bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian _ Reporting and Data System (O_RADS) Classification of Ovarian Lesions on Ultrasound Basis
Authors: Abd El-Ghaffar Azza , Wahby Tarek , Wardany Gweada Hanan Gweada
Published: July 2024

Background

Ovarian lesions present a special diagnostic challenge when imaging findings cannot be categorized into benign or malignant pathology. Ultrasonography (US), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) are currently used to evaluate ovarian tumors.

Aim of the Work

The aim of this work is to determine the efficacy of the classification of ovarian lesions on an ultrasound basis.

Patients and Methods

This was a prospective observational study conducted on 30 females with ovarian lesions at the Radiology Department of Ain Shams University Hospitals for 6 months from February to august 2022.

Results

The benign lesions of O-RADS 1, O-RADS 2, O-RADS 3, O-RADS 4, and O-RADS 5 represented 5.3%, 63.2%, 15.8%, 10.5% and 5.3% respectively. The malignant lesions of O-RADS 5, O- RADS 4 represented 81.8%, and 18.2%, respectively. There was a highly statistically significant difference between benign and malignant lesions in terms of the O-RADS score (P < 0.001). In order to assess the diagnostic performance of the O-RADS score to discriminate malignant from benign lesions, a ROC curve analysis was performed. O-RADS score (AUC of 0.959) showed a sensitivity of 100%, a specificity of 84.21%, PPV of 78.6%, and NPV of 100%, with the optimal cutoff value for predicting malignancy was >O-RADS 3.

Conclusion

The current study concluded the following: Ultrasonography is definitely an important non- invasive tool and is helpful in diagnosing most cases of ovarian lesions. O-RADS system has good sensitivity and moderate specificity for classifying ovarian lesions.
The Efficiency of Volumetry in Graft Weight Assessment in Living Donor Liver Transplant
Authors: Hassan Mohammed Sobhy , Abbas Sherif Nabil , Elbeheiry Mona Mohamed , Salama Shalaby Nourhan Ahmed
Published: July 2024

Background

Liver transplantation is the treatment of choice for end-stage hepatic diseases. The most important factor responsible for the success of the transplant is the size of the graft and the remnant liver volume in the donor. A small graft may not meet the metabolic demands of the recipient resulting in impaired liver functions such as hyperbilirubinemia, prolonged prothrombin time (PT), ascites and portal hypertension.

Patient and Methods

This comparative study was conducted on manual contrast enhanced hepatic CT scans of 40 potential living liver donors (29) male and (11) female Age range from (18 to 50 ) in Ain shams specialized hospital and some private centers during the period from May 2021 till July 2022. The potential donors were investigated using 16 channel multi-detector row CT scanner (Alexion; Toshiba medical systems). All potential donors underwent 1st step laboratory investigations to enter the 2nd step investigations for living donor liver transplantation operations. All potential donors were of average weight and physically fit for operation with no history of any medical diseases.

Results

We correlated the results of CT volumetry of right lobe graft weight with the intra-operative weight of liver graft in patients undergoing Living Donor Liver Transplantation(LDLT). CT Volumetry is an efficient and a reliable tool for assessing potential donors undergoing liver transplant, and this information is essential for donor selection and pre operative surgical planning as well as it ensure that the liver remnant volume is at least 30 % which guarantee the safety of the donor.

Conclusion

The size of the right lobe graft for LDLT can be precisely calculated from pre-operative CT Volumetry with confidence and accuracy up to 95%.
Safety and Efficacy of Directly Acting Antiviral Drugs in Treatment of Chronic HCV Egyptian Patients
Authors: Abdella Heba Mohamed , El Breedy Ashraf Mohammad , Al-Balakosy Amira Mahmoud , El Kassas Mohamed Mahmoud , Mohamed Hegazy Ghada Assem Mohamed
Published: July 2024

Background

The emergence of direct antiviral agents (DAAs), and the campaign done by the National Committee for Control of Viral Hepatitis (NCCVH) have reduced chronic hepatitis C (CHC) prevalence in Egypt.

Objectives

evaluate the efficacy and safety of used DAAs in affiliated centers.

Methods

an observational prospective and retrospective study including140 eligible patients from October 2017 till December 2019 and who were either starting treatment or during follow- up for 1 year after the end of therapy (EOT). Patients were divided according to the treatment regimen into Group I (SOF/DAC for 12 weeks), Group II (SOF/DAC/RBV for 12 weeks), Group III (SOF/SIM for 12 weeks), Group IV (SOF/DAC for 24 weeks) and Group V (SOF/DAC/RBV for 24 weeks).

