bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of the Boruta algorithm to assess the multidimensional determinants of malnutrition among children under five years living in southern Punjab, Pakistan
Authors: Saleem Javeria , Zakar Rubeena , Butt Muhammad Salman , Aadil Rana Muhammad , Ali Zulfiqar , Bukhari Gul Mehar Javaid , Ishaq Muhammad , Fischer Florian
Published: January 2024

Background

Malnutrition causes nutrient deficiencies that have both physical and clinical consequences in severe acute malnutrition children. Globally, there were 47 million wasted children under the age of five in 2019. One in four were located in sub-Saharan Africa, with half being in South Asia. This study aims to apply the Boruta algorithm to identify the determinants of undernutrition among children under five living in Dera Ghazi Khan, one of the marginalized districts of densely populated Punjab Province in Pakistan.

Methods

A multicenter cross-sectional study design was used to collect data from 185 children with severe acute malnutrition aged under five years visiting the OTPs centers located in Dera Ghazi Khan, Punjab, Pakistan. A purposive sampling technique was used to collect data using a pretested structured questionnaire from parents/caregivers regarding family sociodemographic characteristics, child nutrition, and biological and healthcare characteristics. Anthropometric measurements, including height, weight, and mid-upper arm circumference, were collected. The Boruta models were used to incorporate the children’s anthropometric, nutritional, and household factors to determine the important predictive variables for undernutrition using the Boruta package in R studio.

Results

This study included 185 children, with a mean age of 15.36 ± 10.23 months and an MUAC of 10.19 ± 0.96 cm. The Boruta analysis identifies age, mid-upper arm circumference, weaning practices, and immunization status as important predictors of undernutrition. Income per month, exclusive breastfeeding, and immunization status were found to be key factors of undernutrition in children under the age of five.

Conclusion

This study highlights age, mid-upper arm circumference, weaning practices, and immunization status as key determinants of weight-for-height and weight-for-age in children under five years. It also suggests that economic context may influence undernutrition. The findings can guide targeted strategies for combating undernutrition.
Predictive factors for foot pain in the adult population
Authors: Canca-Sanchez Francisco Javier , Morales-Asencio Jose Miguel , Ortega-Avila Ana Belen , Gijon-Nogueron Gabriel , Cervera-Garvi Pablo , Marchena-Rodriguez Ana , Canca-Sanchez Jose Carlos
Published: January 2024

Background

Foot pain has been associated to factors like: fat, body mass index, age increased, female gender and the presence of pathologies. Although evidence is limited. The purpose is to determine the predictive factors for foot pain in the adult population.

Methods

From January to December 2021, 457 patients were > 18 years, gave signed informed consent to take part to this cross sectional study. All completed demographic data and various questionnaires related to pain: Foot Function Index, EuroQoL-5D and Visual Analogue Scale (foot pain). Anthropometric measurements were obtained using McPoil platform and foot posture was assessed by the Foot Posture Index (FPI). To determine whether a volume change is a predictive factor for foot pain, a parameter was established: the volumetric index for footwear (VIF). Factors linked to the presence of pain, including the considered VIF variables, were analyzed through multivariable logistic regression.

Results

Among the study population, 40.7% were male and 59.3% female. The mean age of 39.06 years and a body mass index of 25.58 Kg/cm2. The logistic regression model had a classification capability of 72.4%, a sensitivity of 72.3% and a specificity of 73%, in which, the predictors considered were the variables found to have a significant association with FFI-pain > 45 points,, showed that younger women, with a higher BMI, higher values of right FPI (pronation), poorer overall perceived health and with problems in walking were more likely to experience foot pain.

Conclusion

Predictive factors for foot pain in the adult population include gender, age, Body Mass Index, FPI on the right foot, perceived health and mobility. Clinical implication, the presented measure aids physicians in assessing their patients´ foot pain likelihood.
Application of Kirschner wire placement guided technology in paediatric supracondylar humerus fractures
Authors: Liu Huan , Li Lingzhi , Ding Qirui , GE Yunru , Ding Ying , Wang Shouguo , Fei Haodong
Published: January 2024

Background

To analyze the clinical efficacy of K-wire placement guided technology in paediatric supracondylar humerus fractures.

Methods

A retrospective study was conducted in 105 patients who underwent closed reduction and percutaneous pinning surgeries in our hospital from June 2019 to August 2022. 54 patients treated with a assisted reduction fixation device to assist in closed reduction and percutaneous K-wire cross-fixation were allocated into the Non-guided group, and 51 patients with K-wire placement guided technology to guide K-wire placement were assigned into the Guided group. The operation duration, number of disposable K-wire placement, intraoperative fluoroscopy frequency, Baumann angle, carrying angle, fracture healing time and Flynn score of elbow joint function at the final follow-up were compared between two groups. The postoperative complications of two groups were recorded.

Results

There were significant differences between two groups in terms of operation duration, intraoperative fluoroscopy frequency, and disposable K-wire placement rate (p < 0. 05), while no significant differences of Baumann angle, carrying angle and the fracture healing time between two groups were observed (p > 0. 05). In the control group, ulnar nerve injury in 2 case, pin site infection in 4 cases, mild cubitus varus in 2 cases and loss of reduction in 4 cases were detected. In the study group, ulnar nerve injury in 1 case, pin site infection in 2 cases and loss of reduction in 1 case was observed. There was no significant difference in Flynn scores between two groups.

