bluuebunny/crossref_metadata_2025 huggingface dataset:
Could TREM-1 be a novel marker in the diagnosis of fibromyalgia?: A cross-sectional study
Authors: Aydogan Baykara Rabia , Kiran Tuğba Raika , Otlu Önder , Erdem Mehmet , Pihtili Taş Nevsun
Published: July 2024

Triggering receptors expressed on myeloid cells-1 (TREM-1) are transmembrane molecules expressed in cells of the immune system. Activation of TREM-1 leads to the release of pro-inflammatory mediators, which act as amplifiers of inflammation and thereby contribute to the pathogenesis of various diseases, whether inflammatory or not. This study explored the role of TREM-1 in the etiopathogenic context of fibromyalgia syndrome (FMS) and its association with disease activity. This randomized controlled and observational study included 45 patients diagnosed with FMS according to the 2016 American College of Rheumatology criteria. Serum TREM-1 levels were assessed using ELISA, and disease activity was measured using various scales such as the fibromyalgia impact questionnaire (FIQ). Patients were divided into 2 groups according to disease severity based on the FIQ score. Compared to a control group of 46 healthy individuals, patients with FMS exhibited significantly elevated concentrations of TREM-1 (mean ± SD = 216.97 pg/mL ± 16.04), P < .05. The FIQ, Pittsburgh sleep quality index, hospital anxiety and depression scale, fatigue severity scale, and visual analog scale, which confirm symptoms such as pain, disease severity, sleep disturbance, depression, anxiety, and fatigue seen in FMS was significantly correlated with TREM-1 level (P < .001). The optimal threshold value for TREM-1 to disease activity was determined to be 182.250, showing (area under the curve) (CI (95%)): [0.940] (0.887–0.993), a sensitivity of 97% and a specificity of 89% according to the receiver operating characteristic analysis. The positive correlation of TREM-1 with various symptom severity scales and hematological inflammatory indices may be a suitable biomarker for the diagnosis of FMS and a potential therapeutic target.
Endoscopic full-thickness resection of a large gastric schwannoma and iatrogenic cervical esophageal perforations: A case report
Authors: Huang Siying , Huang Sifu , Fang Taiyong
Published: July 2024

Introduction:

Gastrointestinal schwannomas are most commonly found in the stomach. Owing to their nonspecific clinical and endoscopic presentations, distinguishing gastric schwannomas (GS) from other gastric submucosal tumors based on typical symptoms and endoscopic features is challenging. Endoscopic full-thickness resection (EFTR) is safe and effective for GS management; however, no standard method exists for the extraction of large gastric specimens after endoscopic treatment.

Case presentation:

We report the case of a 72-year-old Chinese woman who presented with abdominal distension.

Diagnosis, interventions, and outcomes:

Gastroscopy revealed a submucosal bulge on the anterior wall of the lower stomach near the greater curvature. Endoscopic ultrasonography and computed tomography suggested a stromal tumor. The patient underwent EFTR of the stomach, and the tumor was successfully removed. The surgical specimen, with a long-axis diameter of approximately 5.5 cm in vitro, was extracted using a snare. Subsequent endoscopic examination revealed longitudinal, full-thickness perforations > 2 cm at the esophageal entrance. Over 10 metal clips were used to seal the mucosa, and a gastrointestinal decompression tube was placed. Follow-up radiography performed at 1 week postoperatively revealed an esophageal mediastinal fistula, which required subsequent endoscopic intervention to close the fistula using metal clips. The patient showed improvement and was discharged at 3 weeks postoperatively. Follow-up esophageal radiography revealed no abnormalities. Postoperative immunohistochemical analysis indicated CD34 (−), CD117 (−), DOG-1 (−), Ki67 (1%), S-100 (+), SDHB (+), SOX-10 (+), and Desmin (−), confirming the diagnosis of GS. Three months postoperatively, gastroscopy showed that the esophageal perforation healed well, a white ulcer scar had formed locally, metal clips were found in the stomach body, and no recurrence was found.

Conclusion:

EFTR is effective for removing giant schwannomas, although the extraction of large specimens may result in iatrogenic cervical esophageal perforations. Perforations > 2 cm can be managed using endoscopic metal clip closure.
The causal relationship of depression, anxiety, and neuroticism with endometriosis: A bidirectional 2-sample Mendelian randomization study
Authors: Zhang Jiaxun , Li Tie , Zhao Jinying , Chai Jiapeng , Wang Lin , Cao Wenxuan , Liu Jia , Wang Fuchun
Published: July 2024

