bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Levels of CXCL10 in Patients with Lupus Nephritis and its Relation with Disease Activity
Authors: El shirbiny Nourhan A , El Ganzoury Amal M , Abaza Nouran M , Azab Manar A
Published: July 2024

Objective

To evaluate the levels of CXCL10 in lupus nephritis (LN) patients and its relation with the activity of lupus nephritis.

Patients and Methods

Thirty four lupus patients were enrolled in our study, 17patients had lupus nephritis (LN) and 17 patients were without evidence of had lupus nephritis (LWN). Seventeen healthy subjects were also participated as a control group. Complete biochemical and serological parameters were measured and their correlation with serum levels of CXCL10 were assessed in the studied groups.

Results

The mean age of the LN patients was 31.94 ± 6.37,the mean age of LWN patient was 31.11± 6.42 and the mean age of the controls was 30.471± 4.705, Serum levels of CXCL10 were significantly elevated in LN patients group than LWN and control group with p-value <0.001,While serum CXCL10 in LWN was statistically increased than control group with p-value<0.001. Based on the receiver operator characteristic (ROC) curve analysis the efficacy of Serum CXCL10 levels in LN in a sample of Egyptian SLE patient This biomarker may be useful due to its high accuracy, with a sensitivity 94.12% and specificity of 76.47% as a biomarker of nephritis in SLE. There were statistically significant positive correlations between CXCL10 and 24 urinary protein (p-value = 0.031) (r = 0.524), creatinine (p-value = 0.003) (r = 0.682), renal activity (RSLEDAI) (p-value = 0.013) (r = 0.590) and Activity index (p-value = 0.003) (r = 0.669), whereas there was negative correlations between them and C3 (p-value = 0.021) (r=-0.554).

Conclusion

Being higher in patients with LN, CXCL10 might play a role in the pathogenesis of the disease. In addition to its excellent diagnostic performance for discriminating patients with lupus nephritis from other SLE patients, it might be helpful to predict the onset and progression of lupus nephritis in SLE patients and to detect renal flares.
Neuromuscular Phrenic Nerve Ultrasound versus Nerve Conduction Study of Phrenic Nerve in Amyotrophic Lateral Sclerosis
Authors: El Helow Mohamed Ragaai , Ahmed Sahar Fathi , El Bably Mona Mohamed , ElHadba Dina Maamoun
Published: July 2024

Background

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that is, characterized by progressive loss of the upper (UMNs) and lower motor neurons (LMNs) at the spinal or bulbar level. In the most advanced stages, ALS patients will develop symptoms of dyspnea due to weakness of respiratory muscles and subsequently death in ALS.

Objective

To compare between neuromuscular ultrasound and nerve conduction study of phrenic nerve in the assessment of pulmonary function in Amyotrophic lateral sclerosis patients.

Patients and Methods

This was a case control study performed in Ain Shams University Hospitals in the period from 2/2022 to 8/2022. The study included 15 patients diagnosed with Amyotrophic lateral sclerosis according to El Escorial revised criteria and 15 healthy people served as controls. Patients were randomized by a simple computer generated method into two groups: A study group (n = 15) and a control group (n = 15).

Results

This study showed that PNCS is more sensitive than CSA in the assessment of respiratory affection in ALS. PNCS is simple and easy to do and doesn’t need a highly equipped device. Also PN amplitude has a normal value and many studies were done about it. To our knowledge no research studies this correlation between PN CSA and PN amplitude in the assessment of respiratory affection among ALS patients.

Conclusion

Electrodiagnosis and Neuromuscular ultrasound have a valuable role in the diagnosis and monitoring ALS patients. This study showed that PNCS is more sensitive than PN CSA by NMUS in the assessment of respiratory affection in ALS. PNCS is simple and easy to do and doesn’t need a highly equipped device. Also there were well established reference values as many researches studied electrophysiology of phrenic nerve.
Biparametric versus Multiparametric MRI in Cancer Prostate Detection
Authors: Mahmoud Ali Ayah Tarek , Sheha Aliaa Sayed , Ahmed Tolba Mohammed Kotb , Mohammed Zedan Nehal Sayed
Published: July 2024

Background

Prostate cancer is the most frequently diagnosed cancer among men in over one-half of the countries of the world. Multi-parametric MRI is currently recognized as the best imaging method for assessment of cancer prostate.

Aim of the Work

comparing the diagnostic accuracy of mpMRI and bpMRI, according to PI- RADS V2.1 using the histopathological results as the standard of reference.

Patients and Methods

41 suspected prostate cancer patients were enrolled in our study based on elevated PSA levels or abnormal digital rectal examination, underwent prostate MRI. Images were interpreted first without DCE-MRI sequence then DCE-MRI was included, and scores were recorded, once for bpMRI and once for mpMRI.

Results

ROC curve analysis revealed that the AUC for the bpMRI and mpMRI protocols in diagnosing cancer prostate were 0.953 and 0.950 respectively and the difference was not statistically significant (P-value=0.875). Sensitivity, specificity and accuracy were calculated to reveal that when using PI-RADS score of ≥ 3 as a cut-off, bpMRI and mpMRI had exactly the same sensitivity, specificity, accuracy, PPV and NPV (100, 62.5, 85% respectively). When increasing the cut-off point of PI-RADS score to ≥ 4, the sensitivity of bpMRI decreased from 100 to 80, specificity increased from 62.5 to 93.75 yet, accuracy remained the same (85.4%). Whereas the sensitivity of mpMRI remained 100, specificity increased from 62.5 to 68.75 and accuracy increased from 85.4% to 87.8%.