Results

DAAs were effective in all groups. Adverse effects occurred in 54 patients (38.6%). The most common complications that occurred were ascites (n = 18) followed by jaundice (n = 17) and hepatocellular carcinoma (HCC) (n = 14). Almost all patients (97.1%) in group IV complained of adverse effects compared to other groups with a statistically significant difference (p < 0.001). Hematemesis occurred in one patient among the whole groups and this patient had been in group IV. There was also a significantly higher proportion of ascites (38.2%) in group IV compared to other groups (p < 0.01), however no significant differences between groups regarding HCC and renal impairment (RI) (p-value= 0.316 and 0.758 respectively) were found. 49 naïve patients suffered from side effects, 31 patients were in group IV, followed by group I (n = 7) then group II (n = 6). 5 experienced patients reported side effects. RI was the most reported side effect (12.5%) among interferon (IFN) experienced and SOF/DAC experienced patients and who were treated among group IV and group V. Hepatic encephalopathy was equally reported (12.5%) in IFN experienced and SOF/RBV experienced patients among group IV or group V. Ascites (6.3%) and jaundice (6.3%) also were reported among group IV. No experienced patient has complained of hematemesis or HCC.

Conclusion

SOF/RBV treatment for 24 weeks had many side effects and should be used with caution.
Clinical Utility of CTNNB1 (c.121A>G) Mutation in Circulating Tumor DNA in Egyptian Patients with Hepatocellular Carcinoma: A Case-Control Study
Authors: Abdallah Nourhan Mohamed , Abdelhakam Dina A , Salah Manar , Montasser Iman , Hamdy Perihan , Salem Ramy
Published: July 2024

Background

Hepatocellular carcinoma (HCC) is the most common malignancy of the liver and with 782,000 new cases annually and 600,000 deaths/year globally. In Egypt, HCC causes a significant public health problem with a rising incidence as it is strongly linked to viral hepatitis mainly HCV. CTNNB1 mutations is one of the most common genetic alterations in HCC. Our aim is to investigate the clinical utility of CTNNB1 (rs121913412) single nucleotide variation (SNV) in ctDNA in patients with early and late-stage HCC in comparison to chronic HCV patients and healthy controls.

Methods

All participants were subjected to history taking, clinical evaluation, laboratory investigations including liver profile, kidney function tests, alfa-fetoprotein. Additionally, complete blood counts and coagulation profile were done. Child and Model for End-Stage Liver Disease (MELD) scores were calculated, BCLC staging was done for each patient and radiological protocol for HCC (spiral triphasic CT or MRI). Genotyping of rs121913412 CTNNB1 (c.121A>G) on extracted DNA from blood samples was done using Real Time PCR System.

Results

Thirty patients with HCC on top of HCV were recruited including 14 early HCC and 16 with advanced HCC in addition to non-HCC group including 10 HCV-positive patients and 10 healthy controls. All participants have undergone laboratory investigations and radiological protocol for HCC cases. Genotyping of rs121913412 CTNNB1 (c.121A>G) in peripheral blood samples using RT-PCR for all cases was done. The genotype AA was detected in 27out of 30 (30%) of the cases while 3 HCC cases out of 30 (10 %) were positive for the CTNNB1 p.T41A mutation; AG phenotype (heterozygous), no cases showed GG phenotype. In HCV- positive patients’ group and healthy controls none were positive for the CTNNB1 mutation all showed wild AA genotype. No significant differences in the genotype (AA, AG, GG) distribution between HCC and non-HCC groups (χ2=3.619, p = 0.0571). The frequency of AA vs AG + GG genotype was considerably higher in cases when compared to controls however no statistical significance was detected (χ2=3.619, p = 0.0571). Distribution of A vs G allele in cases compared to controls showed statistically significant difference (χ2=4.571, p = 0.0325).

Conclusion

In this study we were not able to prove the clinical utility of CTNNB1 rs121913412 in Egyptian HCC patients. Further large multi-centric studies are needed to explore the clinical utility of ctDNA in assessment of tumor-specific hotspot somatic mutations in genes including CTNNB1, TERT and TP53 genes that can be identified in the peripheral blood of HCC patients. Comparison studies utilizing both ctDNA and DNA extracted from HCC tissue samples are recommended.
Effect of TAMSULOSIN on Sexual Dysfunction in Patients Complaining of Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia
Authors: El-Zayat Tarek Mostafa , Mahmoud Mahmoud Ahmed , Eissa Azab Shady Kamal
Published: July 2024

Background

Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and Erectile Dysfunction are common disorders of advancing age.

Aim and Objectives

The aim of the study was to assess the effect of Tamsulosin on sexual function in patients complaining of LUTS suggestive of BPH.

Subjects and Methods

We evaluated the sexual function, erectile & ejaculatory, of patients enrolled in the study using validated questionnaires. This evaluation was done before treatment with Tamsulosin and 3 months later, comparing the Pre & Post-Treatment scores.

Results

There was a statistically significant deterioration of orgasmic function domain of IIEF between Pre & Post-Treatment. However, no significant changes were noticed with the other IIEF domains. Also according to the MSHQ-EjD-SF, there was a significant deterioration in the ejaculation domain and ejaculation bother domain.

Conclusion

Tamsulosin was found to be with higher risk for decreasing the orgasmic frequencies and the ejaculation for patients suffering from BPH.
Gemcitabine versus Bacillus Calmette-Guérin (BCG) in Non Muscle Invasive Transitional Cell Carcinoma of the Bladder after Trans-Urethral Resection
Authors: El Zayat Tarek Mostafa , Mahmoud Mahmoud Ahmed , Elawady Hossam Mohamed , Toma Michael Saed
Published: July 2024

Background

To overcome Bacillus Calmette–Guérin (BCG) shortage and its side effect several studies have compared the safety and efficacy of intravesical gemcitabine with (BCG) for non-muscle invasive bladder cancer. The aim of this work is to evaluate the efficacy of Gemcetabine as a local intravesical treatment of superficial TCC in reducing the risk of recurrence and progression after TURBT in comparison to BCG.

