bluuebunny/crossref_metadata_2025_split huggingface dataset:
scMNMF: a novel method for single-cell multi-omics clustering based on matrix factorization
Authors: Qiu Yushan , Guo Dong , Zhao Pu , Zou Quan 
Published: May 2024

Abstract

Motivation
The technology for analyzing single-cell multi-omics data has advanced rapidly and has provided comprehensive and accurate cellular information by exploring cell heterogeneity in genomics, transcriptomics, epigenomics, metabolomics and proteomics data. However, because of the high-dimensional and sparse characteristics of single-cell multi-omics data, as well as the limitations of various analysis algorithms, the clustering performance is generally poor. Matrix factorization is an unsupervised, dimensionality reduction-based method that can cluster individuals and discover related omics variables from different blocks. Here, we present a novel algorithm that performs joint dimensionality reduction learning and cell clustering analysis on single-cell multi-omics data using non-negative matrix factorization that we named scMNMF. We formulate the objective function of joint learning as a constrained optimization problem and derive the corresponding iterative formulas through alternating iterative algorithms. The major advantage of the scMNMF algorithm remains its capability to explore hidden related features among omics data. Additionally, the feature selection for dimensionality reduction and cell clustering mutually influence each other iteratively, leading to a more effective discovery of cell types. We validated the performance of the scMNMF algorithm using two simulated and five real datasets. The results show that scMNMF outperformed seven other state-of-the-art algorithms in various measurements.

Availability and implementation
scMNMF code can be found at https://github.com/yushanqiu/scMNMF.
The potential effect of melatonin on in vitro oocyte maturation and embryo development in animals
Authors: Nadri Parisa , Zahmatkesh Azadeh , Bakhtari Azizollah 
Published: May 2024

Abstract
Melatonin is a hormone mainly secreted by the pineal gland during the circadian cycle, with low levels during the daytime and prominent levels during the night. It is involved in numerous physiological functions including the immune system, circadian rhythm, reproduction, fertilization, and embryo development. In addition, melatonin exerts anti-inflammatory and antioxidant effects inside the body by scavenging reactive oxygen and reactive nitrogen species, increasing antioxidant defenses, and blocking the transcription factors of pro-inflammatory cytokines. Its protective activity has been reported to be effective in various reproductive biotechnological processes, including in vitro maturation (IVM), embryo development, and survival rates. In this comprehensive review, our objective is to summarize and debate the potential mechanism and impact of melatonin on oocyte maturation and embryo development through various developmental routes in different mammalian species.
Colour-coded collateral and venous outflow patterns in estimating infarct progression and predicting functional independence for stroke patients in late time window
Authors: Lin Yu , Xing Zhen , Lv Shaomao , Yang Xiefeng , Kang Jianghe , Kang Nannan , Wang Jinan , Cao Dairong 
Published: May 2024

Abstract

Objectives
To investigate whether cerebral collateral and venous outflow (VO) patterns on colour-coded multi-phase computed tomography angiography (mCTA) can estimate ischaemic core growth rate (IGR) and predict 90-day functional independence for patients with late-presenting acute ischaemic stroke (AIS).

Methods
The retrospective analysis included 127 AIS patients with a late time window. All patients underwent baseline mCTA with colour-coded reconstruction and computed tomography perfusion. Both collateral score and VO score on colour-coded mCTA maps were analysed and recorded. The IGR was calculated as ischaemic core volume divided by the time from onset to imaging. A 90-day modified Rankin Scale score of 0-2 was defined as functional independence. Kendall’s Tau-b analysis was used for nonparametric correlation analysis. Propensity scores, logistic regressions, and receiver operator characteristic (ROC) curves were applied to construct the prediction model.

Results
Moderate correlations were found between collateral delay and IGR (Tau-b = -0.554) and between VO and IGR (Tau-b = -0.501). High collateral score (odds ratio = 3.01) and adequate VO (odds ratio = 4.89) remained independent predictors for 90-day functional independence after adjustment. The joint predictive model, which integrated the VO score and clinical features, demonstrated an area under the ROC curve (AUC) of 0.878. The AUCs of collateral score and VO score were 0.836 and 0.883 for outcome prediction after adjustment.

