrophy, gastrointestinal symptoms, and marfanoid habitus were seen in some. Nine patients (53%) had low IGF-1 levels; the rest of the patients had IGF-1 levels in the lowest quartile of the reference range. Estradiol concentration was increased above the normal range in 8 male patients (62%) with normal testosterone and prolactin levels. Biallelic HPGD (2/14 kindreds) or SLCO2A1 (8 novel) variants (12/14 kindreds) were found. Two patients had no identifiable pathogenic/likely pathogenic variant in HPGD or SLCO2A1. Their phenotype was not different from the other patients.

Conclusion
We establish that low IGF-1 and elevated estradiol levels are frequent features of PHO. Nine novel and 5 known pathogenic/likely pathogenic genetic variants were identified.
O-06 CUSHING’S SYNDROME DUE TO BILATERAL IMMUNHISTOCHEMICALLY-PROVEN ACTH POSITIVE ADRENAL NEOPLASMS
Authors: Ekşi Haydardedeoğlu Filiz , Bağır Gülay Şimşek , Kırbıyık Özgür , Emrah Koçer Nazım , Ertörer Melek Eda 
Published: January 2025

Abstract

Introduction
Ectopic ACTH secretion is a rare cause of endogenous hypercortisolism. Herein, a case of Cushing’s syndrome due to bilateral immunhistochemically-proven ACTH positive adrenal neoplasms is presented.

Clinical Case
A 60 year old women was admitted with acute-onset severe hypokalemia and hyperglycemia. She had severe metabolic alkalosis and her serum K levels kept being below 1.5 mmol/L, if left untreated. Physical examination demonstrated facial and upper body flushing, but was otherwise normal. Laboratory analyses were; early morning plasma ACTH: 211 pg/ml, early morning serum cortisol: 88.9 mcg/dl, late night serum cortisol: 58.8 mcg/dl, late night plasma ACTH:42.3 pg/ml, total testosterone: 1.79 ng/ml (0.120-0.350), DHEAS: 377.8 mcg/dl (29.7-182.2), 24 H urine free cortisol (UFC): 6696 mcg/24 h (urinary volume:2.7L), plazma aldosterone: 1.43 ng/dl, PRA&lt;0.1 ng/ml/saat, 17-OH-progesterone: 2.91 ng/ml, calcitonin &lt;2.0 pg/ml. Relying on rapid-onset of severe findings and very high UFC, our prediagnosis was Ectopic ACTH Syndrome. Thorax CT, 18-FDG-PET and Ga-68-PET scans did not exhibit any source. Abdominal CT scan revealed diffuse enlargement of both adrenal glands. Then Desmopressin test was performed and demonstrated central gradient (Table 1). However, pituitary MRI demonstrated no lesion, but thinning of the global gland. Accordingly inferior petrosal sinus sampling (IPSS) was compatible with ectopic ACTH syndrome (Table 2). Due to life-threatening hypercortisolemia of unknown origin, a decision was made in favor of bilateral adrenalectomy. Fluconazole 2x200mg/day iv was started, and after 48 hours, serum cortisol dropped significantly. The operation was performed safely, the patient’s general condition and serum potassium improved rapidly. Pathological specimen was reported as bilateral adrenocortical oncocytic neoplasms, and Ki-67 index was &lt;1%. Immunohistochemistry (IHC) showed strong staining for ACTH in both lesions (Figure).

Conclusion
Although very rare, adrenals should be kept in mind as a source of ectopic ACTH syndrome.Figure:Immunohistochemical (IHC) staining demonstrating ACTH-secreting adrenal tumors (original magnification x100) Table 1:Plasma ACTH levels following 10 mcg desmopressin given intravenously Table 2:Plasma ACTH levels during Inferior Petrosal Sinus Sampling test performed with desmopressin