Endometriosis, identified by the abnormal growth of endometrial cells beyond the inner lining of the uterus, often manifests through symptoms like painful menstruation and challenges in conceiving. Observational studies suggest that endometriosis is often comorbid with mental disorders, including anxiety and depression. The nature of these connections, whether they are causal, is still debated and calls for further empirical evidence. We utilized a bidirectional 2-sample Mendelian randomization (MR) approach, harnessing genome-wide association study data to explore the connections among depression, anxiety, neuroticism, and endometriosis. To scrutinize the causative connections between mental health issues and endometriosis, Inverse Variance Weighting (IVW) was employed as the primary analytical tool, complemented by Weighted Median Estimation, Simple mode, Weighted mode, and MR-Egger regression for additional analysis. To examine the potential for reverse causation, reverse MR was applied. To strengthen the reliability of our findings, we carried out sensitivity analyses that included heterogeneity tests, tests for pleiotropy, and leave-one-out analyses. The IVW analysis revealed a significant correlation between the genetic inclination towards depression and a heightened risk of developing endometriosis [Odds Ratio (OR) = 1.151, 95% Confidence Interval (CI) = 1.025–1.293, P = .017]. Similarly, a genetic predisposition to neuroticism was significantly associated with an increased risk of endometriosis (OR = 1.128, 95% CI = 1.038–1.226, P = .004). However, no causative link was found between genetic susceptibility to anxiety and the occurrence of endometriosis. Reverse MR analysis did not support a bidirectional genetic susceptibility between endometriosis and psychiatric disorders. The MR analysis presents genetic data supporting the notion that depression and neuroticism are risk factors for endometriosis. Conversely, it found no evidence of a causal connection between anxiety and the development of endometriosis. Enhancing mental health treatment should be considered a preventive measure against endometriosis.
Oral amiodarone and propranolol in maintenance therapy of postimplantation tachycardia: An observational study
Authors: Arslan Abdulla , Özkaya Öykü Gülmez , Aytemiz Fatih , Altay Hakan , Özcan Emin Evren , Küçükaksu Deniz Süha , Bakuy Vedat , Kozan Ömer , Pehlivanoğlu Seçkin
Published: July 2024

Left ventricular assist devices (LVADs) are widely used as end-stage therapy in patients with advanced heart failure, whereas implantation increases the risks of development of sustained ventricular tachycardia at the later postimplantation stage. Therefore, this study aimed to evaluate the clinical efficacy of orally administered amiodarone and propranolol in 3 patients with ventricular tachycardia (VT) after LVAD implantation who were resistant to initial anti-antiarrhythmic drugs. This retrospective cohort study consisted of the initial evaluation of the clinical data of 14 adult patients who underwent implantation of LVAD between January 2019 and March 2021. A total of 3 patients with resistant VT were finally included. In all cases, the patients were initially administered amiodarone in the different doses intravenously to stabilize the critical condition, whereas its oral form along with that of propranolol was used as maintenance therapy in the first 2 cases. In the third case, amiodarone was withdrawn because of the risk of development of hyperthyroidism, while oral propranolol was used in the treatment. The assessment in the 16-month follow-up period after discharge did not show presence of non-sustained and sustained VT in all 3 cases. In the ventricular arrhythmia-free group, the total mortality rate within the follow-up period was 11.1 ± 7.78 months in the 3 patients. We suggest that maintenance oral therapy of propranolol and amiodarone can significantly decrease the risks of complications in patients with VT after implantation of ventricular assist device in the long term.
Association between serum selenium and non-alcoholic fatty liver disease: Results from NHANES: An observational study
Authors: Liu Yajie , Wang Ruilin
Published: July 2024

Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of diseases and stands as the second most prevalent liver disorder in the 21st century. Advanced hepatic fibrosis (AHF) is a crucial indicator of the progression of NAFLD. Selenium (Se) is an indispensable trace element for human physiology; however, excessive intake can lead to poisoning and detrimental effects. Notably, males exhibit significantly higher serum Se levels compared to females. To investigate the correlation between serum Se levels and the prevalence of NAFLD and AHF across different genders. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 2017–2020, 7271 participants were included. Through descriptive analysis, multivariable logistic regression, subgroup analysis, interaction, and restricted cubic spline regression analysis, the relationship between serum Se levels and the prevalence of NAFLD and AHF was investigated. serum Se levels were significantly higher in both male and female NAFLD groups compared to the non-NAFLD groups (Males: 187.570 vs 183.300, Z = −16.169, P < .001; Females: 184.780 vs 180.130, Z = −4.102, P < .001). After adjusting for confounders, an increase in one quartile of serum Se was associated with a 17.60% increase in NAFLD prevalence in males (OR, 1.176; 95% CI: 1.052–1.315) and a 38.50% decrease in AHF prevalence (OR, 0.615; 95% CI: 0.479–0.789). In females, each quartile increase in serum Se was associated with a 29.10% increase in NAFLD prevalence (OR,1.291;95%CI: 1.155–1.442) and a 51.60% decrease in AHF prevalence (OR, 0.484; 95% CI: 0.344–0.682). serum Se levels are positively correlated with the prevalence of NAFLD and negatively correlated with the prevalence of AHF in both males and females.
DNA methylation analysis in plasma for early diagnosis in lung adenocarcinoma
Authors: Jin Yulin , Lu Rongguo , Liu Feng , Jiang Guanyu , Wang Ruixin , Zheng Mingfeng
Published: July 2024

Background:

Lung adenocarcinoma (LUAD) represents the most prevalent type of lung cancer. SHOX2 and RASSF1A methylation have been identified as important biomarkers for diagnosis and prognosis of lung cancer. Bronchoalveolar lavage fluid (BALF) exhibits good specificity and sensitivity in diagnosing pulmonary diseases, but its acquisition is challenging and may cause discomfort to patients. In clinical, plasma samples are more convenient to obtain than BALF; however, there is little research on the concurrent detection of SHOX2 and RASSF1A methylation in plasma. This study aims to assess the diagnostic value of a combined promoter methylation assay for SHOX2 and RASSF1A in early-stage LUAD using plasma samples.

Methods:

BALF and blood samples were obtained from 36 early-stage LUAD patients, with a control group of nineteen non-tumor individuals. The promoter methylation levels of SHOX2 and RASSF1A in all subjects were assessed using the human SHOX2 and RASSF1A gene methylation kit.