Conclusion

K-wire placement guided technology is simple and convenient. The application of K-wire placement guided technology could relatively improved disposable K-wire placement rate, shorten the intraoperative fluoroscopy frequencies and reduce complication rates.
Elevated serum CA199 levels in patients suffering type 2 diabetes vs. various types of cancer
Authors: Zhuang Yong , Cai Qingyan , Hu Xin , Huang Huibin
Published: January 2024

Aims

Carbohydrate antigen 199 (CA199) is a standard tumor marker, and recent studies have found elevated in CA199 levels in patients with diabetes. However, there is no systematic measurement and comparison of serum CA199 levels in patients with diabetes and cancer. Here, a detailed description of the changes in serum CA199 levels in patients with type 2 diabetes and various cancers was explored.

Methods

A total of 5,641 participants were screened for clinical laboratory test results of serum CA199 levels over the past three years (2020–2023). This study included 2,464 healthy controls, 688 patients with type 2 diabetes, and 2,489 patients with 16 different types of cancer. Each type of cancer had more than 30 independent serum CA199 level test results. The serum CA199 levels were compared between cancer groups, type 2 diabetes patients, and healthy controls. Additionally, the CA199 levels of cancer patients were compared with those of patients with type 2 diabetes.

Results

The serum CA199 levels of esophagus cancer, lung cancer, pancreatic cancer, ovarian cancer, breast cancer, rectum cancer, prostate cancer, bladder cancer, liver cancer, gastric cancer, cervical cancer, colon cancer, lymphoma, thyroid cancer, intracranial tumors, and nasopharyngeal laryngeal cancer were found to be elevated compared to healthy controls (P < 0.01). In addition, the serum CA199 levels of patients with type 2 diabetes were also significantly elevated compared to healthy controls (P < 0.01). Moreover, the degree of elevation in serum CA199 levels in patients with type 2 diabetes was not significantly different from that observed in some types of cancer, such as esophagus cancer (P = 0.163), breast cancer (P = 0.927), prostate cancer (P = 1.000), bladder cancer (P = 0.406), Lymphoma (P = 0.975), thyroid cancer (P = 1.000), intracranial tumors (P = 0.161), nasopharyngeal and laryngeal cancer (P = 1.000).

Conclusions

Serum CA199 levels also increase in type 2 diabetes, and the magnitude of the increase is similar to that seen in some cancers.
Dietary and smoking habits during the exam period and their effect on the academic achievement among Syrian medical students
Authors: Bitar Anas , Barakat Fady , Hawat Angie , Alsaid Bayan
Published: January 2024

Background

Dietary habits are crucial for maintaining overall health and have been shown to impact academic performance. However, little research has been conducted on the specific eating, drinking, and smoking habits during the exam period and their effect on academic performance. Therefore, this study aimed to investigate dietary and smoking habits and their relationship with academic performance among medical students at Damascus University. Findings from this study can inform interventions to improve both dietary habits and academic performance.

Methods

A cross-sectional design was used to investigate the association between dietary habits during the exam period and academic performance among 608 medical students. Data were collected using a self-administered paper-based questionnaire that was randomly distributed across multiple classes. The statistical analysis employed Spearman’s rank correlation and multiple linear regression to examine the relationship between the different amounts of diet behaviour during the exams and the reported average students’ grades from the last two semesters. The regression model was adjusted for age, sex, residency type, and residency partners.

Results

In both Spearman's rank correlation and multiple linear regression analyses, we observed consistent negative associations between specific dietary habits and self-reported average grades. These included daily consumption of tea (B = -0.334, p = 0.022), instant coffee (B = -0.682, p = 0.001), and weekly fast food consumption (B = -0.583, p = 0.038). Notably, traditional coffee was found to be significant in the Spearman analysis but did not exhibit significance in the regression analysis. Furthermore, the regression analysis revealed a negative association between water pipe consumption and academic performance (B = -0.700, p = 0.049). No significant association was observed between other dietary habits, cigarette smoking, and academic performance.

Conclusions

The study highlights a negative, but weak, association between academic achievement and specific dietary habits during the exam period. However, further longitudinal studies are needed to establish causal relationships. Additionally, the study suggests exploring the impact of other habits such as study and sleeping habits, which may have a more significant impact on academic achievement.
Factors influencing the selection criteria of Saudi board orthopedic surgery applicants: a national survey of program directors
Authors: AlAssiri Suhail S. , Alshahir Alwaleed A. , Al Eissa Sami I. , Al Helal Fahad H. , Konbaz Faisal M , Abaalkhail Majed S. , Al Jehani Rayed M. , Mohabbat Abdullah F. , AlSheikh Khalid A.
Published: January 2024

Background

Annually, medical students vie to secure a seat with an orthopedic residency program. This rigorous competition places orthopedic surgery as one of the most competitive specialties in the medical field. Although several international studies have been published regarding the factors that influence program directors when choosing their ideal applicant, the data for Saudi Arabia in that regard is absent.