Conclusion

bpMRI without DCE-MRI sequence did not lead to significant differences in diagnostic accuracy when using PI-RADS V2.1.
The Value of Magnetic Resonance Enterography Activity Indices in Evaluation of Crohn’s Disease Clinical Activity
Authors: AbdelWahed Waly Dalia Emad , Ahmed Aya Yassin , Abdulhafiz Essam Mohamed
Published: July 2024

Background

Crohn’s disease is a chronic inflammatory segmental bowel disorder characterized by attacks of remission and exacerbation that can significantly affect the patients’ quality of life. Hence monitoring the disease activity is crucial to achieve longer symptom free intervals which may result either from active inflammation and its complications as deep ulceration, fistulae formation and abscesses or sequelae from longstanding inflammatory process as fibrotic scarring and strictures.

Aim of the Work

to compare the performance of the currently available scoring systems Maria, Clermont, CDMI and MEGS to the clinical disease activity index and endoscopic indices

Patients and Methods

the study was conducted at the Diagnostic Radiology Unit; Radiology Department, Ain Shams University Hospitals. Over a period of 9 months. Convenience sample of proven cases of Crohn’s disease based on clinical suspicion, biomarkers, endoscopy and histopathological specimens who were referred for MRE enterography at our institution.

Results

We studied the relevance of 18 different single MR parameters and 5 indices in conjunction with clinical and endoscopic based scores. Our aim was to identify if any of the MR parameters can be used solely or in combination with others (indices) as predictors of disease activity. In our study, we identified that the presence of ulcers reflected the clinical rather than the endoscopic severity. Other individual MR parameters couldn’t predict either the clinical or endoscopic severity. The MaRIA score showed significant correlation with the clinical but not endoscopic score. The simplified MaRIA score reflected both the endoscopic and clinical severity scores regarding their absolute values and severity grade. Neither Diffusion- MaRIA/Clermont nor the CDMI scores could predict the degree of clinical and endoscopic disease severity. MEGS score was the most reliable score in determining the endoscopic activity despite being a consuming score with relative subjectivity in comparison to the forementioned scores.

Conclusion

MR indices provide an adjunct tool for evaluation of disease activity and identifying the severe disease evidenced by MaRIA, simplified MaRIA and MEGS scores. However, the use of a single MR parameter doesn’t provide a true reflection of the ongoing disease process, even the presence of ulcers and haustral loss may be associated with chronic disease.
Role of Ultrasound Imaging in Detection and Diagnosis of Different Types of Inflammatory Breast Diseases
Authors: Amin Khedr Heba Salah Tawfik , Amin Sherine Kadry , Louka Amir Louis
Published: July 2024

Background

Mastitis refers to inflammation of the breast parenchyma, often presenting with pain, heat and redness that may be a debilitating illness with prolonged morbidity. It may also present with a wide array of other nonspecific symptoms, which may lead to delayed diagnosis and inappropriate treatment.

Aim of the Work

The study aims to discuss different types of inflammatory breast diseases encountered by ultrasound and to distinguish their diverse radiological findings aiding in the early diagnosis to establish good prognosis.

Patients and Methods

This was a cross-sectional study which was carried out at Ain Shams University Hospitals; the study was conducted on 75 women with inflammatory breast diseases referred to the Radiology Department and Surgical outpatient ‘s clinics.

Results

Follow up by u/s and histopathology of the studied group revealed that 72(96.0%) were resolved and 3(4.0%) were IDC by histopathology. Final results regarding our statistical findings for our cases in differentiation between inflammatory lesions of the breast with sensitivity about 85.98 and Specificity about 85.46, the AUC was 0.898.

Conclusion

Ultrasound plays a fundamental role in the diagnostic work up of mastitis patients. An ideal ultrasound should ensure an accurate diagnosis, guide for interventional procedures whenever necessary and should be used to monitor adequate management by short term follow up studies along the course of therapy.
MRI Imaging Appearance in Mullerian Duct Anomalies
Authors: Shebreya Naglaa Hussein , Elsaed Elsaed Yasmin Tharwat , Ragheb Samar Ramzy
Published: July 2024

Background

Müllerian duct anomalies include a complex spectrum of anatomical anomalies that arise from deviations during the normal development of the Müllerian ducts. In paediatrics, such defects cannot present with any clinical symptoms before puberty, yet, they can also have obstructive symptoms or a mass effect due to presence of a non communicating rudimentary horn or transverse vaginal septum. At the beginning of puberty, girls with these anomalies might have primary amenorrhea, pelvic pain or endometriosis. Müllerian duct anomalies have also associated with a variety of other congenital abnormalities.

Aim of the Work

To review MRI features of Mullerian Duct Anomalies and classify them according to ASRM and ESHRE-ESGE classifications.

Patients and Methods

The study was a case series study that included 37 patients who underwent pelvic MRI at Radiology Department “Ain Shams University hospitals” in Cairo, Egypt.

