bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal relationships between leukocyte telomere length and female reproductive system diseases: A bidirectional Mendelian randomization study
Authors: She Jun-Sen , Liu Rui , Mao Su-Qing , Wu Xiao-Jing , Ding Meng-Zhen , Wang Ling-Xiang , Cao Yi-Ning , Wu Hai-Yan , Long Yu-Hang , Guo Fei , Zhou Bo-Kang , Gao Ling , Huang He-Feng 
Published: September 2024

Objective:
Although numerous observational studies have revealed a correlation between leukocyte telomere length (LTL) and female reproductive system diseases (RSDs), the findings of these studies have tended to be consistent. In this study, we accordingly sought to clarify the causal relationships between LTL and RSDs.

Methods:
We performed a bidirectional two-sample Mendelian randomization (MR) analysis using pooled statistics from genome-wide association studies of LTL and nine female RSDs. The final results were analyzed using five MR methods, with the inverse variance weighted (IVW) method used as the primary outcome. We applied MR-PRESSO to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy.

Results:
In the forward MR analysis, a genetic prediction of longer LTLs was found to be causally associated with higher risks of endometriosis (IVW: OR = 1.25, 95%CI: 1.06–1.46, P = 0.008), leiomyoma of the uterus (IVW: OR = 1.73, 95%: 1.52–1.98, P = 4.9E-16) and ovarian cysts (IVW: OR = 1.31, 95%:1.19–1.45, P = 1.5E-07). In the reverse MR results, female RSDs were shown to have no significant effect on LTLs (all P-values > 0.05). Sensitivity analysis confirmed the robustness of these results.

Conclusions:
Our findings substantiate the assumption that a genetically predicted longer LTL elevates the risk of endometriosis, leiomyoma of the uterus, and ovarian cysts, with no influence of RSDs on LTL. These findings contribute to establishing a causal link between LTL and RSDs, overcoming the constraints of earlier observational studies. They also imply that LTL could potentially serve as a biomarker for the occurrence of endometriosis, leiomyoma of the uterus, and ovarian cysts.
Perioperative Fully Closed-loop versus Usual Care Glucose Management in Adults Undergoing Major Abdominal Surgery – A Two-centre Randomised Controlled Trial
Authors: Krutkyte Gabija , Goerg Arna M C , Grob Christian A , Piazza Camillo D , Rolfes Eva-Dorothea , Gloor Beat , Wenning Anna S , Beldi Guido , Kollmar Otto , Hovorka Roman , Wilinska Malgorzata E , Herzig David , Vogt Andreas P , Girard Thierry , Bally Lia 
Published: September 2024

Objective:
To assess the efficacy and safety of fully closed-loop (FCL) compared with usual care (UC) glucose control in patients experiencing major abdominal surgery-related stress hyperglycaemia.

Summary Background Data:
Major abdominal surgery-related stress and periprocedural interventions predispose to perioperative hyperglycaemia, both in diabetes and non-diabetes patients. Insulin corrects hyperglycaemia effectively, but its safe use remains challenging.

Methods:
In this two-centre randomised controlled trial, we contrasted subcutaneous FCL with UC glucose management in patients undergoing major abdominal surgery anticipated to experience prolonged hyperglycaemia. FCL (CamAPS HX, Dexcom G6, mylife YpsoPump 1.5x) or UC treatment was used from hospital admission to discharge (max 20 d). Glucose control was assessed using continuous glucose monitoring (masked in the UC group). The primary outcome was the proportion of time with sensor glucose values in target range 5.6-10.0 mmol/L.

Results:
Thirty-seven surgical patients (54% pancreas, 22% liver, 19% upper gastrointestinal, 5% lower gastrointestinal), of whom 18 received FCL and 19 UC glucose management, were included in the analysis. Mean±SD percentage time with sensor glucose in target range was 80.1±10.0% in the FCL and 53.7±19.7% in the UC group (P<0.001). Mean±SD glucose was 7.5±0.5 mmol/L in the FCL and 9.1±2.4 mmol/L in the UC group (P=0.015). Time in hypoglycaemia (<3.0 mmol/L) was low in either group. No study-related serious adverse events occurred.