Conclusions
Cerebral collateral and VO patterns based on colour-coded mCTA can effectively predict infarct progression and 90-day clinical outcomes, even for AIS patients beyond the routine time window.

Advances in knowledge
Colour-coded mCTA is a readily understandable post-processing technique for the rapid assessment of collateral circulation and VO status in stroke imaging. A moderate correlation was observed between the characteristics of collateral delay/VO on colour-coded mCTA and IGR in patients with AIS. Both high-quality collateral circulation and “red superficial middle cerebral vein sign” can predict 90-day functional independence even for patients beyond the routine time window.
How Preoperative Investigations Affect the Management of Bariatric Patients - Results of a Cohort Study of 897 Patients
Authors: Poljo A , Schneider R , Süsstrunk J , Klasen J M , Billeter A T , Peterli R , Kraljević M 
Published: May 2024

Abstract

Background
Poorly defined preoperative diagnostic protocols worldwide vary in their emphasis on comprehensive investigations, with some prioritizing patient safety while others question routine procedures.

Aims
This study explores how diverse preoperative findings, from inflammatory processes to structural abnormalities, significantly influence patients’ management and the choice of bariatric procedures, underscoring the complexity in decision-making for individualized surgical interventions based on a cohort study's findings.

Methods
In a retrospective analysis of prospective data of over 1000 bariatric surgery patients from January 2017 to December 2022, we specifically included those who underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG). In all patients, preoperative upper endoscopy was performed, with selected candidates also undergoing additional procedures like upper GI series and esophageal manometry, especially when LSG was planned. The study primarily analyzed the impact of preoperative examinations on therapeutic approaches.

Results
In this study, 897 patients were included, with 741 undergoing laparoscopic LRYGB and 156 LSG. All patients underwent upper endoscopy, revealing common findings such as type C gastritis, gastroesophageal reflux disease, and detection of Helicobacter pylori. Upper endoscopy prompted a therapeutic change in 216 patients (24.3%), resulting in a number needed to screen (NNS) of 4.1, with no significant differences based on the initially scheduled procedure. Preoperatively, upper GI series were more frequently conducted before planned LSG, uncovering hiatal hernias and motility disorders. However, no change in the surgical procedure resulted from upper GI series findings. Esophageal manometry, primarily performed for LSG, indicated normal findings in 84.6%, with a procedural change in 3 patients (2.0%). Overall, 14 (1.6%) patients experienced a change in the planned procedure, with 12 changes prompted by preoperative findings and two by technical difficulties.

Conclusion
We recommend routine upper endoscopy for all bariatric surgery patients, with additional manometry for planned LSG. Upper GI series should be reserved for selected cases and specific clinical indications.
Proficiency and Depth of Surgical Education in Switzerland is Heading in the Wrong Direction
Authors: Schöb T , Klein I 
Published: May 2024

Abstract

Background
In Switzerland, surgical resident training has become increasingly difficult over the past decades for numerous reasons. While the number of surgical residents has doubled over twenty years, the average workweek dropped from 70 to 50 hours. At the same time, the surgical caseload increased only marginally as opposed to the proportion of administrative responsibilities, resulting in a substantial decrease of intraoperative exposure in surgical residency training.

Aims
To assess the surgical exposure of our residents.

Methods
This study is a review of all performed surgical procedures in the field of general, abdominal, thoracic, vascular and trauma surgery at a category-A Cantonal hospital in Switzerland, performed from September 1st 2021 to August, 31st 2023. The primary outcome was surgical exposure of residents as primary, secondary, and assisting surgeons. Secondary outcomes were case-distribution during daytime workhours as opposed to on-call hours per resident.

Results
The surgical exposure of a surgical resident at our cantonal hospital as primary and secondary surgeon was 41.19 and 39.06 minutes respectively per week. This surgical exposure as was paired with a total of 127.46 minutes as assisting surgeons per week. On average this results in 1.34 operations per week and 60.3 cases per year per surgical resident. 73.51% of these cases are performed during daytime work hours and 26.49% during on-call hours.