Results

In our study, Hypoplastic, Agenesis and Didelphysis found to have the same ratio of (21.6%), while Bicornuate uterus was (13.5%), septate (8.1%), unicornuate and transverse vaginal septum all were of (5.4%) incidence and the least common was arcuate uterus with (2.7%) incidence.

Conclusion

MRI is a highly helpful technique for evaluating female genital abnormalities and is able to consistently provide the essential imaging characteristics for the accurate identification of Mullerian malformations. Additionally, incidental pelvic disease and any related renal abnormalities may be thoroughly evaluated by MRI in a single scan, removing the need for additional diagnostic procedures.
Chest CT Features of Coronavirus Disease-19 (COVID-19) Pneumonia: Which Findings on Initial CT can Predict an Adverse Short-term Outcome?
Authors: Sharara Sherine Ibrahim , Naguib Alaasar Maha Mahmoud , Mohamed Abeer Maher Ali
Published: July 2024

Background

COVID-19 is a highly contagious viral disease that caused daunting challenges to the health care system; early diagnosis plays a pivotal role in management and prognosis of the disease.

Aim of the Work

To study the spectrum of chest CT features in coronavirus disease-19 (COVID- 19) pneumonia and to identify the initial CT findings that may have the potential to predict a poor short-term outcome.

Patients and Methods

This was a retrospective study that included 60 patients (30 clinically improved and 30 clinically deteriorated patients) with RT-PCR confirmed COVID-19 infection who referred to the Radiodiagnosis Department at Ain Shams University Hospitals for chest HRCT examination. An acceptance from the ethical committee of the Radiology Department and the ethical committee of Faculty of Medicine - Ain Shams University was obtained to use the data stored on PACs system with the patient’s consent waived being a retrospective study.

Results

Shortness of breath, fatigue and presence of other comorbidities were more common in unstable group, seen in 93%, 86% and 66% respectively. CT severity score was higher in unstable group ranging from 12 to 26 together with anteroposterior distribution, central and peripheral distribution, crazy paving and consolidation with air bronchogram.

Conclusion

Comparison between clinically stable and unstable COVID-19 patients regarding clinical data at admission and initial CT chest findings revealed that higher percentage of total lung affection, central and peripheral involvement, anteroposterior distribution, crazy paving, consolidation with air bronchogram and vessel enlargement were the harbingers of poor prognosis especially in patients of old age, having other comorbidities and presented with shortness of breath.
Flexible Ureteroscopy versus Retroperitoneal Laparoscopic Ureterolithotomy in the Management of upper Ureteric Stones Measuring from One to Two Centimeters: Randomized Prospective Study
Authors: Abou-Elfarag Badran Medhat Adel , El Shorbagy Amr Fekry , Tawfick Ahmed
Published: July 2024

Objective

This prospective study aims to compare the clinical efficacy and safety of flexible ureteroscopy versus laparoscopic ureterolithotomy in the management of upper ureteric stones measuring from one to two centimeters.

Methods

his randomized-prospective study was conducted on 64 patients admitted from Urology unit, Ain Shams University in the period from October 2020 till September 2022; only 56 patients were analyzed statistically and 8 patients were excluded due to shortage in post- operative data and follow up. Patients were divided into two groups Group A consists of 31 patients and Group B consists of 25 patients with matched age, gender and body mass index (BMI).

Results

In our study, The VAS score at 6 hours post-operative and day 1 post-operative was found to be 5.32 and 2.71 in FURS group and was found to be 7.28 and 3.28 in RPLU group respectively showing significant difference with (p- value <0.001 and 0.016 respectively) between the two groups with more satisfaction in FURS group mostly due to the absence of trocars incisions. The complications were classified according to modified Clavien classification system. No major complications such as septic shock or death were reported in either treatment groups. As regards the recovery to work in postoperative and follow up periods in the present study, there was a significant difference between both groups with (P-value <0.001), as we found that it takes about 4.56 ± 0.82 days in RPLU group and 3.06 ± 1.91 days in FURS group to return daily routine activities. As regards the stone free rate in follow up periods in the present study, there was a significant difference between both groups with (P-value 0,02), as we found that it was 100% and 80,6% in RPLU and FURS group respectively. Our success rate in RPLU group was found to be 100% in comparison to Irfan Nazir Mir et al which was 93.4% (28/30) with two patients (2/30) converted to open ureterolithotomy, either due to technical snag or due to difficulty in localizing the ureter laparoscopically.

Conclusion

Both F-URS and RTLU were safe and effective surgical procedures for treatment of large proximal ureteral stones. However, RTLU had a higher stone-free rate with comparable operating time and complication rate as compared to F-URS. Also as regards to postoperative pain, shorter hospital stay and faster return to daily activities, both have almost similar results.
Percutaneous Pharmacological Thrombolysis as an Effective Primary Mode of Management of Thrombosed Prosthetic Arterio-Venous Grafts
Authors: Hamada Nader Mohamed , Abdulrahman Salem Abdulrahman Mohamed Ahmed , Mohamed Elawady Karim Shalaby , AboElNeel Hamdy AbdelAzeem
Published: July 2024

Background

Thrombosis of prosthetic arterio-venous graft (PAVG) is the most common cause of failure of using this access for haemodialysis (HD) in end stage kidney disease (ESKD) patients. Many different open surgical and vascular techniques were described to restore the function of thrombosed PAVG.