Conclusions:
The FCL approach resulted in significantly better glycaemic control compared to UC management, without increasing the risk of hypoglycaemia. Automated glucose-responsive insulin delivery is a safe and effective strategy to minimise hyperglycaemia in complex surgical populations.
Risk factors for urinary retention requiring catheterization after ischemic middle cerebral artery stroke
Authors: Chiu Tai-Hua , Chen Yu-Chen , Wu Meng-Ni , Juan Yung-Shun , Lin Yi-Hui , Chen Hao-Wei 
Published: September 2024

Purpose:
Urinary retention is common in patients with ischemic stroke. Therefore, we aimed to identify the risk factors for urinary retention requiring indwelling urinary catheters (IUCs) in patients with acute middle cerebral artery (MCA) ischemic stroke.

Materials and methods:
We retrospectively reviewed the medical records of all patients with acute MCA infarction who required admission to the neurological intensive care unit between January 2009 and December 2019 at our tertiary hospital. Patients who did not need IUCs before the stroke but required them after the stroke were included. Multivariate logistic regression analysis was used to identify the risk factors associated with urinary retention requiring IUCs after 7, 14, 21, and 28 days of stroke.

Results:
A total of 104 patients were included in this study. Among them, 75 (72.2%), 65 (62.5%), 52 (50.0%), and 44 (42.3%) patients required IUCs 7, 14, 21, and 28 days after stroke, respectively. Multivariate logistic regression analysis showed that hypertension was associated significantly with the requirement of IUCs 7 days (odds ratio [OR] = 2.987; P = 0.026) and 14 days (OR = 3.047; P = 0.021) after acute stroke. Furthermore, a higher National Institutes of Health Stroke Scale score was associated significantly with the requirement for IUCs 14 days (OR = 1.096; P = 0.030) and 21 days (OR = 1.091; P = 0.027) after stroke.

Conclusion:
Hypertension and higher National Institutes of Health Stroke Scale scores are associated significantly with urinary retention requiring IUCs after acute ischemic MCA stroke and could serve as risk factors for voiding dysfunction in this population.
The association of 5-alpha reductase inhibitors treatment with prostate cancer in benign prostate hyperplasia patients: A population-based case-control study
Authors: Lee Sz-En , Chiu Kun-Yuan , Wang Shian-Shiang , Cheng Chen-Li , Lin Ching-Heng , Li Jian-Ri 
Published: September 2024

Purpose:
Benign prostatic hyperplasia (BPH) is the most common cause of difficult voiding in elderly men. Alpha-blockers and 5-alpha reductase inhibitors (5ARIs) are evidence-based standards of care in treating BPH according to current guidelines. We have conducted a nationwide population-based study to evaluate the association of 5ARIs treatment with prostate cancer in patients with benign prostate hyperplasia.

Materials and methods:
Between 2005 and 2010, patient data from the National Health Insurance Research Database were obtained. Newly diagnosed patients with BPH were divided into 2 groups: prostate cancer group and BPH group. We conducted a retrospective study on their history of medication usage with 5ARIs. Results were compared with a matched noncancerous control group. The outcome measurements were the incidence and the prostate cancer diagnosis-free survival rate after the BPH index date. Statistical analyses included t test, chi-square test, multivariable logistic regression analysis, and Kaplan-Meier curves with log-rank tests.

Results:
A total of 18,620 newly diagnosed patients with BPH were selected. After eliminating patients according to the exclusion criteria, a total of 17,716 patients were enrolled as the study subjects. Among them, 530 patients (2.99%) developed prostate cancer and 17,186 (97.01%) did not. The mean age of the total case-control study was 69.1 years. The odds ratio of prostate cancer in patients with BPH with 5ARIs usage was 1.14 with a P value of 0.539, indicating that the use of 5ARIs was not associated with a higher risk of developing prostate cancer. Multivariate analysis showed no significant intergroup difference in the risk of developing prostate cancer (odds ratio = 1.14, 95% CI: 0.75–1.74, P = 0.539). A subgroup survival analysis, observing the time interval from BPH diagnosis to the development of prostate cancer based on 5ARIs usage, revealed a nonsignificant difference in the prostate cancer diagnosis-free survival rate, with a P value of 0.3592.