Conclusion
To fulfill the minimal number of 510 cases in the mandatory FMH surgical catalogue of becoming a general surgeon, a total residency period of 8.46 years would become necessary to take the exam based on the average number of operative cases in this category-A teaching hospital which is considerably longer compared to residency training 20 years ago. While surgical procedures and techniques continue to become more complex, the need to exploit ways to maintain a sufficient level of surgical exposure inside and outside the OR is eminent.
Autonomous and Self-sustained Circadian Oscillators Displayed in Human Primary Parathyroid Cell Culture Drive Parathormone Secretion
Authors: Petrenko V , Dibner C , Golaz O , Triponez F , de Vito C , Demarchi M S 
Published: May 2024

Abstract

Background
Most cells in our body possess circadian oscillators controlling diurnal rhythmicity of body metabolism. The role of molecular clocks in regulating the function and disfunction of human parathyroid gland (PG), responsible for calcium homeostasis, has not been unraveled. Hyperparathyroidism is a common endocrine pathology, characterized by an unadapted PTH secretion to calcium levels.

Aims
Here we aimed at characterizing molecular makeup of circadian clocks in human primary parathyroid cell culture (HPPCC), and at establishing differential transcriptional patterns of normal and pathological PGs.

Methods
RNA extracted from normal, adenomatous, and hyperplastic PG tissues was subjected to RNA sequencing (RNAseq) analysis. The rim of normal PG tissue was dissected from parathyroid adenoma specimens based on the higher autofluorescence intensity assessed by the near infra-red imaging. HPPCCs were established from adenomatous and hyperplastic PG biopsies. Efficient circadian clock disruption was achieved in HPPCCs by small interfering RNA-mediated knockdown of CLOCK. The functionality of circadian clock machinery was assessed by continuous recording of circadian bioluminescence introduced via lentivectors and paralleled with around-the-clock measurement of PTH secretion using perfusion system.

Results
The RNAseq analyses revealed transcriptional signatures that distinguished between pathological and normal PGs, and among adenomatous and hyperplastic PGs. We report, for the first time, robust anti-phasic circadian rhythmicity of Per2-luciferase and Bmal1-luciferase reporters in HPPCCs synchronized in vitro. Strikingly, we observed circadian rhythmicity of PTH secretion by parathyroid adenoma cells. Moreover, clock disruption in PG adenoma cells has an impact on transcription of functional genes.

Conclusion
Our data indicate presence of cell-autonomous molecular clock in human PG cells paralleled with circadian rhythmic PTH secretion and provide large-scale transcriptional pattern of parathyroid adenoma and hyperplastic tissues.
Syndromic MEN1 Parathyroid Adenomas Consist of Both Subclonal Nodules and Clonally Independent Tumors
Authors: Nesti C , Bräutigam K , Niederle B , Perren A , Kaderli R M 
Published: May 2024

Abstract

Background
Primary hyperparathyroidism with parathyroid tumors is a characteristic presentation in Multiple Endocrine Neoplasia Type 1 (MEN1), historically referred to as "primary hyperplasia." The question of whether these tumors signify a multi-glandular clonal disorder or hyperplasia remains inconclusive. Loss of Menin protein expression serves as a reliable surrogate marker for biallelic inactivation and indicates a mutation in the MEN1 gene. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene, associated with MEN4, encodes the p27 protein, whose expression is inadequately explored in the context of syndromic MEN1.

Aims
The aim was to explore the molecular basis of syndromic MEN1 parathyroid adenomas, identifying hyperplasia, multiple independent clones, and the extent of Menin loss. Additionally, p27 expression was assessed to evaluate its potential in indicating a germline mutation, especially in distinguishing MEN4 as a clinical alternative to MEN1.

Methods
In this investigation, we examined histomorphology and protein expression of Menin and p27 in parathyroid adenomas from 25 patients in two independent, well-characterized MEN1 cohorts. Loss of heterozygosity (LOH) patterns were evaluated using fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Furthermore, next-generation sequencing (NGS) was conducted on eleven nodules from four MEN1 patients.