Objectives

We wanted to assess the feasibility and patency rates following the continuous thrombolysis infusion using tissue Plasminogen Activator (tPA) followed by angiogram and angioplasty of stenotic segment(s) in thrombosed PAVG.

Methods

We performed retrospective analysis of prospectively collected data from patients who had a thrombosed AVG from January 2020 to January 2022. Thrombolysis took place maximum 7 days after thrombosis was diagnosed. We have excluded patients who were referred to us more than a week after thrombosis occurred and patients with relative or absolute contraindication for thrombolysis and/or anticoagulation.

Results

During the two years of the study, there were 58 patients referred to our centre with thrombosed PAVG. We have excluded 28 patients who didn’t fulfill inclusion criteria. We have performed PAVG continuous thrombolysis infusion using tPA till we have achieved reopening of the thrombosed PAVG followed by angiography and angioplasty. All patients had venous anastomosis stenosis while 17 patients had stenosis in the graft and only 5 had a stenosis at the arterial anastomosis. During the period of follow up primary patency was achieved in 80% of our patients while our primary assisted patency was 86.67%

Conclusions

Endovascular tPA thrombolysis for early thrombosis of prosthetic AVAs is feasible, safe, and is associated with an excellent technical success and very good 12 months patency rate.
Host Genetic Resistance in Brassica napus: A Valuable Tool for the Integrated Management of the Fungal Pathogen Leptosphaeria maculans
Authors: Sprague Susan J. , Van de Wouw Angela P. , Marcroft Stephen J. , Geffersa Abebayehu G. , Idnurm Alexander , Barrett Luke G.
Published: July 2024

Management of plant disease in agro-ecosystems ideally relies on a combination of host genetic resistance, chemical control, and cultural practices. Growers increasingly rely on chemical and genetic options, but their relative benefits in disease control, yield, and economic outcomes are rarely quantified. We explore this relationship for blackleg crown canker disease (caused by Leptosphaeria maculans), a major biotic constraint limiting canola production globally. Data from 20 field trials conducted from 2013 to 2015 in canola-growing regions of Australia were used to assess the effects of host resistance and fungicide treatment on blackleg severity, grain yield, and gross margin. In the absence of fungicide, blackleg disease was 88% lower in the most resistant compared with the most susceptible blackleg resistance category. In the most susceptible resistance category, the most effective fungicide treatment significantly reduced blackleg severity (from 50 to 6%) and increased grain yield (478 kg/ha, 41%) and gross margin (AU$120/ha, 17%). However, the mean benefits of fungicide tended to decrease with increasing levels of genetic resistance, to the point that yield, disease, and gross margin benefits were close to zero in the most resistant cultivars. Overall, these findings suggest that fungicides can reduce blackleg severity, but the benefits of application strongly depend on associated levels of genetic resistance. Canola cultivars with higher genetic resistance reliably reduced blackleg disease and maintained grain yield without the associated cost of fungicide application. The intensification of canola production to meet increasing global demand will require strategies to sustainably manage and protect finite genetic resistance resources to control blackleg disease.
Social defeat stress impairs systemic iron metabolism by activating the hepcidin–ferroportin axis
Authors: Kasahara Emiko , Nakamura Ayumi , Morimoto Kenki , Ito Shiho , Hori Mika , Sekiyama Atsuo
Published: July 2024

Chronic psychological stress has been reported to decrease circulating iron concentrations and impair hematopoiesis. However, the underlying mechanisms remain unclear. This study aimed to investigate the effects of psychological stress on biological iron metabolism by using the social defeat stress (SDS) model, a widely used model of depression. Compared with control mice, mice subjected to SDS (SDS mice) had lower social interaction (SI) behavior. The SDS mice also showed impaired hematopoiesis, as evidenced by reduced circulating red blood cell counts, elevated reticulocyte counts, and decreased plasma iron levels. In the SDS mice, the iron contents in the bone marrow decreased, whereas those in the spleen increased, suggesting dysregulation in systemic iron metabolism. The concentrations of plasma hepcidin, an important regulator of systemic iron homeostasis, increased in the SDS mice. Meanwhile, the concentrations of ferroportin, an iron transport protein negatively regulated by hepcidin, were lower in the spleen and duodenum of the SDS mice than in those of the control mice. Treatment with dalteparin, a hepcidin inhibitor, prevented the decrease in plasma iron levels in the SDS mice. The gene expression and enzyme activity of furin, which converts the precursor hepcidin to active hepcidin, were high and positively correlated with plasma hepcidin concentration. Thus, furin activation might be responsible for the increased plasma hepcidin concentration. This study is the first to show that psychological stress disrupts systemic iron homeostasis by activating the hepcidin–ferroportin axis. Consideration of psychological stressors might be beneficial in the treatment of diseases with iron‐refractory anemia.
The correlation between TRIM28 expression and immune checkpoints in CRPC
Authors: Xue Dun , Zuo Qian , Chang Jie , Wu Xinghui
Published: July 2024