Methods

In this cross-sectional study, we aimed to survey all orthopedic program directors regarding the factors that influence them when choosing their ideal orthopedic surgery applicant. A survey was sent to all program directors via email during the month of August 2022. A reminder was sent 2 weeks later to maximize the response rate. The survey was completed by 22 out of 36 orthopedic program directors, which gave us a response rate of 61.11%.

Results

In this study, 22 orthopedic surgery program directors responded to our survey. When program directors were asked to rank the factors of residency selection criteria, the top ranked factors were good impression on interviews; prior experience in orthopedic surgery with, for example, electives; and performance on ethical questions during interviews, with means of 9.18, 8.95, and 8.82 out of 10, respectively. Furthermore, program directors preferred letters of recommendation from recommenders that they personally know, clinical experience such as electives taken at the program director’s institution, and the quality of publications as the most important aspects of research. Most program directors (90.9%) relied on their residents’ and fellows’ opinions when selecting candidates, and 77.3% did not think gender has an influence on selection of applicants.

Conclusion

By providing comprehensive data regarding the factors that influence and attract program directors of orthopedic surgery when choosing residency candidates. With the data provided by this study, applicants for orthopedic surgery have the advantage of early planning to build a strong application that may help persuade program directors to choose them.
Comprehensive review and expanding the genetic landscape of Cornelia-de-Lange spectrum: insights from novel mutations and skin biopsy in exome-negative cases
Authors: Tehrani Fateh Sahand , Mohammad Zadeh Nadia , Salehpour Shadab , Hashemi-Gorji Farzad , Omidi Ashkan , Sadeghi Hossein , Mirfakhraie Reza , Moghimi Parinaz , Keyvanfar Sepideh , Mohammadi Sarvaleh Sepideh , Miryounesi Mohammad , Ghasemi Mohammad-Reza
Published: January 2024

Background

Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder characterized by a range of physical, cognitive, and behavioral abnormalities. This study aimed to perform a comprehensive review of the literature on CdLS and investigate two cases of CdLS with distinct phenotypes that underwent WES to aid in their diagnosis.

Methods

We conducted a comprehensive review of the literature on CdLS along with performing whole-exome sequencing on two CdLS patients with distinct phenotypes, followed by Sanger sequencing validation and in-silico analysis.

Results

The first case exhibited a classic CdLS phenotype, but the initial WES analysis of blood-derived DNA failed to identify any mutations in CdLS-related genes. However, a subsequent WES analysis of skin-derived DNA revealed a novel heterozygous mutation in the NIPBL gene (NM_133433.4:c.6534_6535del, p.Met2178Ilefs*8). The second case was presented with a non-classic CdLS phenotype, and WES analysis of blood-derived DNA identified a heterozygous missense variant in the SMC1A gene (NM_006306.4:c.2320G>A, p.Asp774Asn).

Conclusions

The study shows the importance of considering mosaicism in classic CdLS cases and the value of WES for identifying genetic defects. These findings contribute to our understanding of CdLS genetics and underscore the need for comprehensive genetic testing to enhance the diagnosis and management of CdLS patients.
Impact of Helicobacter pylori colonization density and depth on gastritis severity
Authors: Peng Jianxiang , Xie Jinliang , Liu Dingwei , Yang Kaijie , Wu Shuang , Liu Dongsheng , Huang Deqiang , Xie Yong
Published: January 2024

Background and objectives

Helicobacter pylori (H. pylori) infection is the most common etiology of chronic gastric. H. pylori gastritis would gradually evolve into gastric atrophy, intestinal metaplasia, dysplasia and malignant lesions. Herein, this study aimed to investigate the potential impact of H. pylori colonization density and depth on the severity of histological parameters of gastritis.

Methods

A prospective monocentric study was conducted from December 2019 to July 2022, enrolling patients with confirmed chronic H. pylori infection via histopathological evaluation. H. pylori colonization status was detected by immunohistochemical staining, pathological changes of gastric specimens were detected by hematoxylin eosin staining. Epidemiological, endoscopic and histopathological data were collected.

Results

A total of 1120 patients with a mean age of 45.8 years were included. Regardless of the previous history of H. pylori eradication treatment, significant correlations were observed between the density and depth of H. pylori colonization and the intensity of gastritis activity (all P < 0.05). Patients with the lowest level of H. pylori colonization density and depth exhibited the highest level of mild activity. In whole participants and anti-H. pylori treatment-naive participants, H. pylori colonization density and depth were markedly correlated with the severity of chronic gastritis and gastric atrophy (all P < 0.05). H. pylori colonization density (P = 0.001) and depth (P = 0.047) were significantly associated with ulcer formation in patients naive to any anti-H. pylori treatment. No significant associations were observed between the density and depth of H. pylori colonization and other histopathological findings including lymphadenia, lymphoid follicle formation and dysplasia.