Patients and Methods

This single blind controlled randomized study Included 82 patients which randomly divided into 2 groups by 1:1 method.Each group included 41 patients, group I will receive gemcitabine. Group II will receive BCG.These patients were diagnosed with superficial bladder tumor (TCC) after TURBT. These patients were followed in the out-patient clinic in the Department of Urology Ain Shams University Hospital and 6th October Health Insurance Hospital during the period from 2017 till 2021.

Results

After 1 year of follow up 67.6% of group I on the other hand 63.4% of group II were free of tumors. As regard tumor progression, only 2.7% of group I patient had tumor progression while 4.9% of group II had tumor progression but all of these results were statistically not-significant with P. value 0.475. As regard side effects after 1 year of follow up. Regarding dysuria 24 patients 96% in group (I) complained of mild dysuria. On the other hand, 39 patients 95.1 % in group (II) complained of dysuria, 9 of them 21.9 % had sever dysuria and 30 patients 73.2 % had mild dysuria. which was statistically not significant with P. value 0.078. Urine analysis was done after treatment. 33 patients (89.2%) had pus cells in the patients of group I while in group II, all patients had pus cells in urine analysis, which was statistically significant with (P. value 0.046).

Conclusion

Gemcitabine was associated with nearly similar efficacy and a clinically significant better toxicity profile compared with BCG. Intravesical gemcitabine is a promising drug that may be an option in treating patients with non muscle invasive bladder cancer.
Combined Genome-Wide Association Study and Transcriptome Analysis Reveal Candidate Genes for Resistance to Rust (Puccinia graminis) in Dactylis glomerata
Authors: Jin Yarong , Feng Guangyan , Luo Jinchan , Yan Haidong , Sun Min , Jing Tingting , Yang Yuchen , Jia Jiyuan , Zhu Xin , Wang Xiaoshan , Zhang Xinquan , Huang Linkai
Published: July 2024

Rust disease is a common plant disease that can cause wilting, slow growth of plant leaves, and even affect the growth and development of plants. Orchardgrass (Dactylis glomerata L.) is native to temperate regions of Europe, which has been introduced as a superior forage grass in temperate regions worldwide. Orchardgrass has rich genetic diversity and is widely distributed in the world, which may contain rust resistance genes not found in other crops. Therefore, we collected a total of 333 orchardgrass accessions from different regions around the world. Through a genome-wide association study (GWAS) analysis conducted in four different environments, 91 genes that overlap or are adjacent to significant single nucleotide polymorphisms (SNPs) were identified as potential rust disease resistance genes. Combining transcriptome data from susceptible (PI292589) and resistant (PI251814) accessions, the GWAS candidate gene DG5C04160.1 encoding glutathione S-transferase (GST) was found to be important for orchardgrass rust (Puccinia graminis) resistance. Interestingly, by comparing the number of GST gene family members in seven species, it was found that orchardgrass has the most GST gene family members, containing 119 GST genes. Among them, 23 GST genes showed significant differential expression after inoculation with the rust pathogen in resistant and susceptible accessions; 82% of the genes still showed significantly increased expression 14 days after inoculation in resistant accessions, while the expression level significantly decreased in susceptible accessions. These results indicate that GST genes play an important role in orchardgrass resistance to rust (P. graminis) stress by encoding GST to reduce its oxidative stress response.
Reliability of a Modified Watson-Jones Classification for Tibial Tubercle Fractures in Children
Authors: Bradley Taylor , Crowe Mary , Mayassi Hani , Patel Jay , Tamai Junichi , Mehlman Charles T.
Published: July 2024

Objectives:

The first case report describing a pediatric fracture of the tibial tubercle was published in 1852 in the Medical Times and Gazette, a Journal of Medical Science, literature, criticism, and news. A century later, in 1955, Sir Watson-Jones introduced the first classification system for this fracture. Despite the existence of several classification systems for pediatric tibial tubercle fractures in the medical literature, a crucial aspect of their validation—reliability and reproducibility—has not yet been systematically evaluated.

Methods:

In this study, a modified Watson-Jones (mWJ) classification system of tibial tubercle fractures in children was assessed for intraobserver and interobserver variability. Using the mWJ classification, 3 board-certified pediatric orthopaedic surgeons and 3 orthopaedic surgery residents, classified thirty tibial tubercle fractures based on anteroposterior and lateral radiographs on 2 separate occasions in a 2-week duration. Further comparison was made to evaluate the impact of advanced imaging, specifically computed tomography or magnetic resonance imaging, on diagnostic reliability and reproducibility.

Results:

The study found substantial intraobserver reliability of the mWJ classification based on radiographs alone, with a Cohen weighted kappa (κw) coefficient of 0.733. When advanced imaging was utilized, the reliability of the classification improved to κw = 0.783. Similarly, interobserver reliability demonstrated substantial consistency among observers when using radiographs alone (κw = 0.69) and improved agreement with advanced imaging (κw = 0.75). Notably, there was no significant difference in reliability scores between senior-level attendings and residents when analyzed as separate groups.