This study delves into the unexplored realm of castration‐resistant prostate cancer (CRPC) by investigating the role of TRIM28 and its intricate molecular mechanisms using high‐throughput single‐cell transcriptome sequencing and advanced bioinformatics analysis. Our comprehensive examination unveiled dynamic TRIM28 expression changes, particularly in immune cells such as macrophages and CD8+ T cells within CRPC. Correlation analyses with TCGA data highlighted the connection between TRIM28 and immune checkpoint expression and emphasized its pivotal influence on the quantity and functionality of immune cells. Using TRIM28 knockout mouse models, we identified differentially expressed genes and enriched pathways, unraveling the potential regulatory involvement of TRIM28 in the cGAS‐STING pathway. In vitro, experiments further illuminated that TRIM28 knockout in prostate cancer cells induced a notable anti‐tumor immune effect by inhibiting M2 macrophage polarization and enhancing CD8+ T cell activity. This impactful discovery was validated in an in situ transplant tumor model, where TRIM28 knockout exhibited a deceleration in tumor growth, reduced proportions of M2 macrophages, and enhanced infiltration of CD8+ T cells. In summary, this study elucidates the hitherto unknown anti‐tumor immune role of TRIM28 in CRPC and unravels its potential regulatory mechanism via the cGAS‐STING signaling pathway. These findings provide novel insights into the immune landscape of CRPC, offering promising directions for developing innovative therapeutic strategies.
Exploration of the miR‐187‐3p/CNR2 pathway in modulating osteoblast differentiation and treating postmenopausal osteoporosis through mechanical stress
Authors: Zhang Lei , Zeng Canjun , Huang Juanyu , Yan Haohang , Jiang Yutao , Li Runguang
Published: July 2024

This study aimed to explore how mechanical stress affects osteogenic differentiation via the miR‐187‐3p/CNR2 pathway. To conduct this study, 24 female C57BL/6 mice, aged 8 weeks, were used and divided into four groups. The Sham and OVX groups did not undergo treadmill exercise, while the Sham + EX and OVX + EX groups received a 8‐week treadmill exercise. Post‐training, bone marrow and fresh femur samples were collected for further analysis. Molecular biology analysis, histomorphology analysis, and micro‐CT analysis were conducted on these samples. Moreover, primary osteoblasts were cultured under osteogenic conditions and divided into GM group and CTS group. The cells in the CTS group underwent a sinusoidal stretching regimen for either 3 or 7 days. The expression of early osteoblast markers (Runx2, OPN, and ALP) was measured to assess differentiation. The study findings revealed that mechanical stress has a regulatory impact on osteoblast differentiation. The expression of miR‐187‐3p was observed to decrease, facilitating osteogenic differentiation, while the expression of CNR2 increased significantly. These observations suggest that mechanical stress, miR‐187‐3p, and CNR2 play crucial roles in regulating osteogenic differentiation. Both in vivo and in vitro experiments have confirmed that mechanical stress downregulates miR‐187‐3p and upregulates CNR2, which leads to the restoration of distal femoral bone mass and enhancement of osteoblast differentiation. Therefore, mechanical stress promotes osteoblasts, resulting in improved osteoporosis through the miR‐187‐3p/CNR2 signaling pathway. These findings have broad prospect and provide molecular biology guidance for the basic research and clinical application of exercise in the prevention and treatment of PMOP.
Insights into the role of glycerophospholipids on the iron export function of SLC40A1 and the molecular mechanisms of ferroportin disease
Authors: Debbiche Rim , Elbahnsi Ahmad , Uguen Kévin , Ka Chandran , Callebaut Isabelle , Le Gac Gérald
Published: July 2024

SLC40A1 is the sole iron export protein reported in mammals. In humans, its dysfunction is responsible for ferroportin disease, an inborn error of iron metabolism transmitted as an autosomal dominant trait and observed in different ethnic groups. As a member of the major facilitator superfamily, SLC40A1 requires a series of conformational changes to enable iron translocation across the plasma membrane. The influence of lipids on protein stability and its conformational changes has been little investigated to date. Here, we combine molecular dynamics simulations of SLC40A1 embedded in membrane bilayers with experimental alanine scanning mutagenesis to analyze the specific role of glycerophospholipids. We identify four basic residues (Lys90, Arg365, Lys366, and Arg371) that are located at the membrane‐cytosol interface and consistently interact with 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (POPC) and 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphoethanolamine (POPE) molecules. These residues surround a network of salt bridges and hydrogens bonds that play a critical role in stabilizing SLC40A1 in its basal outward‐facing conformation. More deeply embedded in the plasma membrane, we identify Arg179 as a charged amino acid residue also tightly interacting with lipid polar heads. This results in a local deformation of the lipid bilayer. Interestingly, Arg179 is adjacent to Arg178, which forms a functionally important salt‐bridge with Asp473 and is a recurrently associated with ferroportin disease when mutated to glutamine. We demonstrate that the two p.Arg178Gln and p.Arg179Thr missense variants have similar functional behaviors. These observations provide insights into the role of phospholipids in the formation/disruption of the SLC40A1 inner gate, and give a better understanding of the diversity of molecular mechanisms of ferroportin disease.
Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II hepatocellular carcinoma undergoing surgery? An observational cohort study
Authors: Lee Chao-Wei , Tsai Hsin-I , Hsu Hsiao-Mei , Yu Ming-Chin , Lee Wei-Chen , Wang Chih-Chi , Hsieh Yi-Chung , Lin Cheng-Yu , Cheng Mei-Ling , Lo Chi-Jen , Wang Ching-Ting , Lin Yu-Ching
Published: July 2024

Introduction:

The influence of deranged body composition on stage I/II hepatocellular carcinoma (HCC) after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed.