Conclusions

As the density and depth of H. pylori colonization increased, so did the activity and severity of gastritis, along with an elevated risk of ulcer formation.
Unlocking the mysteries of VLDL: exploring its production, intracellular trafficking, and metabolism as therapeutic targets
Authors: Chen Jingfei , Fang Zhenfei , Luo Qin , Wang Xiao , Warda Mohamad , Das Avash , Oldoni Federico , Luo Fei
Published: January 2024

Reducing circulating lipid levels is the centerpiece of strategies for preventing and treating atherosclerotic cardiovascular disease (ASCVD). Despite many available lipid-lowering medications, a substantial residual cardiovascular risk remains. Current clinical guidelines focus on plasma levels of low-density lipoprotein (LDL). Recent attention has been given to very low-density lipoprotein (VLDL), the precursor to LDL, and its role in the development of coronary atherosclerosis. Preclinical investigations have revealed that interventions targeting VLDL production or promoting VLDL metabolism, independent of the LDL receptor, can potentially decrease cholesterol levels and provide therapeutic benefits. Currently, methods, such as mipomersen, lomitapide, and ANGPTL3 inhibitors, are used to reduce plasma cholesterol and triglyceride levels by regulating the lipidation, secretion, and metabolism of VLDL. Targeting VLDL represents an avenue for new lipid-lowering strategies. Interventions aimed at reducing VLDL production or enhancing VLDL metabolism, independent of the LDL receptor, hold promise for lowering cholesterol levels and providing therapeutic benefits beyond LDL in the management of ASCVD.
Improved cognition after rifaximin treatment is associated with changes in intra- and inter-brain network functional connectivity
Authors: Casanova-Ferrer Franc , Gallego Juan-José , Fiorillo Alessandra , Urios Amparo , Ríos María-Pilar , León José Luis , Ballester María-Pilar , Escudero-García Desamparados , Kosenko Elena , Belloch Vicente , Montoliu Carmina
Published: January 2024

Background

Rifaximin is a non-reabsorbable antibiotic which acts at gut level, and improves cognition and inflammatory parameters in minimal hepatic encephalopathy (MHE) patients, but not all patients show the same level of response. This study aims to assess brain activity, both within and between brain networks, following rifaximin treatment, considering the differences between response groups as well.

Methods

Twenty-two healthy controls and 53 patients with cirrhosis (22 without and 31 with MHE, diagnosed by Psychometric Hepatic Encephalopathy Score, PHES) performed psychometric, attention and coordination tests, and blood inflammatory parameters were measured. Resting-state functional magnetic resonance imaging (fMRI) acquisitions were performed on controls and MHE patients. Eighteen MHE patients underwent a rifaximin treatment for 6 months, after which all measures were repeated. fMRI images were analysed and changes after treatment were assessed.

Results

After rifaximin treatment, 13 patients improved their PHES score (Responder patients) while 5 did not (Non-responder patients). No significant decrease in blood ammonia was observed after rifaximin treatment, but there was a decrease in plasma inflammatory cytokines in responder patients. A global effect of rifaximin was detected on the sensorimotor and fronto-parietal networks. Responder patients showed a relative increase of thalamic network connectivity in comparison to non-responder patients. Before treatment, responder and non-responder patients showed connectivity differences in basal ganglia network. The connection of the sensorimotor and thalamic networks between them and with other networks suffered changes after treatment. These connections between networks mostly decreased after treatment. All changes and differences showed a significant level of correlation with the performance of psychometric tests and the blood levels of inflammatory biomarkers.

Conclusions

There was an improvement of the communication between executive, motor and attention-related brain areas, and their functional independence following rifaximin treatment. Patients who respond also show a less deteriorated connection involved in these functions before treatment. Results suggest that the improved inflammatory state of MHE patients, following rifaximin treatment would favour the observed changes in brain function and enhanced cognitive performance.
The relationship between structural changes in paraspinal muscles and intervertebral disc and facet joint degeneration in the lumbar spine of rats
Authors: Skidanov Artem , Ashukina Nataliya , Maltseva Valentyna , Skidanov Mykyta , Danyshchuk Zinaida , Radchenko Volodymyr
Published: January 2024

Background

Degenerative spine disease is one of the largest causes of disability worldwide and has a multifactorial aetiology. Determining the leading causes of this multifactorial disease could help create new treatment approaches.

Purpose

Study the impact of degenerative changes in the paraspinal muscles caused by local (prolonged compression) or systemic (high-fat diet) factors on the structure of the intervertebral discs (IVDs) and facet joints of the lumbar spine in rats.

Methods

The study was conducted using two animal models to create degenerative changes in the paraspinal muscles of 10 white laboratory rats for 90 days and five control rats: 1) high-fat diet model (model 1) involved keeping the rats on a high calorie diet; 2) compression model (model 2) involved binding the paraspinal muscles from L2 to S1 using non-absorbable sutures. Histological analysis for the facet joints and IVDs of rats (at the L1–L4 level) with semi-quantitative analysis of the structure conducted used by degeneration grading system for IVDs and cartilage degeneration score (OARSI) for facet joint.

Results

In both models, 90 days after the experiment, the degenerative changes observed in the rats’ IVDs were more severe in the annulus fibrosus than in the nucleus pulposus. The height of the IVD in model 1 did not differ from the control group, but in the model 2 was 1.3 times greater (p < 0.001) compared with control. Degenerative changes in the IVD were scored out 5.3 ± 1.7 in model 1 and 5.32 ± 2.1 in model 2 of a possible 16. The height of the articular cartilage of the facet joints was smaller by 1.5 times (p < 0.001) and 1.4 times (p < 0.001) in model 1 and model 2, respectively, compared to the control. Degenerative changes of facet joint were scored out 3.7 ± 0.6 in model 1 and 3.8 ± 0.6 in model 2 of five points according to the cartilage degeneration score.