Conclusion:

Fracture classification systems are clinically relevant tools that help organize and transfer knowledge efficiently, provide treatment guidance, propose prognostic expectations, and improve communication in academic literature. The present study demonstrated substantial reproducibility of an mWJ fracture classification system both between and within individual surgeon raters.

Level of Evidence:

Level III—diagnostic.
The Law of Diminishing Returns in the Integrated Plastic Surgery Residency Match: A Deeper Look at the Numbers
Authors: Elemosho Abdulaziz , Sarac Benjamin A. , Janis Jeffrey E.
Published: July 2024

Background:

The highly competitive nature of the integrated plastic surgery residency match justifies the need for objective data that provide insights into some of the residents’ selection criteria. Many studies have sought to provide information on these criteria, but to our knowledge, none has described the inflection point where the match probability does not further increase. Although our study provides this information to potential applicants, it will also help them assess and optimize their chances of a successful match.

Methods:

We pooled and analyzed the data available on matched and unmatched integrated plastic surgery applicants on the national residency match program database between 2016 and 2022.

Results:

Step 2 score of 250 or more (P < 0.0001), number of publications more than 15 (P = 0.0007), number of research experiences five or more (P = 0.018), number of contiguous ranks more than 10 (P < 0.0001), number of volunteer experiences five or more (P < 0.0001), being a US MD applicant (P < 0.0001), and Alpha Omega Alpha membership (P < 0.0001) were all associated with increased probability of matching into the integrated plastic surgery program. Match probability did not further increase after 15 publications, five research experiences, 15 contiguous ranks, and 10 volunteer experiences have been reached. Having a PhD (P = 0.149) or a non-PhD graduate degree (P = 0.07) was not associated with increased match probability.

Conclusion:

The law of diminishing returns sets in for applicants to the integrated plastic surgery match after 15 publications, 15 contiguous ranks, five research experiences, and 10 volunteer experiences have been reached.
Advantages of cryopreservation for fertility preservation due to age-related fertility loss
Authors: Dafopoulos Konstantinos
Published: July 2024

The global trend of reproductive delay combined with age-related fertility loss may result in involuntary childlessness. The method of oocyte vitrification for fertility preservation as a prevention of age-related fertility loss is both safe and highly efficient. Among the many advantages of this strategy for women, the enhancement of reproductive autonomy, sex equality, the increased likelihood of future delivery of their genetically own offspring, and the cost-effectiveness are included.
Publication bias in clinical trials in cataract therapies: implications for evidence-based decision-making
Authors: Paturu Tejasvi , Shukla Anchal , Shivan Shreya Gitanjali , Benyahia Steven A. , Lippert Trenton , Velanovich Vic
Published: July 2024

Evidence-based decision-making is generally based on published evidence. Therefore, if the published evidence is biased, so will the decision-making. One possible bias is the “positive-results” publication bias. This study attempts to characterize this phenomenon in cataract therapy trials. Studies were categorized as “positive” if their results were congruent with the hypothesis and “negative” if not. Secondary outcomes included the influence of funding source and differences in publication metrics between “positive” and “negative” publications. The U.S. National Library of Medicine Clinical Trials database was reviewed for cataract trials, yielding 248 trials. Trials with less than 2 treatment arms, less than 5 participants, or insufficient reporting were excluded. Data were collected on intervention, treatment arms, funding type, publication rates, citation rate, and the impact factor/H-index of journals. Of the 132 trials included, there were 69 positive and 63 negative results. Publication rate for positive results (71%) was significantly greater than negative results (17%) (P < .01), with no significant difference in the other publication metrics. In conclusion, “negative” result trials are published less frequently, but are equally valued, if published. There are implications for evidence-based medicine with these findings.
Anxiety Symptoms and Disease Severity in Parkinson Disease
Authors: Whitmarsh Ainslie , Protea Suzy , Gibson Jessie S.
Published: July 2024

BACKGROUND: Anxiety is prevalent in Parkinson disease (PD), negatively affecting quality of life for patients and their families. Targeted anxiety interventions are needed that account for variables such as disease severity; however, there is insufficient evidence regarding the trajectory of anxiety along the disease course. OBJECTIVE: The aim of this study was to investigate the association between disease severity and anxiety symptoms in a PD sample. METHODS: This descriptive study used secondary data analyses of data from a web-based survey study of individuals with PD in the United States. Participants were 21 years or older, had access to the Internet, and were given a diagnosis of PD (N = 72). We performed multiple regression analyses to assess the relationship between patient-reported disease severity and anxiety symptoms. RESULTS: There was a statistically significant association between disease severity and anxiety symptoms in people with PD, after controlling for all 5 explanatory variables (sex, age, wearing off, disease severity, and disease duration) (P < .001). Age and wearing off PD medication also had statistically significant, although smaller, effects on anxiety symptoms (P < .05). CONCLUSION: Disease severity was related to increased anxiety symptoms among individuals with PD. Anxiety intervention research is needed, and future studies should account for variations in disease severity and medication effects in both intervention and study design.
Wildland Firefighter Work History and Clinical Indicators of Cardiovascular Health
Authors: Hasan Md. Zahid , Semmens Erin O. , Navarro DuBose Kathleen , McCray L. Kaili , Noonan Curtis W.
Published: July 2024

Objective

To determine the association between the occupational history as a wildland firefighter (WFF) and clinical indicators of cardiovascular health.