Methods:

From 2012 to 2021, stage I and II HCC patients who underwent liver resection at our institute were retrospectively reviewed. Their preoperative body composition including skeletal muscle mass and body fat volume was measured by computed tomography (CT). The recurrence outcome was recorded and analyzed. The preoperative serum was collected and subjected to metabolomic analysis.

Results:

A total of 450 stage I and II HCC patients were included in the current study. Among them, 76% were male and around 60% had HBV infection. After stratified by normal cut-off values obtained from a healthy cohort, 6.4% of stage I/II HCC patients were found to have a low psoas muscle index (PMI), 17.8% a high subcutaneous adipose tissue (SAT) index, and 27.8% a high visceral adipose tissue (VAT) index. Cox regression multivariate analysis further demonstrated that low PMI and high SAT index were independent prognostic factors for time-to-recurrence (TTR) after surgery. Metabolomic analysis discovered that free fatty acid β-oxidation was enhanced in patients with low PMI or high SAT index.

Conclusion:

The current study demonstrated that reduced psoas muscle mass may impair while elevated SAT may prolong the TTR of stage I/II HCC patients undergoing liver resections. VAT, on the other hand, was not associated with recurrence outcomes after surgery. Further studies are warranted to validate our findings.
Clinical efficacy of different therapeutic strategies in patients with spontaneous rupture of the esophagus: a multicenter retrospective cohort study
Authors: Luan Siyuan , Xiao Xin , Zeng Xiaoxi , Ren Jie , Liu Wen , Luo Jiwen , Mei Xinyu , Zhou Xinpeng , Li Rulin , Deng Yufeng , Fu Maoyong , Shi Guidong , Du Shijian , Wu Yunhua , Li Chong , Wang Yuncang , Li Gang , Yang Changjie , Zhou Jianfeng , Mao Chengyi , Hu Weipeng , Chen Longqi , Yang Yushang , Yuan Yong
Published: July 2024

Background:

The therapeutic strategy for patients with spontaneous rupture of the esophagus includes surgical repair, endoscopic therapy, supportive care, and others. However, no evidence exists to direct clinical decision-making regarding the choice of operative and nonoperative management. This study aimed to determine the clinical efficacy of different therapeutic strategies in both general and stratified patients.

Methods:

This study retrospectively analyzed a consecutive cohort of 101 patients at nine tertiary referral hospital centers in China. Patients were divided into operative and nonoperative groups based on the initial treatment. Short-term outcomes, including 90-day mortality, length of hospital stay, and postoperative leakage, were compared. Subgroup analysis was performed based on treatment timing and Pittsburgh perforation severity score.

Results:

Of 101 patients, 60 (58.4%) underwent operative management. A significant difference in 90-day mortality between operative and nonoperative groups was observed (15.0 vs. 34.1%; P=0.031). Operative management tends to yield similar therapeutic benefits in timely [odds ratio (OR), 0.250; 95% confidence interval (CI), 0.05–1.14; P=0.073) and delayed (OR, 0.42; 95% CI, 0.12–1.47; P=0.175) treatment groups. Based on perforation severity score stratification, operative management significantly decreased the risk of 90-day mortality (OR, 0.211; 95% CI, 0.064–0.701; P=0.011) for patients in low-risk and moderate-risk groups but may be detrimental for patients in high-risk group (OR, 1.333; 95% CI, 0.233–7.626; P=0.746).

Conclusions:

Operative management might be superior to nonoperative management for low-risk and moderate-risk patients with spontaneous rupture of the esophagus. However, for patients at high risk, operative management might not provide additional benefits compared with nonoperative management. Further research involving larger sample sizes is required for accurate patient stratification and conclusive evidence-based guidelines.
Pulmonary rehabilitation in idiopathic pulmonary fibrosis
Authors: Dowman Leona M. , Holland Anne E.
Published: July 2024

Purpose of review

This review synthesizes the expanding evidence for pulmonary rehabilitation that has led to its recommended inclusion in the holistic care of people with idiopathic pulmonary fibrosis (IPF), as well as discussing strategies that may maximize and sustain benefits.

Recent findings

Pulmonary rehabilitation is an effective intervention leading to significant improvements in exercise tolerance, symptoms, and quality of life for people with IPF. Improvements in symptoms and quality of life can persist longer term, whereas functional capacity does not; therefore, strategies to preserve functional capacity are an important area of research. Referral early in the disease course is encouraged to promote longer lasting effects. Evidence that high-intensity interval training may optimize benefits of exercise training is emerging. Supplemental oxygen is frequently used to manage exercise-induced desaturation, although its use as an adjunct therapy requires more evidence.

Current evidence strongly supports the inclusion of pulmonary rehabilitation in the standard holistic care of IPF, with early participation encouraged. Further research is needed to establish the optimal exercise strategies, modalities and adjunct therapies that enhance outcomes of pulmonary rehabilitation and promote longer lasting effects.
Do Medicare Inpatient Rehabilitation Facility Patients’ Self-care and Mobility Outcomes Vary by Dual Eligibility Status, Race and Ethnicity, Rural Residence, Socioeconomic Status, and Living Alone?
Authors: Deutsch Anne , Palmer Lauren , McMullen Tara , Luke Jordi , Kwon Sophia , Ingber Melvin J.
Published: July 2024

Objective

The aim of the study is to examine whether inpatient rehabilitation facility patients’ risk-adjusted functional outcomes varied with the following five social drivers of health: Medicare-Medicaid dual eligibility status, race and ethnicity, rural residence, socioeconomic status, and living alone.