Conclusion:
The 5ARI usage in patients with BPH was not associated with increased risk of developing prostate cancer. Furthermore, the prostate cancer diagnosis-free survival rate, when stratified based on 5ARIs usage, showed no statistically significant difference. Under our health insurance regulation and clinical practice, 5ARIs are consider safe in treating BPH.
The nuclear lamin network passively responds to both active or passive cell movement through confinements
Authors: Amiri Sirine , Bos Inge , Reyssat Etienne , Sykes Cécile 
Published: September 2024

AbstractPhysical models of cell motility rely mostly on cytoskeletal dynamical assembly. However, when cells move through the complex 3D environment of living tissues, they have to squeeze their nucleus that is stiffer than the rest of the cell. The lamin network, organised as a shell right underneath the nuclear membrane, contributes to the nuclear integrity and stiffness. Yet, its response during squeezed cell motility has never been fully characterised. As a result, up to now, the interpretations on the lamin response mechanism are mainly speculative. Here, we quantitatively map the lamin A/C distribution in both a microfluidic migration device and a microfluidic aspiration device. In the first case, the cell is actively involved in translocating the nucleus through the constriction, while in the second case, the cell behaves as a passive object that is pushed through the constriction by an external pressure. Using a quantitative description of the lamin shell response based on mass conservation arguments applied on the fluorescence signal of lamin, we show that in both cases of migration and aspiration, the response of the lamin network is passive. In this way, our results not only further elucidate the lamin response mechanism, but also allow to distinguish this passive deformation response from other active responses that may occur when the nucleus is squeezed through constrictions.
Generation of synthetic TSPO PET maps from structural MRI images
Authors: Ferrante Matteo , Inglese Marianna , Brusaferri Ludovica , Toschi Nicola , Loggia Marco L 
Published: September 2024

AbstractBackgroundNeuroinflammation, a pathophysiological process involved in numerous disorders, is typically imaged using [11C]PBR28 (or TSPO) PET. However, this technique is limited by high costs and ionizing radiation, restricting its widespread clinical use. MRI, a more accessible alternative, is commonly used for structural or functional imaging, but when used using traditional approaches has limited sensitivity to specific molecular processes. This study aims to develop a deep learning model to generate TSPO PET images from structural MRI data collected in human subjects.MethodsA total of 204 scans, from participants with knee osteoarthritis (n = 15 scanned once, 15 scanned twice, 14 scanned three times), back pain (n = 40 scanned twice, 3 scanned three times), and healthy controls (n=28, scanned once), underwent simultaneous 3T MRI and [11C]PBR28 TSPO PET scans. A 3D U-Net model was trained on 80% of these PET-MRI pairs and validated using 5-fold cross-validation. The model’s accuracy in reconstructed PET from MRI only was assessed using various intensity and noise metrics.ResultsThe model achieved a low voxel-wise mean squared error (0.0033 ± 0.0010) across all folds and a median contrast-to-noise ratio of 0.0640 ± 0.2500 when comparing true to reconstructed PET images. The synthesized PET images accurately replicated the spatial patterns observed in the original PET data. Additionally, the reconstruction accuracy was maintained even after spatial normalization.ConclusionThis study demonstrates that deep learning can accurately synthesize TSPO PET images from conventional, T1-weighted MRI. This approach could enable low-cost, noninvasive neuroinflammation imaging, expanding the clinical applicability of this imaging method.
ACE1 Does Not Influence Cerebral Aβ Degradation or Amyloid Plaque Accumulation in 5XFAD Mice
Authors: Jeon Sohee , Alia Alia O. , Popovic Jelena , Vassar Robert J. , Cuddy Leah K. 
Published: September 2024

AbstractAlzheimer’s disease (AD) is the most common form of dementia, and multiple lines of evidence support the relevance of Aβ deposition and amyloid plaque accumulation in the neurotoxicity and cognitive decline in AD. Rare mutations in angiotensin-converting-enzyme-1 (ACE1) have been highly associated with late onset AD patients; however, the mechanism for ACE1 mutation in AD pathogenesis is unknown. Given the relevance of ACE1 with AD and the strong association of Aβ to AD pathogenesis, we investigated whether ACE1 degrades Aβ and affects amyloid burden in 5XFAD micein vivo. To investigate this, we analyzed 6-month-old 5XFAD mice with ACE1 loss of function. ACE1 loss of function was mediated either by crossing 5XFAD mice to ACE1 conditional knockout mice or administering 5XFAD mice with the ACE1 inhibitor enalapril. Our analyses revealed that ACE1 loss of function through both genetic and pharmacological methods does not affect amyloid plaque load and neuroinflammation in the hippocampus and cortex of 5XFAD mice.
Histopathological profile of triple negative breast carcinomas seen in patients in National Hospital, Abuja over a 10-year period (January 2010-December 2019)
Authors: Benye Tolulope A. , Jibrin Paul G. , Achusi Ben I. , Olah Friday G. , Nwana Edmund J.C. 
Published: September 2024