Conclusions

It was determined that rats who had structural changes in the lumbar paraspinal muscles as a result of being kept on a high-fat diet or subjected to prolonged compression for 90 days, showed degenerative changes in intervertebral discs and osteoarthritis in facet joints of lumbar spine.
Applying the win ratio method in clinical trials of orphan drugs: an analysis of data from the COMET trial of avalglucosidase alfa in patients with late-onset Pompe disease
Authors: Boentert Matthias , Berger Kenneth I. , Díaz-Manera Jordi , Dimachkie Mazen M. , Hamed Alaa , Riou França Lionel , Thibault Nathan , Shukla Pragya , Ishak Jack , Caro J. Jaime
Published: January 2024

Background

Clinical trials for rare diseases often include multiple endpoints that capture the effects of treatment on different disease domains. In many rare diseases, the primary endpoint is not standardized across trials. The win ratio approach was designed to analyze multiple endpoints of interest in clinical trials and has mostly been applied in cardiovascular trials. Here, we applied the win ratio approach to data from COMET, a phase 3 trial in late-onset Pompe disease, to illustrate how this approach can be used to analyze multiple endpoints in the orphan drug context.

Methods

All possible participant pairings from both arms of COMET were compared sequentially on changes at week 49 in upright forced vital capacity (FVC) % predicted and six-minute walk test (6MWT). Each participant’s response for the two endpoints was first classified as a meaningful improvement, no meaningful change, or a meaningful decline using thresholds based on published minimal clinically important differences (FVC ± 4% predicted, 6MWT ± 39 m). Each comparison assessed whether the outcome with avalglucosidase alfa (AVA) was better than (win), worse than (loss), or equivalent to (tie) the outcome with alglucosidase alfa (ALG). If tied on FVC, 6MWT was compared. In this approach, the treatment effect is the ratio of wins to losses (“win ratio”), with ties excluded.

Results

In the 2499 possible pairings (51 receiving AVA × 49 receiving ALG), the win ratio was 2.37 (95% confidence interval [CI], 1.30–4.29, p = 0.005) when FVC was compared before 6MWT. When the order was reversed, the win ratio was 2.02 (95% CI, 1.13–3.62, p = 0.018).

Conclusion

The win ratio approach can be used in clinical trials of rare diseases to provide meaningful insight on treatment benefits from multiple endpoints and across disease domains.
The glucocorticoid receptor gene (NR3C1) is linked to and associated with polycystic ovarian syndrome in Italian families
Authors: Syed Shumail , Gragnoli Claudia
Published: January 2024

Objectives

Components of the hypothalamic-pituitary axis (HPA) pathway are potential mediators of the genetic risk of polycystic ovarian syndrome (PCOS). Impaired glucocorticoid receptor (NR3C1) expression and function may underlie impaired HPA-axis cortisol activity, thereby also contributing to the increased adrenal cortisol and androgen production present in women with PCOS. In this study, we aimed to identify whether NR3C1 is linked or in linkage disequilibrium (LD), that is, linkage joint to association, with PCOS in Italian peninsular families.

Method

In 212 Italian families with type 2 diabetes (T2D) from the Italian peninsula, previously recruited for a T2D study and phenotyped for PCOS, we used microarray to genotype 25 variants in the NR3C1 gene. We analyzed the 25 NR3C1 variants by Pseudomarker parametric linkage and LD analysis.

Results

We found the novel implication in PCOS risk of two intronic variants located within the NR3C1 gene (rs10482672 and rs11749561), thereby extending the phenotypic implication related to impaired glucocorticoid receptor.

Conclusions

To the best of our knowledge, this is the first study to report NR3C1 as a risk gene in PCOS.
Deciphering the significance of anoikis in bladder cancer and systematic analysis of S100A7 as a potential therapeutic target
Authors: Wang Haoran , Liu Jianyong , Tang Runhua , Hu Jie , Liu Ming , Wang Jianye , Zhang Jingwen , Hou Huimin
Published: January 2024

Background

Bladder cancer is an epidemic and life-threating urologic carcinoma. Anoikis is a unusual type of programmed cell death which plays a vital role in tumor survival, invasion and metastasis. Nevertheless, the relationship between anoikis and bladder cancer has not been understood thoroughly.

Methods

We downloaded the transcriptome and clinical information of BLCA patients from TCGA and GEO databases. Then, we analyzed different expression of anoikis-related genes and established a prognostic model based on TCGA database by univariate Cox regression, lasso regression, and multivariate Cox regression. Then the Kaplan–Meier survival analysis and receiver operating characteristic (ROC) curves were performed. GEO database was used for external validation. BLCA patients in TCGA database were divided into two subgroups by non-negative matrix factorization (NMF) classification. Survival analysis, different gene expression, immune cell infiltration and drug sensitivity were calculated. Finally, we verified the function of S100A7 in two BLCA cell lines.

Results

We developed a prognostic risk model based on three anoikis-related genes including TPM1, RAC3 and S100A7. The overall survival of BLCA patients in low-risk groups was significantly better than high-risk groups in training sets, test sets and external validation sets. Subsequently, the checkpoint and immune cell infiltration had significant difference between two groups. Then we identified two subtypes (CA and CB) through NMF analysis and found CA had better OS and PFS than CB. Besides, the accuracy of risk model was verified by ROC analysis. Finally, we identified that knocking down S100A7 gene expression restrained the proliferation and invasion of bladder cancer cells.