Methods

Among 2862 WFFs, we evaluated associations between the number of total days assigned on fire and high-risk categories of three clinically measured cardiovascular indicators.

Results

Almost one-third (32%) of WFFs had one or more clinical measures that would place them in high-risk categories for body mass index, blood pressure, and total cholesterol. WFF work history was associated with some of these measures: odds ratio (and 95% confidence interval) for highest versus lowest tertile of days on fire were 1.4 (1.2, 1.8) and 1.2 (1.0, 1.5) for high-risk categories of body mass index and cholesterol, respectively.

Conclusion

More frequent screening and targeted health promotion programs for WFFs are warranted to increase awareness of cardiovascular risk and prevention strategies.
Quality Assessment of a Virtual Post Offer Placement Assessment in Employee Occupational Health Services
Authors: Minter Sarah , Hainy Caitlin , Swift Melanie , Yee Claire , Meyers Jon , Nos Anna , Breeher Laura
Published: July 2024

Objective

The rise in remote work and increased access to technology allow opportunity for virtual onboarding. The aim of this project was to assess the quality of virtual onboarding versus the traditional in-person onboarding.

Methods

A multidisciplinary team utilized a survey to evaluate staff and new hire candidate satisfaction with the in-person versus virtual post offer placement assessment (POPA).

Results

The virtual POPA process maintained a high-level of quality and satisfaction among new hire healthcare candidates compared to in-person onboarding, with shorter appointment times. Employee Occupational Health Services staff and new hire candidates reported a preference for the virtual POPA process over traditional in-person onboarding.

Conclusions

The virtual POPA option reduced the length of appointments and maintained satisfaction and quality of service.
Clinical Outcomes of Endoscopic Butterfly Inlay Cartilage Myringoplasty
Authors: Joo Hye Ah , Choi Hyeon Chang , Lee Dong Kyu , Ahn Joong Ho , Park Hong Ju , Chung Jong Woo , Kang Woo Seok
Published: July 2024

Objective

To review a 3-year case series of endoscopic butterfly inlay cartilage myringoplasty performed by a single surgeon (W.S.K.) and analyze the clinical surgical outcomes.

Study Design

Retrospective study.

Setting

Tertiary care academic center.

Patients

We enrolled 60 ears with tympanic membrane (TM) perforation, receiving endoscopic inlay butterfly myringoplasty between 2019 and 2022.

Main outcomes and Measures

We reviewed patients' demographics, size and location of TM perforation, operation time, complications, and postoperative pain evaluated by the numerical rating scale (NRS). We analyzed the graft uptake success rate in 5 weeks and the perforation closure rate in 4 months after surgery. We also compared the air-bone gap (ABG) before and after the surgery.

Results

Among the 60 ears included, the mean age was 57.0 years, and 78.3% (47 of 60) had small perforations. The average operation time was 48.9 ± 11.5 minutes, and the postoperative NRS was 2.0 ± 1.6. The immediate graft uptake success rate evaluated at postoperative 5 weeks was 96.7% (58 of 60), with myringitis occurring in three ears. Except for 11 patients lost to follow-up, the perforation closure rate evaluated at postoperative 4 months was 100% (49 of 49). The mean ABG significantly improved from preoperative status (8.87 ± 5.51 dB HL) to postoperative 4 months (6.22 ± 6.03 dB HL) (p = 0.019).

Conclusions

A single surgeon's success rate for endoscopic butterfly inlay cartilage myringoplasty was almost 100%. This surgical procedure is safe and effective, with a high graft success rate.
Management of Bleeding and Thrombotic Complications During Pediatric Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference
Authors: Rintoul Natalie E. , McMichael Ali B.V. , Bembea Melania M. , DiGeronimo Robert , Patregnani Jason , Alexander Peta M.A. , Muszynski Jennifer A. , Steffen Katherine , Gehred Alison , Lyman Elizabeth , Cheifetz Ira M. ,   for the Pediatric Extracorporeal Membrane Oxygenation (ECMO) Anticoagulation Collaborative (PEACE), in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric ECMO subgroup of PALISI and the Extracorporeal Life Support Organization (PediECMO)
Published: July 2024

OBJECTIVES:

To derive systematic-review informed, modified Delphi consensus regarding the management of bleeding and thrombotic complications during pediatric extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE Consensus Conference.

DATA SOURCES:

A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021.

STUDY SELECTION:

The management of bleeding and thrombotic complications of ECMO.

DATA EXTRACTION:

Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Twelve references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form.

DATA SYNTHESIS:

Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. Two good practice statements, 5 weak recommendations, and 18 consensus statements are presented.