Results:

The methylation detection rate of SHOX2 and RASSF1A in plasma was 61.11%, slightly lower than that in BALF (66.7%). The Chi-square test revealed no significant difference in the methylation rate between BALF and plasma (P > 0.05). The area under the receiver operating characteristic (ROC) curve analysis for blood was 0.806 (95% CI, 0.677 to 0.900), while for BALF it was 0.781 (95% CI, 0.649 to 0.881). Additionally, we conducted an analysis on the correlation between SHOX2 and RASSF1A methylation levels in plasma with gender, age, tumor differentiation, pathologic classification, and other clinicopathological variables; however, no significant correlations were observed.

Conclusions:

Measurement of SHOX2 and RASSF1A methylation for early diagnosis of LUAD can be achieved with high sensitivity and specificity by using plasma as a substitute for BALF samples.
Association between financial hardship and psychological burden and the role of social and mental health support: An observational study
Authors: Jung Jinho , Mukherjee Kumar , Brown Mary , Sadigh Gelareh
Published: July 2024

We aimed to assess the association between medical financial hardship and psychological burden and the moderating role of social and mental health support. 2021 United States National Health Interview Survey was used. Financial hardship was defined as having financial worry, material hardship, or cost-related care nonadherence. Psychological burden was measured using perceived general health status, satisfaction with life, and serious psychological distress (SPD). Of 29,370 included adults, 49% experienced financial hardship in the last 12 months. Financial hardship was associated with a higher psychological burden (odds ratio [OR], 3.58; 95% confidence interval [CI], 2.43–5.47 for SPD). Eleven percent received counseling/therapy from mental health professionals, and 90% had experienced frequent social support. Frequent social support was associated with lower financial hardship (OR, 0.71; 95% CI, 0.63–0.80) and psychological burden (OR, 0.28; 95% CI, 0.19–0.42 for SPD). Previous mental health support was associated with higher financial hardship (OR,1.40; 95% CI, 1.28–1.54) and psychological burden (OR, 9.75; 95% CI, 6.97–13.94 for SPD). Those experiencing financial hardship had lower odds of SPD if they received mental health support in the last 12 months (OR, 0.57; 95% CI, 0.39–0.85). Future interventions should also focus on improving social support and mental health for patients as a way of mitigating medical financial hardship.
Celiac trunk aortic dissection induced by bevacizumab therapy for rectal cancer: A case report
Authors: Su Mingming , Zhao Lili , Zhou Jing , Li Xuan , Ding Ning
Published: July 2024

Rationale:

Bevacizumab (Bev) is a humanized monoclonal antibody that targets vascular endothelial growth factor A and is primarily used for the treatment of various solid tumors. Aortic dissection (AD) is a severe vascular disease caused by the tearing of the intimal layer of the aorta or bleeding within the aortic wall, resulting in the separation of different layers of the aortic wall. However, the pathogenesis is not fully understood. Some studies have suggested that Bev treatment is associated with the occurrence of AD.

Patient concerns:

A 67-year-old Chinese male was diagnosed with rectal cancer accompanied by liver and lung metastasis. Three days after starting combined chemotherapy with Bev, the patient developed persistent abdominal pain. Abdominal CT scan revealed celiac trunk AD in the abdominal aorta.

Diagnoses:

The patient was diagnosed with rectal cancer accompanied by liver and lung metastases. Abdominal CT tomography revealed a celiac trunk AD.

Interventions:

Somatostatin combined with valsartan was used to control blood pressure. The patient was subsequently referred for vascular surgery and underwent an abdominal aortic angiography. Conservative treatment was continued.

Outcomes:

Three months after the initiation of treatment, follow-up abdominal CT scans showed stability in the condition of celiac trunk AD, with no abdominal pain or hypertension. There were no signs of worsening dissection, aneurysm formation, or inadequate perfusion of end organs.

Lessons:

There may be a connection between Bev and elevated blood pressure as well as celiac trunk AD.
Endovascular treatment for 2 types of subclavian artery injury: A case report
Authors: Kim Gun Woo , Hwang Suyeong , Lim Kyoung Hoon , Cho Sung Hoon
Published: July 2024

Rationale:

Subclavian artery (SCA) injuries, though rare, carry significant morbidity and mortality risks due to significant blood loss causing hypovolemic shock. Early diagnosis and adequate treatment are crucial to minimize bleeding and associated morbidity. Recent advances in endovascular techniques offer faster and more accurate treatment options compared to traditional open surgical repair. This study demonstrates the efficacy of endovascular treatment in 2 cases of SCA injury and reviews its indications, limitations, and precautions.

Patient concerns:

A 69-year-old man presented with a penetrating SCA injury from a steel bar, and a 38-year-old woman presented with a blunt SCA injury caused by a fall. Both patients were hemodynamically unstable upon presentation.

Diagnoses:

Both patients were diagnosed with SCA injuries. The man had a penetrating injury, while the woman had a blunt injury, both resulting in hemodynamic instability and significant risk of hypovolemic shock.

Interventions:

Endovascular techniques, including the use of covered stent grafts, were employed to manage the injuries. These techniques allowed for rapid and efficient treatment, reducing the need for open surgical intervention.

Outcomes:

Both patients were successfully treated using endovascular methods and were discharged without any complications. The endovascular approach minimized blood loss, transfusion needs, and hospital stay.