Conclusion

We established and validated a bladder cancer prognostic model consisting of three genes, which can effectively evaluate the prognosis of bladder cancer patients. Additionally, through cellular experiments, we demonstrated the significant role of S100A7 in the metastasis and invasion of bladder cancer, suggesting its potential as a novel target for future treatments.
Fire regimes of the Southern Appalachians may radically shift under climate change
Authors: Robbins Zachary J. , Loudermilk E. Louise , Mozelewski Tina G. , Jones Kate , Scheller Robert M.
Published: January 2024

Background

Increased drought due to climate change will alter fire regimes in mesic forested landscapes where fuel moisture typically limits fire spread and where fuel loads are consistently high. These landscapes are often extensively modified by human land use change and management. We forecast the influence of varying climate scenarios on potential shifts in the wildfire regime across the mesic forests of the Southern Appalachians. This area has a long history of fire exclusion, land use change, and an expanding wildland urban interface. We considered interactions among climate, vegetation, and anthropogenic influences to forecast future fire regimes and changes to the forest structure. We used climate scenarios representing divergent drought patterns (overall drought trend and interannual variability) within a process-based fire model that captures the influence of climate, fuels, and fire ignition on wildfire patterns and suppression.

Results

Compared to simulations using historical climate (1972–2018), future total burned area (2020–2100: 782,302.7 (716,655.0–847,950.3) ha) increased by 42.3% under high drought variability (1,134,888.4 (1,067,437.2–1,202,339.6) ha), 104.8% under a substantial increase in drought trend (1,602,085.7 (1,511,837.5–1,692,334.0) ha), and 484.7% when combined (4,573,925.0 (4,434,910.5–4,712,939.5) ha). Landscape patterns of fire exclusion and suppression drove the spatial variability of fire return intervals (FRI). Our projections indicate wide spatial variability in future fire regimes with some areas experiencing multiple fires per decade while others experience no fire. More frequent fires corresponded with increased oak prevalence and a reduction in the biomass of mesic hardwoods and maple; however, mesic hardwoods remained prevalent under all fire intervals because of their contemporary dominance.

Conclusions

Our study illustrates how future drought–fire–management interactions and a history of fire exclusion could alter future fire regimes and tree species composition. We find that increasing trends in drought magnitude and variability may increase wildfire activity, particularly in areas with minimal fire suppression. In ecosystems where fuel moisture (and not load) is the standard limitation to fire spread, increased pulses of drought may provide the conditions for more fire activity, regardless of effects on fuel loading. We conclude the effects of climate and human management will determine the novel conditions for both fire regime and ecosystem structure.
Unmasking patient diversity: Exploring cognitive and antidepressive effects of electroconvulsive therapy
Authors: Sellevåg Kjersti , Bartz-Johannessen Christoffer A. , Oedegaard Ketil J. , Nordenskjöld Axel , Mohn Christine , Bjørke Jeanette S. , Kessler Ute
Published: January 2024

Background

Electroconvulsive therapy (ECT) is an established treatment for depression, but more data on effectiveness and safety in clinical practice is needed. The aim of this register-based study was to investigate short-term effectiveness and cognitive safety after ECT, evaluated by clinicians and patients. Secondary, we investigated predictors for remission and cognitive decline.

Methods

The study included 392 patients from the Regional Register for Neurostimulation Treatment in Western Norway. Depressive symptoms and cognitive function were assessed with Montgomery-Åsberg Depression Rating Scale and Mini-Mental State Examination (clinician-rated) and Beck Depression Inventory and Everyday Memory Questionnaire (patient-rated). Assessments were done prior to ECT-series and a mean of 1.7 days after (range 6 days before and 12 days after) end of ECT-series. Paired samples t-tests were extended by detailed, clinically relevant subgroups. Predictors were examined using logistic regression.

Results

Clinician- and patient-rated remission rates were 49.5 and 41.0%, respectively. There was a large reduction in depressive symptoms and a small improvement in cognition after ECT, but we also identified subgroups with non-response of ECT in combination with cognitive decline (4.6% clinician-rated, 15.7% patient-rated). Positive predictors for patient- and clinician-rated remission were increasing age, shorter duration of depressive episode, and psychotic features. Antipsychotic medication at the commencement of treatment and previous ECT-treatment gave higher odds of clinician-rated remission, whereas higher pretreatment subjective depression level was associated with lower odds for patient-rated remission. Clinician-rated cognitive decline was predicted by higher pretreatment MMSE scores, whereas psychotic features, increasing age, and greater pretreatment subjective memory concerns were associated with lower odds for patient-rated cognitive decline.