CONCLUSIONS:

Although bleeding and thrombotic complications during pediatric ECMO remain common, limited definitive data exist to support an evidence-based approach to treating these complications. Research is needed to improve hemostatic management of children supported with ECMO.
Recommendations on Monitoring and Replacement of Antithrombin, Fibrinogen, and Von Willebrand Factor in Pediatric Patients on Extracorporeal Membrane Oxygenation: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference
Authors: Zantek Nicole D. , Steiner Marie E. , Teruya Jun , Kreuziger Lisa Baumann , Raffini Leslie , Muszynski Jennifer A. , Alexander Peta M. A. , Gehred Alison , Lyman Elizabeth , Watt Kevin ,   for the Pediatric ECMO Anticoagulation CollaborativE (PEACE), in collaboration with the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric ECMO subgroup of PALISI and the Extracorporeal Life Support Organization (PediECMO)
Published: July 2024

OBJECTIVES:

To derive systematic review informed, modified Delphi consensus regarding monitoring and replacement of specific coagulation factors during pediatric extracorporeal membrane oxygenation (ECMO) support for the Pediatric ECMO Anticoagulation CollaborativE.

DATA SOURCES:

A structured literature search was performed using PubMed, Embase, and Cochrane Library (CENTRAL) databases from January 1988 to May 2020, with an update in May 2021.

STUDY SELECTION:

Included studies assessed monitoring and replacement of antithrombin, fibrinogen, and von Willebrand factor in pediatric ECMO support.

DATA EXTRACTION:

Two authors reviewed all citations independently, with conflicts resolved by a third reviewer if required. Twenty-nine references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form.

DATA SYNTHESIS:

Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. A panel of 48 experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. We developed one weak recommendation and four expert consensus statements.

CONCLUSIONS:

There is insufficient evidence to formulate recommendations on monitoring and replacement of antithrombin, fibrinogen, and von Willebrand factor in pediatric patients on ECMO. Optimal monitoring and parameters for replacement of key hemostasis parameters is largely unknown.
TRPS1 Is Consistently Expressed in Hidradenoma Papilliferum
Authors: Velthof Lars , Van Dorpe Jo , Tummers Philippe , Creytens David , Van de Vijver Koen
Published: July 2024

TRPS1 is a novel immunohistochemical marker, so far quite specific and sensitive for breast cancer and especially useful for the diagnosis of triple-negative breast cancer. TRPS1 expression has recently been reported in normal skin appendages, as well as in a variety of benign and malignant cutaneous tumors, including adnexal tumors. However, it has not yet been reported in hidradenoma papilliferum (papillary hidradenoma), a benign adnexal neoplasm, accepted to originate from mammary-like glands in the vulvar or anogenital region of middle-aged women. We report consistent nuclear expression of TRPS1 in the epithelium of 9/9 cases of hidradenoma papilliferum, while in 2/2 cases with foci of oxyphilic metaplasia, these foci were consistently negative for TRPS1 immunohistochemistry. Our findings are in line with the theory that hidradenoma papilliferum is derived from mammary-like glands and showed that TRPS1 can be an additional sensitive immunohistochemical marker for hidradenoma papilliferum.
Comparing Prefabricated and 3D Printed Foot Orthoses for the Management of Flat Foot Condition: A Randomized Controlled Trial
Authors: Bari Abu Zeeshan , Ahmed Naveed , Farhan Muhannad , Al-Shenqiti Abdullah , Zafar Muhammad Sohail
Published: July 2024

Objective

To investigate the short-term effects of 3D-printed and prefabricated foot orthoses on the management of flat feet.

Design

In this single-blinded study, 63 patients with flat feet were enrolled via convenience sampling. They were randomly assigned to the control and experimental groups, receiving prefabricated and customized 3D-printed foot orthoses, respectively. The assessment tools included a Visual analog scale (VAS) and a modified Quebec User Evaluation of Satisfaction with Assistive Technology (QUEST) questionnaire. The patients scored their pain at weeks 0 and 4 using the VAS. At the end of week 4, patients completed the modified version of the QUEST questionnaire to record their satisfaction with the orthosis.

Results

VAS scores at week 0 for the two groups were not statistically significant (p > 0.05). At week 4, the VAS scores of the experimental group reduced significantly (p < 0.001), whereas the VAS scores of the control group remained statistically insignificant (p > 0.05). Modified QUEST questionnaire analysis revealed higher satisfaction with orthosis comfort and effectiveness in the experimental group than in the control, while factors like orthosis dimensions, weight, and durability did not differ significantly between groups.

Conclusions

Customized 3D-printed orthoses effectively reduced pain and enhanced patient satisfaction with comfort and effectiveness in 4 weeks.
Comparison of combined virtual reality combined with standing balance training vs. standard practice in patients with hemiplegia: A single-blinded, randomized controlled trial.
Authors: Xu Yan , Yao Jiajia , Ni Jiadong , Yang Yajing , Fu Lianhui , Xu Cong
Published: July 2024

Objective

To determine whether virtual reality (VR)-based dynamic standing balance training improves three elements of sensory integration and investigate whether VR-based dynamic standing balance training results in improved outcomes, especially regarding balance and gait, compared to the standard training method.