Results
Morphologically, the majority of MEN1 adenomas displayed multiple distinct nodules, characterized by predominantly lost Menin expression and reduced p27 protein expression. FISH analysis indicated that most nodules exhibited MEN1 loss, with or without centromere 11 loss. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors.

Conclusion
Syndromic MEN1 parathyroid adenomas, therefore, consist of multiple clones with subclones, aligning with the current framework of the novel WHO classification of parathyroid tumors (2022). The observed loss of p27 expression in a significant fraction of MEN1 parathyroids emphasizes the need for caution when inferring MEN4 solely based on p27 expression.
Our Experience with Primary Trapeziometacarpal Implant Arthroplasty in Severely Comminuted Rolando Fractures
Authors: Greminger M , Buechel R 
Published: May 2024

Abstract

Background
The concept of primary joint replacement in severely comminuted fractures in elderly patients has proven to be a suitable treatment option in the shoulder, elbow and knee joint. Comminuted intra-articular fractures of the first metacarpal base can pose significant technical challenges, and no established gold standard treatment currently exists. Conventional methods like open reduction and internal fixation or external fixation are commonly employed, emphasizing the importance of anatomical reduction for restoring the articular surface. However, achieving articular surface congruity is often unattainable in severely comminuted intra-articular fractures, leading to short-term joint stiffness and instability, as well as long-term complications like secondary osteoarthritis.

Aims
This case report aims to share our experience with the use of primary trapeziometacarpal implant arthroplasty in the treatment of two patients with severely comminuted Rolando fractures.

Methods
In two cases of comminuted Rolando fractures, a primary trapeziometacarpal prosthesis (MAÏA™) was implanted based on preoperative decision-making facilitated by 3D-CT analysis. Patient’s visual analogue score for pain, range of motion, pinch and grip strength compared to the contralateral side were asked and examined.

Results
Both patients exhibited successful adaptation to their daily routines within a three-month postoperative period. No complications, such as cup or stem loosening or dislocation, were identified. Both patients almost reached equal range of motion, pinch and grip strength compared to the contralateral side.

Conclusion
The use of primary trapeziometacarpal implant arthroplasty seems to be a viable alternative for managing severely comminuted Rolando fractures, particularly in elderly patients and those with pre-existing osteoarthritis. This approach offers promising outcomes. Studies with other implant arthroplasties have shown better outcomes in patients treated primarily, than after several failed surgeries. We suggest the same is true for the trapeziometacarpal joint. Further studies are necessary to validate the efficacy of this intervention in a larger cohort of patients.
Correlation of Self-Assessed Manual Dexterity and Actual Performance in Surgical Simulation – One Year Follow Up
Authors: Hillinger S , Brunn T , Opitz I , Held U , Hofer L , Zellweger N , Battilana B , Werner R 
Published: May 2024

Abstract

Background
Simulation training has proved to be beneficial in many fields of professions including medicine and might be included already during medical school.

Aims
We evaluated if medical students rate their manual dexterity as good or above average and if this self-assessment (SA) correlates with the actual performance in a surgical simulation.

Methods
Basic surgical tasks have been performed by medical students in the 3rd and 4th year for a total of 4 rounds on 2 identical Lap-Sim® surgical simulators. Three questionnaires, before and after the simulation as well as follow up after 1 year had to be answered.
Descriptive statistics stratified by career goal (surgical/ undecided/ nonsurgical) for outcomes of simulation parameters are reported. Associations between surgical career goal and SA of manual dexterity with three performance parameters (tissue damage, time and path length) are estimated in linear regression models.

Results
Out of 102 participating students 41 stated surgery as their career goal, 18 a nonsurgical field, and 43 were undecided. 87.8% of the surgical group rated their dexterity as good or above average (86.1% in the undecided group), 88.9% of the nonsurgical group as below average or good. A positive association of SA with tissue damage has been found statistically significant (p=0.033).
One year after the simulation (n=97) 13.4% changed their career goal from undecided to surgical, whereas 8.2% changed from undecided to non-surgical. 92.7% wanted to have simulation training integrated into the curriculum.