Design

This cohort study examined unadjusted and adjusted mobility and self-care change scores during inpatient rehabilitation facility stays for 428,710 Medicare patients with and without social drivers of health. Regression models isolated the mean marginal effect of each of the five social factors on mobility and self-care change scores after adjusting for covariates.

Results

Patients with full dual status had slightly lower risk-adjusted mobility and self-care improvement (−4.5% and −3.3%, respectively) compared with patients without dual status. Patients who identified as Black, Asian, and Native Hawaiian had self-care marginal effects that were slightly lower (−4.8%, −4.1%, and −3.7%, respectively) than patients who were White. Patients living in lower socioeconomic status neighborhoods and patients who lived alone had slightly higher mobility and self-care improvement scores. Risk-adjusted marginal differences in improvement scores for patients with and without these social factors were small and did not meet the meaningfully different criteria.

Conclusion(s)

Overall, inpatient rehabilitation facility patients’ risk-adjusted functional outcomes did not vary meaningfully by dual eligibility status, race or ethnicity, rural residence, socioeconomic status. or living alone.
Characterizing Sentinel Lymph Node Status in Breast Cancer Patients Using a Deep-Learning Model Compared With Radiologists' Analysis of Grayscale Ultrasound and Lymphosonography
Authors: Machado Priscilla , Tahmasebi Aylin , Fallon Samuel , Liu Ji-Bin , Dogan Basak E. , Needleman Laurence , Lazar Melissa , Willis Alliric I. , Brill Kristin , Nazarian Susanna , Berger Adam , Forsberg Flemming
Published: July 2024

The objective of the study was to use a deep learning model to differentiate between benign and malignant sentinel lymph nodes (SLNs) in patients with breast cancer compared to radiologists' assessments.

Seventy-nine women with breast cancer were enrolled and underwent lymphosonography and contrast-enhanced ultrasound (CEUS) examination after subcutaneous injection of ultrasound contrast agent around their tumor to identify SLNs. Google AutoML was used to develop image classification model. Grayscale and CEUS images acquired during the ultrasound examination were uploaded with a data distribution of 80% for training/20% for testing. The performance metric used was area under precision/recall curve (AuPRC). In addition, 3 radiologists assessed SLNs as normal or abnormal based on a clinical established classification. Two-hundred seventeen SLNs were divided in 2 for model development; model 1 included all SLNs and model 2 had an equal number of benign and malignant SLNs. Validation results model 1 AuPRC 0.84 (grayscale)/0.91 (CEUS) and model 2 AuPRC 0.91 (grayscale)/0.87 (CEUS). The comparison between artificial intelligence (AI) and readers' showed statistical significant differences between all models and ultrasound modes; model 1 grayscale AI versus readers, P = 0.047, and model 1 CEUS AI versus readers, P < 0.001. Model 2 r grayscale AI versus readers, P = 0.032, and model 2 CEUS AI versus readers, P = 0.041.

The interreader agreement overall result showed κ values of 0.20 for grayscale and 0.17 for CEUS.

In conclusion, AutoML showed improved diagnostic performance in balance volume datasets. Radiologist performance was not influenced by the dataset’s distribution.
Pathological insights derived from neuroimaging in amyotrophic lateral sclerosis: emerging clinical applications
Authors: Tu Sicong , Vucic Steve , Kiernan Matthew C.
Published: July 2024

Purpose of review

Neuroimaging has been instrumental in shaping current understanding of the pathoanatomical signature of amyotrophic lateral sclerosis (ALS) across clinically well defined patient cohorts. The potential utility of imaging as an objective disease marker, however, remains poorly defined.

Recent findings

Increasingly advanced quantitative and computational imaging studies have highlighted emerging clinical applications for neuroimaging as a complementary clinical modality for diagnosis, monitoring, and modelling disease propagation. Multimodal neuroimaging has demonstrated novel approaches for capturing primary motor disease. Extra-motor subcortical dysfunction is increasingly recognized as key modulators of disease propagation.

The neural signature of cortical and subcortical dysfunction in ALS has been well defined at the population level. Objective metrics of focal primary motor dysfunction are increasingly sensitive and translatable to the individual patient level. Integrity of extra-motor subcortical abnormalities are recognized to represent critical pathways of the ALS disease ‘connectome’, predicting pathological spread. Neuroimaging plays a pivotal role in capturing upper motor neuron pathology in ALS. Their potential clinical role as objective disease markers for disease classification, longitudinal monitoring, and prognosis in ALS have become increasingly well defined.
ICTV Virus Taxonomy Profile: Phasmaviridae 2024
Authors: Kuhn Jens H. , Hughes Holly R.
Published: July 2024