Lessons:

This study demonstrates the effectiveness of endovascular techniques in rapidly diagnosing, bridging, and definitively treating SCA injuries, suggesting their use as a first-line therapy.
Application of m6A regulators to predict transformation from myelodysplastic syndrome to acute myeloid leukemia via machine learning
Authors: Ma Jichun , Zhao Hongchang , Ge Fang
Published: July 2024

Myelodysplastic syndrome (MDS) frequently transforms into acute myeloid leukemia (AML). Predicting the risk of its transformation will help to make the treatment plan. Levels of expression of N6-methyladenosine (m6A) regulators is difference in patients with AML, MDS, and MDS transformed into AML. Seven machine learning algorithms were established based on all of 26 m6A or main differentially expressed m6A regulator genes, and attempted to establish a risk assessment method to distinguish AML from MDS and predict the transformation of MDS into AML. In collective of m6A regulators sets, support vector machine (SVM) and neural network (NNK) model best distinguished AML or MDS from control, with area under the ROC curve (AUROC) 0.966 and 0.785 respectively. The SVM model best distinguished MDS from AML, with AUROC 0.943, sensitivity 0.862, specificity 0.864, and accuracy 0.864. In differentially expressed gene sets, SVM and logistic regression (LR) model best distinguished AML or MDS from control, with AUROC 0.945 and 0.801 respectively. The random forest (RF) model best distinguished between MDS and AML, with AUROC 0.928, sensitivity 0.725, specificity 0.898, and accuracy 0.818. For predictive capacity of MDS transformed into AML, SVM model showed the best predicted in collective m6A regulators sets, with AUROC 0.781 and accuracy 0.740. The LR model showed the best predicted in differential expression m6A regulators sets, with AUROC 0.820 and accuracy 0.760. All results suggested that machine learning model established by m6A regulators can be used to distinguished AML or MDS from control, distinguished AML from MDS and predicted the transformation of MDS into AML.
Enhancing treatment of lumbar disc herniation with Erxian decoction and auricular acupoint pressure: A randomized controlled trial
Authors: Feng Wei , Du Xixi , Zhao Yuxin
Published: July 2024

Objective:

The incidence of lumbar disc herniation (LDH) is on the rise annually, with an emerging trend of affecting younger age groups. This study aims to investigate the clinical effectiveness of combining Erxian decoction with auricular acupoint pressure therapy in treating LDH. Our objective is to furnish evidence supporting the incorporation of traditional Chinese medicine (TCM) rehabilitation techniques in clinical settings.

Methods:

This randomized controlled trial enrolled 102 patients diagnosed with LDH and allocated them into Control and Intervention groups. The Control group underwent a 2-week rehabilitation regimen, whereas the Intervention group received an augmented treatment comprising Erxian decoction along with auricular acupoint pressure therapy based on the Control group. Main outcome measures included 3 scales – visual analog scale (VAS), Japanese Orthopedic Association (JOA), and Oswestry Disability Index – as well as 3 inflammatory markers: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Additionally, pressure pain threshold and pain tolerance threshold values were evaluated. Participants were assessed at baseline, on 14-day, and on 28-day posttreatment.

Results:

After 2 weeks of treatment, both the Control and Intervention groups exhibited significant improvements in the VAS, JOA, ODI, CRP, IL-6, TNF-α, pressure pain threshold, and pain tolerance threshold (P < .05). These improvements persisted at the 28-day in the VAS, JOA, and ODI scores (P < .05). On 14-day, the Intervention group showed significantly better outcomes compared to the Control group in terms of the VAS, JOA, ODI, CRP, TNF-α, and pressure pain threshold (P < .05).

Conclusion:

Compared to conventional rehabilitation therapy, the combination of Erxian decoction and auricular acupoint pressure therapy demonstrates clear benefits in alleviating symptoms in patients with LDH. This approach offers fresh perspectives and substantiates evidence for future treatment strategies in managing LDH.
Stanniocalcin-2 expression in glioblastoma – A novel prognostic biomarker: An observational study
Authors: Aydin Asim Armagan , Yildirim Senay
Published: July 2024

The objective of this study was to assess the prognostic relevance of Stanniocalcin-2 (STC2) expression, as determined via immunohistochemistry in tumor tissue, in a cohort of 83 patients diagnosed with glioblastoma who underwent maximal safe surgical resection followed by radiotherapy concurrent with adjuvant temozolomide. STC2 expression levels were categorized using a 3-tiered semiquantitative system: negative expression (level 0−), low expression (level 1+), and high expression (levels 2 + and 3+). Patients were categorized into 2 distinct groups according to their STC2 expression levels: negative STC2 (−/+) and positive STC2 (++/+++). The primary outcome measure was the relationship between STC2 expression and progression-free survival (PFS), with overall survival (OS) serving as the secondary endpoint. Kaplan–Meier survival analysis confirmed that patients exhibiting high STC2 expression had significantly shorter OS (8 vs 20 months, P < .001) and PFS (6 vs 18 months, P < .001) than those with low or negative STC2 expression. Multivariate analysis revealed that STC2 expression was an independent prognostic factor for both OS (hazard ratio: 0.4; 95% confidence interval: 0.2–0.8; P < .05) and PFS (hazard ratio: 0.3; 95% confidence interval: 0.2–0.4; P < .05) in patients with glioblastoma. Furthermore, elevated STC2 expression in GBM was correlated with several established aggressive clinicopathological characteristics, including advanced age (≥65 years), low ECOG PS (≥2), and isocitrate dehydrogenase mutation negativity. These findings underscore that heightened STC2 expression within the tumor tissue of GBM patients functions as an adverse prognostic marker, correlating with an elevated risk of progression and reduced OS. Therapeutic interventions targeting the AKT-mTOR, ERK1-2, and mitogen-activated protein kinase pathways as well as immune checkpoint inhibitors and vascular endothelial growth factor blockade, as well as potential forthcoming antibody–drug conjugates targeting the STC2 molecule, have the potential to broaden the scope of combined treatment strategies.
Significance of family history of cholelithiasis in a Pakistani population: A single center, descriptive cross-sectional study
Authors: Ali Mansab , Usman Amir , Usman Javeria , Abid Muhammad , Najeeb Wafa , Imran Muhammad , Fakih Nour
Published: July 2024