ABSTRACTBackgroundTriple negative breast carcinoma (TNBC) cases in Africa and the black race which are most commonly seen among the reproductive age group are highly aggressive and have a high mortality rate. Based on its protein expression using immunohistochemical methods it does not express the hormone receptors (oestrogen and progesterone) and the human epidermal growth factor receptor 2 (HER2). As a result the only means of treating TNBC patients so far is by conventional chemotherapy +/- radiotherapy. Even then only 50.0 % of these patients will respond to the chemotherapy. Further studies which may help improve treatment and survival in these patients are important.ObjectiveThis study is aimed at knowing the histopathological profile of TNBCs in Abuja with the expression of androgen receptor; an important marker in these patients.MethodTwo hundred formalin-fixed paraffin embedded TNBC tissue blocks were selected for the study. The histological type and their respective histological grades (based on the Nottingham grading system) were noted from the haematoxylin and eosin(H&E) sections. Immunohistochemical staining was done using antibodies against androgen receptor (Biocare) and CK5/6 (Invitrogen) with in-house controls. The androgen receptor and CK5/6 expressions were analysed using a semi-quantitative scoring method: - A tumour was considered positive for LAR if ≥ 1.0 % of tumour cell nuclei were staining and positive for CK5/6 if ≥10.0 % of tumour cells had membrane staining. Other biographic data like tumour size, presence or absence of lymphovascular permeation were also analysed. Correlation between the histological types and grades were also done using SPSS version 21 statistical package.ResultsThe 30-49 age group had the highest frequency of TNBC. The commonest histological type seen among TNBCs is Invasive carcinoma; NST at 93.0%. The most frequent histological grade is grade 2 at 56.0 %. The androgen receptor subtype constituted 19.0 %. The basal subtype formed 28.5 % of the total sample size. There was no significant correlation between the histological type and grade of TNBC. 73.3% of the patients had tumour size of pT1 and pT2.ConclusionThis study shows that the percentage of androgen positive cases among triple negative breast carcinomas is significant enough to warrant routine luminal AR testing for TNBCs. Furthermore, this study has shown that the most frequent histological type is Invasive carcinoma; Non-specific type (NST) regardless of the molecular subtype and presence or absence of lympho-vascular permeation. It has also shown that the most frequent histological grade seen among patients with TNBCs is Grade 2.
Social Determinants of Health Factors Associated with Metabolic Dysfunction-Associated Steatotic Liver Disease Prevalence and Severity: A Systematic Review and Meta-analysis
Authors: Abu-Rumaileh Mohammed , Dhoop Sudheer , Pace Jordan , Qapaja Thabet , Martinez Maria Elena , Tincopa Monica , Loomba Rohit 
Published: September 2024

ABSTRACTBackground & AimsSocial determinants of health (SDOH) impact disease risk and severity leading to health disparities and impeding health equity. Though important in mitigating adverse health outcomes, SDOH impacting metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence and severity are understudied and results are conflicting. The aim of this systematic review and meta-analysis was to assess the impact of specific SDOH factors on MASLD disease burden for adults in the United States (US).MethodsWe searched MEDLINE, Embase and Cochrane databases per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies from January 2010-May 2024 were included. Quantitative studies of adults in the US that evaluated SDOH beyond race/ethnicity were included. Outcomes included prevalence of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), MASH-associated advanced fibrosis or cirrhosis and clinical outcomes.ResultsWe identified 18 studies comprising of 547,634 total subjects from 11 unique cohorts. Nine studies evaluated MASLD prevalence, three MASH prevalence, eight MASH-associated advanced fibrosis/cirrhosis prevalence, and nine clinical outcomes. High diet quality was the most consistent SDOH factor associated with both MASLD and MASH-associated advanced fibrosis/cirrhosis prevalence (summarized OR of 0.76 p <0.01, and 0.74 p <0.01, respectively). Lower income was most consistently associated with risk of clinical outcomes (significant in 3/9 studies).ConclusionsDiet quality was the most consistent SDOH associated with disease prevalence and severity in MASLD, with the remainder of SDOH showing inconsistent associations. Prospective assessments using consistent, validated tools to assess the impact of specific SDOH on MASLD disease burden are needed to inform public health interventions to mitigate health disparities in MASLD.
Evasion of neutrophil-mediated bacterial clearance inPseudomonas aeruginosaisolates from new-onset infections in cystic fibrosis children
Authors: Kwong Kelly , Goldman Sophia , Beauchamp Annie , Malet Karim , Levade Ines , Grana Lucia , Guttman David S. , Waters Valerie , Nguyen Dao 
Published: September 2024