Phasmaviridae is a family for negative-sense RNA viruses with genomes of about 9.7–15.8 kb. These viruses are maintained in and/or transmitted by insects. Phasmavirids produce enveloped virions containing three single-stranded RNA segments that encode a nucleoprotein (N), a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Phasmaviridae, which is available at ictv.global/report/phasmaviridae.
Genomic and single-cell characterization of patient-derived tumor organoid models of head and neck squamous cell carcinoma
Authors: Um Jung Hyun , Zheng Yueyuan , Mao Qiong , Nam Chehyun , Zhao Hua , Koh Yoon Woo , Shin Su-Jin , Park Young Min , Lin De-Chen
Published: July 2024

Head and Neck Squamous Cell Carcinoma (HNSCC) remains a significant health burden due to tumor heterogeneity and treatment resistance, emphasizing the need for improved biological understanding and tailored therapies. This study enrolled 31 HNSCC patients for the establishment of patient-derived tumor organoids (PDOs), which faithfully maintained genomic features and histopathological traits of primary tumors. Long-term culture preserved key characteristics, affirming PDOs as robust representative models. PDOs demonstrated predictive capability for cisplatin treatment responses, correlatingex vivodrug sensitivity with patient outcomes. Bulk and single-cell RNA sequencing unveiled molecular subtypes and intratumor heterogeneity (ITH) in PDOs, paralleling patient tumors. Notably, a hybrid epithelial-mesenchymal transition (hEMT)-like ITH program is associated with cisplatin resistance and poor patient survival. Functional analyses identified amphiregulin (AREG) as a potential regulator of the hybrid epithelial/mesenchymal state. Moreover, AREG contributes to cisplatin resistance via EGFR pathway activation, corroborated by clinical samples. In summary, HNSCC PDOs serve as reliable and versatile models, offer predictive insights into ITH programs and treatment responses, and uncover potential therapeutic targets for personalized medicine.

One Sentence Summary

This study establishes patient-derived tumor organoids (PDOs) from 31 Head and Neck Squamous Cell Carcinoma (HNSCC) patients, faithfully recapitulating characteristics of primary tumors and accurately predicting clinical responses to cisplatin treatment. We reveal intertumoral heterogeneity within PDOs and a hybrid epithelial-mesenchymal transition (hEMT) program conferring cisplatin resistance, highlighting amphiregulin (AREG) as a regulator of cellular plasticity and potential therapeutic target for HNSCC treatment.
Network architecture of transcriptomic stress responses in zebrafish embryos
Authors: Beine Kaylee , Feugere Lauric , Turner Alexander P. , Valero Katharina C. Wollenberg
Published: July 2024

Protein-protein interaction (PPI) network topology can contribute to explain fundamental properties of genes, from expression levels to evolutionary constraints. Genes central to a network are more likely to be both conserved and highly expressed, whereas genes that are able to evolve in response to selective pressures but expressed at lower levels are located on the periphery of the network. The stress response is likewise thought to be conserved, however, experimental evidence for these patterns is limited. We examined whether the transcriptomic response to two environmental stressors (heat, UV, and their combination) is related to PPI architecture in zebrafish (Danio rerio)embryos. We show that stress response genes are situated more centrally in the PPI network. The transcriptomic response to heat was located in both central and peripheral positions, whereas UV response occupied central to intermediate positions. Across treatments, differentially expressed genes in different parts of the network affected identical phenotypes. Our results indicate that the zebrafish stress response has mostly conserved but also some stressor-specific aspects. These properties can aid in better understanding the organismal response to diverse and co-occurring stressors. Network position was further linked to the magnitude of fold changes of genes and types and number of linked phenotype components. Given the speed of contemporary changes in aquatic ecosystems, our approach can aid in identifying novel key regulators of the systemic response to specific stressors.
Devonian stromatoporoid historical collections in the Natural History Museum, London (UK): redescription, taxonomic revision and implications for stromatoporoid global paleobiogeography
Authors: Huang Jiayuan , Sendino Consuelo , Kershaw Stephen
Published: July 2024

Devonian stromatoporoid collections in the Natural History Museum, London (UK) have been deposited for over 100 years. The characteristics and systematic position of these specimens, however, have received little attention. In this study, a total of 307 Devonian stromatoporoid specimens comprising material documented by Nicholson (1886–1892) from the UK, Germany, United States, and Canada, plus specimens described by Ripper (1933, 1937a, b, c) from Australia, were re-examined. Overall, 50 species belonging to 29 genera were systematically redescribed based on recent progress, mainly includingActinostroma,Petridiostroma,Stictostroma,Pseudotrupetostroma,Parallelopora. Three-dimensional reconstructions of the type genus are illustrated following the earlier works of Stearn (1966) and Cockbain (1984). The reconstructed skeletons reveal stromatoporoid architectural patterns, crucial for enhancing understanding and revision of stromatoporoid identification. This study underscores the significance of three-dimensional reconstruction in taxonomic research on stromatoporoid. The NHMUK material is combined with data from publications and the Paleobiology Database (PBDB) to perform a network analysis of the global occurrence of Devonian stromatoporoids at the generic level; this reveals a close relationship of global stromatoporoid fauna during the Early Devonian, indicating a widespread distribution, despite this interval being regarded as a time of global stromatoporoid contraction. The Middle Devonian assemblage shows a much higher cosmopolitan occurrence in the context of the subsequent Eifelian-Givetian global stromatoporoid proliferation, consistent with the known pattern from other studies of Middle Devonian stromatoporoids. Overall, the NHMUK collections are a valuable resource to help understand the global occurrence of Devonian stromatoporoids.