Design

This single-blinded, randomized, controlled trial involved 30 patients with hemiplegia. The experimental (EG, n = 15) and control (CG, n = 15) groups received VR augmented-standing balance training or standard standing balance training, respectively, for 20 minutes, 5 days a week, for 3 weeks. The patients were assessed for primary (Sensory Organization Test [SOT] and the Berg balance scale [BBS]) and secondary (the functional reaching test and timed up-and-go test [TUG]) outcomes before and after training.

Results

From preintervention to postintervention, the BBS score (F = 26.295, p < 0.05), TUG score (F = 18.12, p < 0.05), mean score of conditions 2 (F = 4.36, p < 0.05) and 6 (F = 5.61, p < 0.05), and composite score of the SOT (F = 5.385, p < 0.05) in both groups were significantly improved. However, there was no significant difference between EG and CG (time*group p > 0.05).

Conclusion

VR combined with standing balance training improved sensory integration, postural control, balance, and gait ability in patients with hemiplegia, reducing fall risk. However, outcomes were comparable to general balance training regarding balance and gait.
Selection for early reproduction leads to accelerated aging and extensive metabolic remodeling inDrosophila melanogaster
Authors: Hubert David L. , Arnold Kenneth R. , Greenspan Zachary G. , Pupo Anastasia , Robinson Ryan D. , Chavarin Valeria V. , Barter Thomas B. , Djukovic Danijel , Raftery Daniel , Vue Zer , Hinton Antentor , McReynolds Melanie R. , Harrison Benjamin R. , Phillips Mark A.
Published: July 2024

Experimental evolution studies that feature selection on life-history characters are a proven approach for studying the evolution of aging and variation in rates of senescence. Recently, the incorporation of genomic and transcriptomic approaches into this framework has led to the identification of hundreds of genes associated with different aging patterns. However, our understanding of the specific molecular mechanisms underlying these aging patterns remains limited. Here, we incorporated extensive metabolomic profiling into this framework to generate mechanistic insights into aging patterns inDrosophila melanogaster. Specifically, we characterized metabolomic change over adult lifespan in populations ofD. melanogasterwhere selection for early reproduction has led to an accelerated aging phenotype relative to their controls. Using these data we: i) evaluated evolutionary repeatability across the metabolome; ii) assessed the value of the metabolome as a predictor of “biological age” in this system; and iii) identified specific metabolites associated with accelerated aging. Generally, our findings suggest that selection for early reproduction resulted in highly repeatable alterations to the metabolome and the metabolome itself is a reliable predictor of “biological age”. Specifically, we find clusters of metabolites that are associated with the different rates of senescence observed between our accelerated aging population and their controls, adding new insights into the metabolites that may be driving the accelerated aging phenotype.

Significance

While experimental evolution studies featuringDrosophila melanogasterhave generated significant insights into the forces that shape aging and life history patterns, more recent efforts incorporating genomic and transcriptomic data have had comparatively little success identifying the molecular mechanisms underlying these patterns. Here we work to incorporate molecular phenotyping into this general framework as a way forward. Specifically, we characterize how the metabolome changes with age in populations ofD. melanogasterwhere hundreds of generations of selection for early reproduction have led to enrichment for an accelerated aging phenotype. By comparing to control populations, we show that the metabolome does appear to capture true signals of “biological age” and provides a new avenue for understanding the factors that underlie complex trait variation in real populations.
Revolutionizing Molecular Cloning: Introducing FastCloneAssist, a Streamlined Python Tool for Optimizing Primer Design in Restriction & Ligation-Independent PCR Cloning
Authors: Singh Pradip Kumar , Donnenberg Michael S.
Published: July 2024

FastCloning, a paradigm shift in PCR cloning, has streamlined the process by eliminating laborious, multi-step traditional methods. This innovative technique, pioneered by Li et al. (2011), utilizes overlapping PCR primers and DpnI digestion for seamless integration of insert DNA into any desired vector position, regardless of restriction sites. This versatility makes FastCloning ideal for constructing fusion proteins, chimeric cDNAs, and manipulating genes with unparalleled ease.

However, efficient primer design remains a critical hurdle, particularly for newcomers, as errors can lead to failed cloning attempts. To address this bottleneck, we present FastCloneAssist, a user-friendly Python program that automates FastCloning primer design with minimal user input. Users simply provide vector and insert sequences, along with the desired melting temperature (Tm), and FastCloneAssist provides best primer pairs after calculating optimal primer parameters for efficient PCR amplification and seamless DNA integration using established bioinformatics libraries. This open-source, freely available tool simplifies and accelerates cloning, making this powerful technique accessible to researchers of all levels and expediting scientific discovery.
Self-organizing recruitment of compensatory areas maximizes residual motor performance post-stroke
Authors: Lee Kevin , Barradas Victor , Schweighofer Nicolas
Published: July 2024