AbstractChronicPseudomonas aeruginosa(PA) infections in cystic fibrosis (CF) patients can persist for decades and are associated with poor clinical outcomes. New-onset PA infections are routinely treated with antibiotics, but unfortunately up to 40% of patients fail eradication therapy due to reasons that are poorly understood. Recently, we found that Persistent PA isolates from CF patients who failed tobramycin eradication therapy were more resistant toin vitroneutrophil-mediated opsonophagocytosis and intracellular bacterial killing (OPK) and were significantly associated with a non-twitching phenotype compared to Eradicated isolates. In this study, we sought to investigate how Persistent isolates evade in neutrophil-mediated bacterial clearancein vitroand whether these PA isolates also persistin vivo. Furthermore, we investigated whether restoring pilus-mediated twitching motility is sufficient to restore susceptibility toin vitroOPK andin vivobacterial clearance. Using primary murine serum and bone marrow-derived neutrophils, we demonstrated that Persistent isolates are resistant to several neutrophil antibacterial functions compared to Eradicated isolates. Additionally, mice failed to clear pulmonary infections caused by Persistent isolates but not Eradicated isolates despite comparable responses in leukocyte recruitment and cytokine responses. We demonstrate that loss of Type IV pilus-mediated twitching motility confers a fitness advantage for a Persistent isolate during a murine pulmonary infection, and restoration of pilus-mediated twitching motility improvesin vivobacterial clearance. Our findings show that resistance to neutrophil-mediated bacterial clearance in Persistent isolates are partly mediated by loss of Type IV pilus-dependent motility and contributes to the persistence of new onset PA infections.
An evolutionarily conserved Hox-Gbx segmentation code in the rice coralMontipora capitata
Authors: He Shuonan , Rangel-Huerta Emma , Hill Eric , Ellington Lacey , Chen Shiyuan (Cynthia) , Robb Sofia , Majerová Eva , Drury Crawford , Gibson Matthew C. 
Published: September 2024

AbstractSegmentation of the gastric cavity is a synapomorphic trait of cnidarians of the class Anthozoa (corals and sea anemones), with different clades forming distinct numbers of segments. In the starlet sea anemoneNematostella vectensis, for example, eight bilaterally positioned gastric segments are generated by the action of a group of Hox-Gbx genes in the developing larval endo-mesoderm. Still, given the range of segment numbers observed in different anthozoans, it remains unclear whether this Hox-Gbx module is evolutionarily conserved and how it might be deployed to generate different numbers of segments. Here, we systematically interrogate the role of Hox-Gbx genes during development of the rice coralMontipora capitata. We first characterize the temporal sequence of segmentation inM. capitatajuveniles and then combine transcriptomic profiling andin situhybridization to identify three conserved homeobox-containing genes,McAnthox8,McAnthox6a.1andMcGbx, which are collectively expressed in the developing endo-mesoderm prior to and during segment formation. The expression boundaries of these genes prefigure the positions of the first six segment boundaries, similar to theirNematostellahomologs. Further, we show that chemical inhibition of BMP activity at the planula stage abolishes the expression of Hox-Gbx genes, leading to the formation of an unsegmented gastric cavity. These findings demonstrate the existence of a functionally conserved Hox-Gbx module in evolutionarily divergent anthozoan species, suggesting that the last common ancestor of all anthozoans likely utilized a similar genetic toolkit to axially pattern the endo-mesoderm into metameric subunits.