Linkage studies have indicated a potential genetic predisposition to cholelithiasis. This study aims to determine the frequency of positive family history of gallstone disease in patients presenting with gallstones in a Pakistani population. A descriptive, cross-sectional study was conducted at the surgical department of the University of Lahore Teaching Hospital from June 30, 2023 to August 30, 2023. A total of 102 radiologically confirmed cholelithiasis patients were enrolled. Out of 102 participants, 75.5% (n = 77) were females, with a mean age at presentation of 42.1 ± 12.1 years. The study found that 32.4% (n = 33) of participants had a single family member with gallstones, 3.9% (n = 4) had 2 family members affected, and 1% (n = 1) had 3 family members affected. The attributable risk of genetics from our study was 37.2%. Additionally, there was no significant association between positive family history and earlier onset of disease. A significant percentage of Pakistani population may have gallstone disease due to genetic factors.
The evolution of ancient healing practices: From shamanism to Hippocratic medicine: A review
Authors: Elendu Chukwuka
Published: July 2024

In the ever-evolving healthcare landscape, ancient healing traditions cast a profound shadow, offering insights and inspirations that resonate with modern medical practice. This paper explores the enduring influence of shamanic and Hippocratic healing traditions on contemporary healthcare, examining their contributions to holistic health approaches, diagnostic techniques, and ethical standards. The Hippocratic emphasis on observation, clinical experience, and ethical principles laid the foundation for modern Western medicine, while shamanic practices highlight the importance of spiritual and psychological dimensions in healing. The comparative analysis reveals both commonalities and distinctions among various ancient practices, such as Ayurveda, Traditional Chinese Medicine, and indigenous healing systems, emphasizing their holistic understanding of health and the use of natural remedies. Cross-cultural exchanges, from the Silk Road to the Islamic Golden Age and beyond, facilitated the integration and dissemination of medical knowledge, enriching global medical traditions. The paper also discusses the impact of these ancient practices on contemporary healthcare systems, highlighting the resurgence of holistic and integrative medicine, the validation and incorporation of herbal remedies, and the challenges of cultural appropriation and scientific validation. By embracing the wisdom of ancient healing traditions and fostering collaboration between traditional and modern medicine, contemporary healthcare can enhance therapeutic options, promote patient-centered care, and address global health challenges with a more inclusive and compassionate approach. This integration holds promise for the future of healthcare, benefiting individuals and communities worldwide.
Efficacy and safety of resmetirom among patients with non-alcoholic steatohepatitis: a systematic review and meta-analysis
Authors: Mazhar Saad , Azhar Aima , Khan Ariba , Shakil Gulrukh , Kumari Sapna , Devi Deepa , Jawad Sayed
Published: July 2024

Background:

Non-alcoholic steatohepatitis (NASH) is a severe medical illness that has few available therapeutic options. Resmetirom, a liver-targeting agonist of the thyroid hormone receptor (THR), has recently been licenced by the FDA. We assess the effectiveness and safety of resmetirom in patients with NASH.

Methods:

PubMed, SCOPUS and Cochrane Central were searched till March 2024 to find potential articles. Outcomes assessed included MRI-proton density fat fraction (MRI-PDFF), Fat Reduction, and NASH Resolution Without Fibrosis, changes in aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), low-density lipoprotein (LDL), and triglyceride (TG) levels, along with diarrhoea, nausea, urinary tract infection (UTI), and headache. Subgroup analysis was performed between outcomes before and after 6 months. Outcomes were analyzed with a random-effects model and results presented as mean difference (MD) for continuous outcomes and odds ratios (OR) for safety analysis, along with their 95% confidence intervals. A risk of bias assessment was performed using Cochrane Risk of Bias tool.

Results:

Four randomized controlled trials (RCTs) were included in our analysis. Resmetirom shown a substantial improvement in MRI-PDFF with a MD of −19.23 (P<0.00001). Additionally, it resulted in a 30% reduction in fat (OR: 3.54, P=0.004) and resolution of NASH without fibrosis (OR: 2.41, P=0.04). There was no notable enhancement observed in AST levels, with a mean difference of −0.87 and a P value of 0.73. The usage of resmetirom resulted in significant improvement in ALT levels (MD: −4.36, P value: 0.32), GGT levels (MD: −17.87, P value: <0.00001), TG levels (MD: −23.48, P value: <0.00001), LDL levels (mean difference: −12.80, P value: <0.00001), and rT3 levels (MD: -2.08, P value: <0.00001). The use of Resmetirom was associated with a higher likelihood of experiencing diarrhoea (OR: 2.07, P<0.0001) and nausea (OR: 1.81, P=0.0003). However, there was no significant difference observed in the occurrence of UTI (OR: 1.04, P=0.85) or headaches (OR: 0.79, P=0.48).