Conclusion
A correlation of self-assessed manual dexterity has been found in the surgical group for tissue damage, but not for time and path length. Simulation training might help students in decision making for a surgical field and therefore recruit future surgeons, which could be shown in the one-year follow-up.
Impact of Transjugular Intrahepatic Portosystemic Shunt on Hepatocellular Carcinoma: Prospective Cohort of Liver Transplant Candidates’ Analysis
Authors: El Hajji S , Toso C , Möckli B , Compagnon P , Lacotte S , Cauchy F 
Published: May 2024

Abstract

Background
Transjugular intrahepatic portosystemic shunt (TIPS) is used to mitigate the side effects of portal hypertension. However, its impact on hepatocellular carcinoma (HCC) remains unclear.

Aims
We aimed to evaluate its effect on HCC dynamics and patients’ survival.

Methods
We analysed 43’734 liver transplant candidates diagnosed with HCC from the prospective Scientific Registry of Transplant Recipients database (1985-2022). A total 7’404 patients with and without TIPS were propensity score matched 1:3. We assessed wait-list changes in total tumor volume, HCC count, and alpha-fetoprotein levels. We examined survival rates from time of listing and post-transplantation, as well as the incidence of HCC recurrence post-transplantation.

Results
Pre-matching, TIPS patients exhibited poorer liver function and less advanced HCCs. Post-matching, TIPS correlated with a decrease in HCC nodules count (-0.24 vs 0.11, p = 0.008) over a median waiting period of 225 days (IQR 94; 441) and better overall survival rate from listing (93.0% vs 89.1% at one year, p = 0.0003). TIPS was not associated with altered changes in waitlist tumor volume (0.26 vs -0.07 cm3/month, p = 0.26) and AFP (14.62 vs 12.67 ng/mL, p = 0.79) compared to the non-TIPS group. Post-transplant survival rates (91.8% vs 91.7% at one year, p = 0.25) and HCC recurrence (5.2% vs 5.4% at 5 years, p = 0.73) were similar, with a median follow-up of 5.6 years (IQR 2.7; 9.6)

Conclusion
TIPS improved waitlist survival and is associated with decreased HCC nodule count, potentially due to a better efficacy in HCC treatment. However, TIPS did not have a measurable impact on HCC growth or aggressiveness.
Long-Term Ex Situ Normothermic Kidney Perfusion
Authors: Sousa Da Silva R X , Binz J , Huwyler F , Helmchen B M , Mancina L , Wernlé K , Kalbas Y , Müller M , Hefti M , Becker D , Weisskopf M , Tibbitt M W , Dutkowski P , Clavien P A , Kron P 
Published: May 2024

Abstract

Background
Marginal grafts are increasingly considered for transplantation due to the widening gap of available donor grafts and waiting recipients. Graft assessment and repair prior to implantation are therefore essential to minimize the risk of failure. Normothermic perfusion has not been widely evaluated for kidney grafts, with existing perfusions limited to 2 days.

Aims
The aim of this study was to develop a long-term (&gt;3 days) normothermic ex situ swine perfusion model in kidney grafts, while maintaining organ viability. We also wanted to investigate possible regenerative processes of the kidney during this period outside the donor animal.

Methods
Swine kidneys were retrieved with minimal injury. After cannulation, organs were perfused at 37°C for up to several days in a newly designed normothermic ex situ device with automated blood gas and glucose regulation, addition of nutrition, antibiotics, and vasodilators. Kidney biopsies, urine and perfusate samples were taken daily for analysis as well as markers of viability.

Results
In total 17 kidneys were perfused. Four kidneys were perfused for 3 or more days. Viability was maintained up to 4 days without histological evidence of glomerular and minimal to moderate tubular necrosis. We observed upregulation of ki67 and pH3 in tubular cells with mean values of up to 14.2% and 2.2% respectively. This expression of ki67, a proliferation associated protein, correlated with the duration of ex situ perfusion.

Conclusion
This is the first report of normothermic kidney perfusion for up to 4 days with unprecedented observation of upregulated ki67 and pH3 after multiple days of perfusion. These preclinical results open the door for development of long-term perfusion protocols for discarded human grafts while also hinting at limitations and challenges.