Whereas the orderly recruitment of compensatory motor cortical areas after stroke depends on the size of the motor cortex lesion affecting arm and hand movements, the mechanisms underlying this reorganization are unknown. Here, we hypothesized that the recruitment of compensatory areas results from the motor system’s goal to optimize performance given the anatomical constraints before and after the lesion. This optimization is achieved through two complementary plastic processes: a homeostatic regulation process, which maximizes information transfer in sensory-motor networks, and a reinforcement learning process, which minimizes movement error and effort. To test this hypothesis, we developed a neuro-musculoskeletal model that controls a 7-muscle planar arm via a cortical network that includes a primary motor cortex and a premotor cortex that directly project to spinal motor neurons, and a contra-lesional primary motor cortex that projects to spinal motor neurons via the reticular formation. Synapses in the cortical areas are updated via reinforcement learning and the activity of spinal motor neurons is adjusted through homeostatic regulation. The model replicated neural, muscular, and behavioral outcomes in both non-lesioned and lesioned brains. With increasing lesion sizes, the model demonstrated systematic recruitment of the remaining primary motor cortex, premotor cortex, and contra-lesional cortex. The premotor cortex acted as a reserve area for fine motor control recovery, while the contra-lesional cortex helped avoid paralysis at the cost of poor joint control. Plasticity in spinal motor neurons enabled force generation after large cortical lesions despite weak corticospinal inputs. Compensatory activity in the premotor and contra-lesional motor cortex was more prominent in the early recovery period, gradually decreasing as the network minimized effort. Thus, the orderly recruitment of compensatory areas following strokes of varying sizes results from biologically plausible local plastic processes that maximize performance, whether the brain is intact or lesioned.
Linker histone H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape
Authors: Jepsen Vera H. , Hanel Andrea , Picard Daniel , Mehtonen Juha , Hasselmann Rebecca , Schliehe-Diecks Julian , Scharov Katerina , Tu Jia-Wey , Bhave Rigveda , Kameri Ersen , Qin Nan , Wang Herui , Zhuang Zhengping , Wagener Rabea , Blümel Lena , Lautwein Tobias , Hein Daniel , Kögler Gesine , Remke Marc , Bhatia Sanil , Heinäniemi Merja , Borkhardt Arndt , Fischer Ute
Published: July 2024

ETV6::RUNX1is the most common oncogenic fusion in pediatric B cell precursor acute lymphoblastic leukemia (BCP-ALL). It induces a clinically silent preleukemic state that requires secondary mutations for progression to leukemia. However, the molecular mechanisms contributing to the characteristic quiescence ofETV6::RUNX1+ preleukemic cells remain elusive. Here, we detect factors involved in the preleukemic state by generating human induced pluripotent stem cell (hiPSC) models using CRISPR/Cas9 gene editing. We identified upregulation of linker histoneH1-0in our preleukemic models, which was preserved upon hematopoietic differentiation and transformation to BCP-ALL. ETV6::RUNX1 inducesH1-0promoter activity whereas depletion of H1-0 specifically inhibited ETV6::RUNX1 signature genes, indicating its role as a key mediator of the ETV6::RUNX1 transcriptome. Single-cell gene expression analysis revealed highH1-0levels in quiescent cells during hematopoiesis and inverse correlation with transcriptional activity. Pharmacologically, H1-0 protein levels correspond to susceptibility of BCP-ALL towards histone deacetylase inhibitors (HDACi). Altogether, our study provides novel insights into ETV6::RUNX1-induced quiescence and suggests that further investigation into combinatorial treatment of BCP-ALL using the H1-0- inducing HDACi Quisinostat may be worthwhile.
The Surgical Method of Craniectomy Differentially Affects Acute Seizures, Brain Deformation and Behavior in a TBI Animal Model
Authors: Santana-Gomez Cesar , Smith Gregory , Mousavi Ava , Shamas Mohamad , Harris Neil G. , Staba Richard
Published: July 2024

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality worldwide. Multiple injury models have been developed to study this neurological disorder. One such model is the lateral fluid-percussion injury (LFPI) rodent model. The LFPI model can be generated with different surgical procedures that could affect the injury and be reflected in neurobehavioral dysfunction and acute EEG changes. A craniectomy was performed either with a trephine hand drill or with a trephine electric drill that was centered over the left hemisphere of adult, male Sprague Dawley rats. Sham craniectomy groups were assessed by hand-drilled (ShamHMRI) and electric-drilled (ShamEMRI) to evaluate by MRI. Then, TBI was induced in separate groups (TBIH) and (TBIE) using a fluid-percussion device. Sham-injured rats (ShamH/ShamE) underwent the same surgical procedures as the TBI rats. During the same surgery session, rats were implanted with screw and microwire electrodes positioned in the neocortex and hippocampus and the EEG activity was recorded 24 hours for the first 7 days after TBI for assessing the acute EEG seizure and Gamma Event Coupling (GEC). The electric drilling craniectomy induced greater tissue damage and sensorimotor deficits compared to the hand drill. Analysis of the EEG revealed acute seizures in at least one animal from each group after the procedure. Both TBI and Sham rats from the electric drill groups had a significant greater total number of seizures than the animals that were craniectomized manually (p<0.05). Similarly, EEG functional connectivity was lower in ShamE compared to ShamH rats. These results suggest that electrical versus hand drilling craniectomies produce cortical injury in addition to the LFPI which increases the likelihood for acute post-traumatic seizures. Differences in the surgical approach could be one reason for the variability in the injury that makes it difficult to replicate results between preclinical TBI studies.