Conclusion:

Resmetirom demonstrates efficacy in enhancing MRI-PDFF score, diminishing adipose tissue, resolving NASH without fibrosis, reducing GGT, TG, LDL, reverse triiodothyronine (rT3) levels in NASH patients. Nevertheless, there is also an observed heightened susceptibility to experiencing diarrhoea and nausea. Additional trials are necessary to further examine the efficacy and safety of this medication.
Predictors of quality of life, economic impact, and loss to follow-up after open tibial shaft fractures in Ghana
Authors: Ativor Vincent , Konadu-Yeboah Dominic , O'Marr Jamieson , Brown Kelsey , Rodarte Patricia , Kumah Ralph , Quartey Ralph , Awariyah Dominic , Konadu Peter , Baidoo Paa Kwesi , Okike Kanu , Morshed Saam , Shearer David , Roberts Heather
Published: July 2024

Objectives:

Open tibia fractures are associated with substantial morbidity and impact on quality of life. Despite increasing incidence in low-resource settings, most open tibia fracture research comes from high-resource settings. This study aimed to assess the impact of socioeconomic status on treatment modality and evaluate predictors of health-related quality of life following open tibia fractures in Ghana.

Design:

A single-center prospective observational study was conducted in Kumasi, Ghana, from May 2020 to April 2022. Adults with open tibial shaft fractures presenting within 2 weeks of injury were eligible. Demographics, comorbidities, socioeconomic factors, and hospital course were collected at enrollment. Follow-up was scheduled at 8, 12, 26, and 52 weeks. A telephone survey assessing reasons for loss to follow-up was initiated on enrollment completion.

Results:

A total of 180 patients were enrolled. Most patients were employed before injury (79.9%), had government insurance (67.2%), and were from rural areas (59.4%). Fracture classification was primarily Gustilo–Anderson type 3A (49.1%). No relationship between socioeconomic predictors and treatment modality was identified. The largest barriers to follow-up were preference for bonesetter treatment (63.1%), treatment cost (48.8%), and travel cost (29.8%). Of the lost to follow-up patients contacted, 67 (79.8%) reported receiving traditional bonesetter care. Reasons for seeking traditional bonesetter care included ease of access (83.6%), lower cost (77.6%), and familial influence (50.7%).

Conclusion:

No association was identified between socioeconomic predictors and choice of treatment. Bonesetter treatment plays a substantial role in the care of open tibia fractures in Ghana, largely because of ease of access and lower cost.
Analysis of Surgeon and Center Case Volume and Stroke or Death after Transcarotid Artery Revascularization
Authors: Elsayed Nadin , Khan Maryam Ali , Janssen Claire B , Lane John , Beckerman William E , Malas Mahmoud B
Published: July 2024

BACKGROUND:

It has been suggested that the annual hospital volume of cases may affect the number of adverse events after carotid endarterectomy (CEA). We aim to study the associations between hospital as well as surgeon volume and the risk of stroke or death after transcarotid artery revascularization (TCAR).

STUDY DESIGN:

Retrospective review of the Vascular Quality Initiative data of patients undergoing TCAR from 2016 to 2021. Surgeon and center volume were calculated based on the mean number of cases (MNC) performed yearly by each surgeon and center. The primary outcome was a composite endpoint of in-hospital stroke or death.

RESULTS:

A total of 22,624 cases were included. Surgeon volume was divided into 3 quantiles: low (MNC = 4), medium (MNC = 10), and high (MNC = 26). Center volume was also divided into low (MNC = 14), medium (MNC = 32), and high (MNC = 64). After adjusting for potential confounders, and when compared with high-volume centers, low and medium center volumes were not associated with any increased odds of in-hospital stroke and death, stroke, death, or stroke with transient ischemic attack (TIA). Compared with high-volume surgeons, low surgeons’ volume was associated with a higher odd of stroke (odds ratio 1.5, 95% CI 1.1 to 2.04, p = 0.008), and stroke and TIA (OR 1.5, 95% CI 1.2 to 1.9, p = 0.002). However, medium surgeon volume was not associated with higher odds of stroke and death, stroke, and stroke with TIA. Neither low nor medium surgeon volume was associated with a difference in mortality compared with high surgeon volume.

CONCLUSIONS:

In this retrospective study, center volume was not associated with any differences in outcomes among patients undergoing TCAR. On the other hand, surgeons with low volume were associated with a higher risk of stroke, death, or MI and stroke or TIA when compared with high surgeon volume. There was no difference in outcomes between medium and high surgeon volume.
Delivery mode is a larger determinant of infant gut microbiome composition at 6 weeks than exposure to peripartum antibiotics
Authors: Leech Sophie M. , Borg Danielle J. , Rae Kym M. , Kumar Sailesh , Clifton Vicki L. , Dekker Nitert Marloes
Published: July 2024

Background. Previous research has shown that delivery mode can shape infant gut microbiome composition. However, mothers delivering by caesarean section routinely receive prophylactic antibiotics prior to delivery, resulting in antibiotic exposure to the infant via the placenta. Previously, only a small number of studies have examined the effect of delivery mode versus antibiotic exposure on the infant gut microbiome with mixed findings.

Objective. We aimed to determine the effect of delivery mode compared to antibiotic use during labour and delivery on the infant and maternal gut microbiome at 6 weeks post-partum.

Methodology. Twenty-five mother–infant dyads were selected from the longitudinal Queensland Family Cohort Study. The selected dyads comprised nine vaginally delivered infants without antibiotics, seven vaginally delivered infants exposed to antibiotics and nine infants born by caesarean section with routine maternal prophylactic antibiotics. Shotgun-metagenomic sequencing of DNA from stool samples collected at 6 weeks post-partum from mother and infant was used to assess microbiome composition.