Conclusions

Our study supports ECT as an effective and safe treatment, although subgroups have a less favorable outcome. ECT should be considered at an early stage for older patients suffering from depression with psychotic features. Providing comprehensive and balanced information from clinicians and patients perspectives on effects and side effects, may assist in a joint consent process.
Phase Angle of Bioelectrical Impedance Analysis as an Indicator for Diabetic Polyneuropathy in Type 2 Diabetes Mellitus
Authors: Schimpfle Lukas , Tsilingiris Dimitrios , Mooshage Christoph M , Kender Zoltan , Sulaj Alba , von Rauchhaupt Ekatherina , Szendroedi Julia , Herzig Stephan , Goepfert Jens , Groener Jan , Nawroth Peter P , Bendszus Martin , Heiland Sabine , Kurz Felix T , Jende Johann M E , Kopf Stefan
Published: January 2024

Context

Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routines, leading to increased morbidity and mortality.

Objective

We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory, and physical markers of DPN to evaluate PhA as a possible diagnostic method for DPN.

Materials and methods

In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications, we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), among which 63 had DPN. The PhA was calculated from multifrequency BIA. Nerve conduction studies, quantitative sensory testing (QST) and diffusion-weighted magnetic resonance neurography to determine fractional anisotropy (FA) reflecting peripheral nerve integrity were performed.

Results

T2D patients with DPN had lower PhA values (5.71 ± 0.10) compared to T2D patients without DPN (6.07 ± 0.08, P = .007, + 6.1%) and healthy controls (6.18 ± 0.08, P < .001, + 7.9%). Confounder-adjusted analyses showed correlations of the PhA with conduction velocities and amplitudes of the peroneal (β=.28; β=.31, P < .001) and tibial nerves (β=.28; β=.32, P < .001), Z-scores of QST (thermal detection β=.30, P < .05) and the FA (β=.60, P < .001). Receiver-operating characteristic analysis showed similar performance of PhA in comparison to the mentioned diagnostic methods.

Conclusion

The study shows that PhA is, in comparison to other test systems used, at least an equally good and much easier to handle investigator-independent marker for detection of DPN.
P-01 Case report of adrenal insufficiency due to bilateral adrenal hemorage
Authors: Korkmaz Elif Seray , Gökçe Birsen Öztürk , Nur Kebapçı Medine , Yorulmaz Göknur
Published: January 2024

Introduction

Arterial or venous thrombosis may be seen in the presence of antiphospholipid antibody (AFA). Rarely, it can cause adrenal hemorrhage. In this case, a 39-year-old case of adrenal insufficiency due to adrenal hemorrhage accompanied by AFA is presented.

Clinical Case

A 39-year-old male patient with no known disease was admitted to the emergency service with complaints of abdominal pain, general condition disorder, weakness, nausea and vomiting. Hypotension, Na:121meq/L (136-145 meq/L) and K:6.2 meq/L (3.5-5 meq/L), creatinine: 3.56 mg/dl (0.7-1.20), urea: 50.5 mg /dl (6-20), cortisol value measured by suspecting acute adrenal insufficiency was 1.42 µg/dL (5-25 µg/dL), ACTH value was 561 pg/mL (10-46 pg/mL). Abdominal CT for abdominal pain showed a collection area of 58 mm ap diameter on the right and 66 mm ap diameter on the left in both surrenal lobes, and numerous millimeter-sized hypointense areas in the subcapsular area of both kidneys and were evaluated as significant in terms of microinfarcts. Then, areas that were hyperdense in the precontrast series and did not show significant enhancement in the postcontrast series were evaluated for bleeding in adrenal CT (Figure 1).In the tests performed, aPTT 44.5 sec (24-40), C3 1.272 g/dL (0.9-1.8 g/dL), ANA:1/160 homogeneous positive granular, anti-dsDNA:28 IU/mL, lupus anticoagulation positive, in complete urinalysis proteinuria and hyaline cast were detected. The patient was diagnosed with AFAS and systemic lupus erythematosus (SLE), and hydroxychloroquine was started. Warfarin and acetylsalicylic acid were started due to renal vein thrombosis. Stress-dose steroid therapy (80 mg/day methylprednisolone) was started in the patient who was suspected of having adrenal insufficiency due to adrenal hemorrhage. The hemorrhage in our patient was attributed to the hemorrhage caused by the AFA-related infarction. The patient who completed the treatment was discharged with 200 mg hydroxychloroquine, 30 mg hydrocortisone, 0.5 mg fludrocortisone, 5 mg warfarin, 100 mg acetylsalicylic acid, 10 mg amlodipine.

Conclusion

Although the pathogenetic mechanism of adrenal insufficiency seen in AFA syndrome is not fully known; increased coagulation status in these patients is held responsible. Adrenal insufficiency is thought to be due to hemorrhage after venous thrombosis at the adrenal vein or microvascular level. AFA-related adrenal insufficiency is usually permanent and rarely resolves. Therefore, long-term follow-up of these patients is required. The presence of AFA should be investigated in patients presenting with bilateral adrenal hemorrhage.Figure 1.Sürrenal bt
P-03 A report of recurring pregnancy-induced Cushing's Syndrome
Authors: Niafar Mitra , Bahrami Amir , Ghorbani Fatemeh , Aghamohammadzadeh Naser , Sadra Vahideh , Djala Nader Nader
Published: January 2024

Introduction

The incidence of pregnancy-induced Cushing's syndrome (CS) is very low. However, the diagnosis of CS in pregnant patients is very difficult because of an overlapping signs and symptoms.