Results. Caesarean section infants exhibited decreases in Bacteroidetes (ANCOM-BC q<0.0001, MaAsLin 2 q=0.041), changes to several functional pathways and altered beta diversity (R
2=0.056, P=0.029), while minimal differences due to antibiotic exposure were detected. For mothers, caesarean delivery (P=0.0007) and antibiotic use (P=0.016) decreased the evenness of the gut microbiome at 6 weeks post-partum without changing beta diversity. Several taxa in the maternal microbiome were altered in association with antibiotic use, with few differentially abundant taxa associated with delivery mode.

Conclusion. For infants, delivery mode appears to have a larger effect on gut microbiome composition at 6 weeks post-partum than intrapartum antibiotic exposure. For mothers, both delivery mode and intrapartum antibiotic use have a small effect on gut microbiome composition at 6 weeks post-partum.
Spectral-switching analysis reveals real-time neuronal network representations of concurrent spontaneous naturalistic behaviors in human brain
Authors: Zhu Hongkun , Michalak Andrew J. , Merricks Edward M. , Agopyan-Miu Alexander H. C. W. , Jacobs Joshua , Hamberger Marla J. , Sheth Sameer A. , McKhann Guy M. , Feldstein Neil , Schevon Catherine A. , Hillman Elizabeth M. C.
Published: July 2024

Despite abundant evidence of functional networks in the human brain, their neuronal underpinnings, and relationships to real-time behavior have been challenging to resolve. Analyzing brain-wide intracranial-EEG recordings with video monitoring, acquired in awake subjects during clinical epilepsy evaluation, we discovered the tendency of each brain region to switch back and forth between 2 distinct power spectral densities (PSDs 2-55Hz). We further recognized that this ‘spectral switching’ occurs synchronously between distant sites, even between regions with differing baseline PSDs, revealing long-range functional networks that would be obscured in analysis of individual frequency bands. Moreover, the real-time PSD-switching dynamics of specific networks exhibited striking alignment with activities such as conversation and hand movements, revealing a multi-threaded functional network representation of concurrent naturalistic behaviors. Network structures and their relationships to behaviors were stable across days, but were altered during N3 sleep. Our results provide a new framework for understanding real-time, brain-wide neural-network dynamics.
Translating human drug use patterns into rat models: exploring spontaneous interindividual differences via refined drug self-administration procedures
Authors: D’Ottavio Ginevra , Pezza Sara , Modoni Jacopo , Reverte Ingrid , Marchetti Claudia , Zenoni Soami F. , Termine Andrea , Fabrizio Carlo , Maftei Daniela , Lattanzi Roberta , Esposito Giuseppe , Ragozzino Davide , Merlo Emiliano , Milella Michele S. , Ciccocioppo Roberto , Fumagalli Fabio , Venniro Marco , Badiani Aldo , Boix Fernando , Caprioli Daniele
Published: July 2024

Heroin and cocaine users tailor their dosage and frequency of use, as well as their method of administration, to maximize the drugs’ pleasurable effects and prevent withdrawal symptoms. On the other hand, many preclinical self-administration and choice experiments employ fixed unit doses and mandatory timeouts after doses (known as discrete dimension procedures). These restrictions fail to consider the distinct pharmacokinetic properties of heroin and cocaine, leading to uniform and comparable behaviors (including drug-taking patterns). This uniformity contrasts sharply with the significantly different ways humans use heroin and cocaine, which are characterized by highly individualized drug use behaviors. Here, we introduce a no-timeout procedure that overcomes this limitation (continuous dimension procedure).

We analyzed the heroin and cocaine taking- and seeking-patterns and estimated drug-brain levels in the presence or absence of timeout between drug injections. We further assessed how absence of timeout and the availability of drug or social peer (access time to the two rewards) affect drug preference. Removing the timeout had a profound effect on pattern of heroin taking and seeking, promoting the emergence of burst-like drug intake and social withdrawal as revealed by a discrete choice procedure. On the other hand, timeout removal had a lesser impact on cocaine taking and seeking and did not impact social preference. By removing timeout during self-administration and increasing the access time during choice resulted in a self-administration procedure that more closely mimic human heroin intake, offering a platform to identify novel medications.
Parallel Sampling of Protein-Ligand Dynamics
Authors: Masters Matthew R. , Mahmoud Amr H. , Lill Markus A.
Published: July 2024

Abstract

Molecular dynamics (MD) simulations of protein-ligand complexes are essential for computer-aided drug design. In particular they enable the calculation of free energies and thus binding affinities. However, these simulations require significant computational resources and can take days to weeks to achieve relatively short timescales compared to biologically relevant timescales. To address this issue, we introduce a method for non-sequential generation of MD samples using a generative deep neural network trained on a large corpus of protein-ligand complex simulations. The method generates accurate protein-ligand complexes with full protein and ligand flexibility and is able to recapitulate the conformation space sampled by MD simulations with high coverage. This development is a step forward towards one-shot molecular sampling that can be utilized in the calculation of protein-ligand free energies.3
Annexin A2 and lamin B join membrane recycling compartments for the assembly of biomolecular condensates operating in mitotic partitioning
Authors: Grindheim Ann Kari , Dale Hege A. , Novak Josef , Patil Sudarshan S. , Vedeler Anni , Saraste Jaakko
Published: July 2024

Localization of the actin-, lipid- and mRNA-binding protein Annexin A2 (AnxA2) in dividing cells revealed its presence in large spherical structures which are confined to the cell periphery and frequently co-align with astral microtubules. These structures emerge at prometaphase and disappear at telophase, coinciding with the mitotic breakdown and reformation of the nuclear envelope, respectively. Their size increases towards anaphase, while their number decreases, indicating that they are capable of fusion. Treatment of cells with propylene glycol caused rapid and reversible disassembly of the structures, providing additional evidence that they correspond to biomolecular condensates. Interestingly, the condensates contain compartments operating in biosynthetic or endocytic membrane recycling, defined by Rab1, Rab11 or endocytosed transferrin, but are devoid of other membrane organelles, implying that they constitute a mitotic reservoir for selected endomembranes. They also contain lamin B, which connects with the pericentrosomal membrane recycling compartments at prometaphase, when the nuclear lamina breaks down in parallel with centrosome separation. These results suggest that the peripheral condensates correspond to the enigmatic membranous spindle matrix implicated in spindle organization and organelle inheritance. The separating daughter cells at late anaphase contain equal numbers of the condensates, in accordance with their role in mitotic partitioning of endomembranes and other cytoplasmic components.
Proteins Derived From MRL/MpJ Tendon Provisional Extracellular Matrix and Secretome Promote Pro-Regenerative Tenocyte Behavior
Authors: Marvin Jason C. , Liu Ethan J. , Chen Hsin Huei , Shiovitz David A. , Andarawis-Puri Nelly
Published: July 2024

Tendinopathies are prevalent musculoskeletal conditions that have no effective therapies to attenuate scar formation. In contrast to other adult mammals, the tendons of Murphy Roths Large (MRL/MpJ) mice possess a superior healing capacity following acute and overuse injuries. Here, we hypothesized that the application of biological cues derived from the local MRL/MpJ tendon environment would direct otherwise scar-mediated tenocytes towards a pro-regenerative MRL/MpJ-like phenotype. We identified soluble factors enriched in the secretome of MRL/MpJ tenocytes using bioreactor systems and quantitative proteomics. We then demonstrated that the combined administration of structural and soluble constituents isolated from decellularized MRL/MpJ tendon provisional ECM (dPECM) and the secretome stimulate scar-mediated rodent tenocytes towards enhanced mechanosensitivity, proliferation, intercellular communication, and ECM deposition associated with MRL/MpJ cell behavior. Our findings highlight key biological mechanisms that drive MRL/MpJ tenocyte activity and their interspecies utility to be harnessed for therapeutic strategies that promote pro-regenerative healing outcomes.

Teaser

Proteins enriched in a super-healer mouse strain elicit interspecies utility in promoting pro-regenerative tenocyte behavior.
Deep learning-driven neuromorphogenesis screenings identify repurposable drugs for mitochondrial disease
Authors: Menacho Carmen , Okawa Satoshi , Álvarez-Merz Iris , Wittich Annika , Muñoz-Oreja Mikel , Lisowski Pawel , Pentimalli Tancredi Massimo , Rybak-Wolf Agnieszka , Inak Gizem , Zakin Shiri , Thevandavakkam Mathuravani , Petersilie Laura , Zaliani Andrea , Mlody Barbara , Seibt Annette , Donnelly Justin , Woleben Kasey , Fernandez-Checa Jose , Herebian Diran , Mayatepek Ertan , Rajewsky Nikolaus , Spinazzola Antonella , Schuelke Markus , Perlstein Ethan , Rossi Andrea , Distelmaier Felix , Holt Ian J. , Pless Ole , Rose Christine R. , Del Sol Antonio , Prigione Alessandro
Published: July 2024

Mitochondrial disease encompasses untreatable conditions affecting tissues with high energy demands. A severe manifestation of mitochondrial disease is Leigh syndrome (Leigh), which causes defects in basal ganglia and midbrain regions, psychomotor regression, lactic acidosis, and early death. We previously generated isogenic pairs of Leigh cerebral organoids and uncovered defects in neuromorphogenesis. Here, we leveraged on this disease feature to devise drug discovery pipelines. We developed a deep learning algorithm tailored for cell type-specific drug repurposing to identify drugs capable of promoting neuronal commitment. In parallel, we performed a survival drug screen in yeast and validated the repurposable hits on branching capacity in Leigh neurons. The two approaches independently highlighted azole compounds, Talarozole and Sertaconazole, both of which lowered lactate release and improved neurogenesis and neurite organization in Leigh midbrain organoids. Hence, targeting neuromorphogenesis has led to identify potential new drugs for mitochondrial disease and could prove an effective strategy for further drug discovery.
Goal-directed action preparation in humans entails a mixture of corticospinal neural computations
Authors: Wadsley Corey George , Nguyen Thuan , Horton Chris , Greenhouse Ian
Published: July 2024

The seemingly effortless ability of humans to transition from thinking about actions to initiating them relies on sculpting corticospinal output from primary motor cortex. This study tested whether canonical additive and multiplicative neural computations, well-described in sensory systems, generalize to the corticospinal pathway during human action preparation. We used non-invasive brain stimulation to measure corticospinal input-output across varying action preparation contexts during instructed-delay finger response tasks. Goal-directed action preparation was marked by increased multiplicative gain of corticospinal projections to task-relevant muscles and additive suppression of corticospinal projections to non-selected and task-irrelevant muscles. Individuals who modulated corticospinal gain to a greater extent were faster to initiate prepared responses. Our findings provide physiological evidence of combined additive suppression and gain modulation in the human motor system. We propose these computations support action preparation by enhancing the contrast between selected motor representations and surrounding background activity to facilitate response selection and execution.