Clinical Case

A 20-year-old woman with polycystic ovarian syndrome (PCOS) was successfully treated with clomiphene for infertility and pregnant in September of 2016 for the first time. She experienced out of proportion abdominal obesity, excessive striosis, exacerbation of hirsutism and myasthenia during the first trimester of her pregnancy. Initial diagnosis of ovarian hyperstimulation syndrome (OHSS) was made and due to concomitant intrauterine growth retardation (IUGR), the pregnancy was electively terminated at the 8th week. All associated symptoms spontaneously regressed within 2-3 months after the abortion. The second pregnancy was induced with a pulse treatment of letrozole 5 mg, followed by 3 every other day injections of 100 units recombinant follicle-stimulating hormone. Within the first 4 weeks into the second pregnancy, the patient developed recurrence of OHSS symptoms. In addition to the prior symptoms and progressive proximal myasthenia, the patient developed hypertension, round moon-like face, back hump, and suprasternal fat pad consistent with the typical features of CS. In week 14 of pregnancy, the patient complained from acute-onset bilateral blindness and hypertension (blood pressure of 180/120 mmHg), which soon progressed into loss of consciousness and grand-mal seizure. She was admitted to the intensive care unit (ICU). Admission laboratory testing included those to assess the function of the pituitary-adrenal axis (HPA) due to the presence of symptoms related to CS. Based on available clinical information a diagnosis of hemolysis, elevated liver enzymes, and a low platelet count (HELLP) syndrome was made and emergency termination of pregnancy was carried out at the gestational age of 14 weeks. The patient`s clinical signs such as hypertension and acute blindness were totally subsided soon after the therapeutic abortion. Diagnosis of ACTH independent CS was made based on elevated 8 a.m. serum cortisol level unresponsive to low-dose dexamethasone (45-41 µg/ dL).

Conclusion

Diagnosis of CS in pregnancy is challenging as the physiological changes during pregnancy may mimic those of CS. Long-term treatment of gestational CS has not been as successful. However, in the case of adrenal hyperplasia, bilateral adrenalectomy offers a certain cure. Our patient had a therapeutic abortion due to severe maternal complications and development of CS during the early gestational age. The patient was reeducated on the subject of contraception and the possibility of adrenalectomy for future pregnancies. Due to the temporal relation between the occurrence of CS after each pregnancy the diagnosis of gestational hypercortisolism was made, and for further pregnancies bilateral adrenalectomy was recommended.
P-06 Catecholamine-induced cardiomyopathy: A rare presentiation of pheochromocytoma
Authors: Bağır Gülay Şimşek , Haydardedeoğlu Fi̇li̇z , Bakiner Okan , Yabanoğlu Hakan , Torun Neşe , Koçer Emrah , Gürkan Hakan , Ertörer Melek Eda
Published: January 2024

Introduction

Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors. Clinical manifestations consist of various cardiovascular signs and symptoms related to excessive secretion of catecholamines. Catecholamine-induced cardiomyopathy is a rare but life-threatening complication of PPGL. Excessive discharge of catecholamines results in vasoconstriction, coronary vasospasm and myocardial ischemia. Three types of cardiomyopathies can be observed in patients with PPGL; dilated cardiomyopathy, Takotsuba cardiomyopathy and hypertrophic cardiomyopathy.

Clinical Case

Herein, we present a case with PPGL complicated with heart failure probably due to excessive secretion of catecholamines. A 19 years-old man was admitted to emergency department with dyspnea and hypotension. He exhibited severe signs of heart failure with very high liver function tests; ALT: 3647 U/L (8-65) and AST: 4542U/L (7-40), probably due to hepatic congestion. Echocardiogram performed in ICU reported %10 left venticular ejection fraction with diffuse akinesia. Remarkable improvement of liver function was recorded following the introduction of heart failure medicines. A computed tomography scan that was performed for abdominal pain and distension revealed a six cm tumour at the left adrenal gland compatible with pheochromocytoma. Laboratory analyses were; 24-hour urine metanephrines: 1938mcg (44-261), normetanephrines: 17934mcg (103-390). Following necessary preoperative preparations, laparoscopic left adrenalectomy was performed and a 70 mm adrenal tumor, histopathologically compatible with pheochromocytoma, was excised. His postoperative laboratory findings were; 24-hour urine metanephrines: 248 mcg (44-261), normetanephrines: 4368 mcg (103-390), chromogranin A: 554.9 ng/ml (0-100), 3-methoxytyramine: 0.34 nmol/l (0-0.17). A 68-Ga-DOTA-Peptide PET/CT following 12 weeks of surgery demonstrated hypermetabolic lesions at left suprarenal area. A second open surgery was performed and lymph node metastases were detected (Figure 1). His cardiac functions ameliorated significantly following the removal of tumors. Genetic analysis for PPGL syndromes were negative for KIF1B, SDHB, NTRK1, TMEME127, VHL, RET, SDHD genes. Work-up is still pending for the mutations of SDHA, SDHC and SDHAF2 genes.

Conclusion

Cathecolamine-induced cardiomyopathy is a rare entity associated with PPGL. Urgent recognition of related clinical signs and symptoms and detection of PPGL is lifesaving. It should be kept in mind in patients presenting with symptoms of heart failure, hypotension and multisystem crisis in the absence of coronary or valvular heart disease.Figure 1.Pheochromocytoma with lymph node metastasis. (H&E x100)