bluuebunny/crossref_metadata_2025 huggingface dataset:
Top Ten Contributions of Pediatric Hematology/Oncology to the Diagnosis and Treatment of Acute Lymphoblastic Leukemia
Authors: Miller Denis R.
Published: October 2023

Monumental progress has occurred in the diagnosis and treatment of childhood acute lymphoblastic leukemia dating back to the classic paper of Farber and colleagues in 1948. This historical review from the perspective of an individual, familiar with many of the waystations on this superhighway, will offer an admittedly personal review of the top 10 major contributions to the field. Fortunately, there have been many more additional advances beyond these 10 as we have witnessed an impressive improvement in overall survival from a few months 75 years ago to a cure rate of 85% in the world’s more advanced countries. Other workers in the field assuredly would create a different list and ranking of these advances but the takeaway summation of the make-up and order of these lists is that advances have yielded improved and prolonged responses, a rational understanding of factors, both clinical and biological, that predict response and prognosis, the application of those factors to tailor therapy’s intensity and duration to those factors and to discover and design modalities and targets of therapy that target our much more complete understanding of this most common malignancy of infants and children. On a very personal note, I vividly recall an early, ill-advised decision to devote my academic career to hematology/oncology, with one glaring exception, acute lymphoblastic leukemia, and other malignancies. The stark realities of clinical practice and the harsh unmet needs and mostly unanswered challenges redirected my path that resulted in participation in many of these advances, making my own journey so gratifying and that of most of our patients so favorable.
Sexual Distancing During 5 Periods Around and During the COVID-19 Pandemic, Amsterdam, the Netherlands
Authors: de Vries Dominique C. , Jongen Vita W. , Zimmermann Hanne M.L. , Davidovich Udi , Hoornenborg Elske , de Vries Henry J.C.
Published: October 2023

Background

Social and sexual distancing (ie, abstaining from sex with persons outside one's household) was important in the control of the COVID-19 pandemic. Compliance to distancing measures can change over time. We assessed changes in compliance to the sexual distancing measures during five periods of the COVID-19 pandemic in the Netherlands.

Methods

Between November 2021 and March 2022, we used a structured questionnaire containing questions about sexual behavior and factors that could have influenced compliance with sexual distancing. Variables related to sexual behavior were measured for 5 periods, before and during the pandemic, delineated by imposement and relaxation of lockdown measures.

Results

Eight hundred seventy participants (predominantly MSM) completed the questionnaire. We found that compliance to the sexual distancing measures decreased over time. The number of casual partners was highest after the lockdown measures were relaxed for the second time (April 2021 to March 2022), and even higher than before the first lockdown. Factors positively associated with sexual distancing compliance were: having confidence in the information provided by the government and experiencing less or similar need for physical contact compared with before the pandemic. Factors that lowered compliance over time were: previously having had COVID-19, perceiving the lockdown measures as overstated, having sex with casual partners and similar drug use during the pandemic as before.

Conclusions

Our findings suggest that sexual distancing measures are difficult to maintain for a long period. Other measures, such as confinement to a small network of known partners, might be more effective for longer pandemics in minimizing the spread of infectious diseases.
Qualitative Point-of-Care Ultrasound Enema Management for Constipation
Authors: Riera Antonio , Phatak Uma P.
Published: October 2023

We discuss 10 cases where the qualitative evaluation of hard stool in the rectum with point-of-care ultrasound helped guide enema administration in a pediatric emergency department. Point-of-care ultrasound findings were especially valuable in cases where the presenting symptoms were undifferentiated, a language barrier was present, or the guardian and child denied that constipation was an active problem. When sodium phosphate enema administration was done in the pediatric emergency department, evacuation of the rectal stool burden was observed in most cases before final disposition.
Leveraging social networks for identification of people with HIV who are virally unsuppressed
Authors: Cummins Breschine , Johnson Kara , Schneider John A. , Del Vecchio Natascha , Moshiri Niema , Wertheim Joel O. , Goyal Ravi , Skaathun Britt
Published: October 2023

Objectives:

This study investigates primary peer-referral engagement (PRE) strategies to assess which strategy results in engaging higher numbers of people with HIV (PWH) who are virally unsuppressed.

Design:

We develop a modeling study that simulates an HIV epidemic (transmission, disease progression, and viral evolution) over 6 years using an agent-based model followed by simulating PRE strategies. We investigate two PRE strategies where referrals are based on social network strategies (SNS) or sexual partner contact tracing (SPCT).

Methods:

We parameterize, calibrate, and validate our study using data from Chicago on Black sexual minority men to assess these strategies for a population with high incidence and prevalence of HIV. For each strategy, we calculate the number of PWH recruited who are undiagnosed or out-of-care (OoC) and the number of direct or indirect transmissions.

Results:

SNS and SPCT identified 256.5 [95% confidence interval (CI) 234–279] and 15 (95% CI 7–27) PWH, respectively. Of these, SNS identified 159 (95% CI 142–177) PWH OoC and 32 (95% CI 21–43) PWH undiagnosed compared with 9 (95% CI 3–18) and 2 (95% CI 0–5) for SPCT. SNS identified 15.5 (95% CI 6–25) and 7.5 (95% CI 2–11) indirect and direct transmission pairs, whereas SPCT identified 6 (95% CI 0–8) and 5 (95% CI 0–8), respectively.

Conclusion:

With no testing constraints, SNS is the more effective strategy to identify undiagnosed and OoC PWH. Neither strategy is successful at identifying sufficient indirect or direct transmission pairs to investigate transmission networks.
Noncontrast Myocardial Characterization in Acute Myocardial Infarction Using Electron Density Imaging
Authors: Rodriguez-Granillo Gaston A. , Cirio Juan , Vila Jose F. , Langzam Eran , Ivanc Thomas , Fontana Lucia , Descalzo Amalia , Rubilar Bibiana , Lylyk Pedro
Published: October 2023

Purpose:

Spectral computed tomography (CT) enables improved tissue characterization, although virtually all research has focused on contrast-enhanced examinations. We hypothesized that changes in myocardial tissue related to acute myocardial infarction (AMI) might potentially be identified without the need for contrast administration using electron density (ED) imaging.

Patients and Methods:

This retrospective observational study involved a small series (n = 15) of patients admitted to our institution with a first AMI without signs of hemodynamic instability and identification of a culprit vessel with invasive coronary angiography during the same admission, who also underwent a noncontrast, low-dose chest CT using a dual-layer spectral CT scanner. Images were assessed in search of dark areas with low density on ED imaging, and the mean percentage ED relative to water (%EDW) was calculated.

Results:

Using a qualitative approach, ED assessment enabled the identification of 11/15 (73%) affected coronary territories, with a sensitivity of 73% (95% CI: 45; 92%) and a specificity of 87% (95% CI: 69; 96%). AMI segments showed significantly lower ED values than the remote myocardium (103.8 ± 0.8 vs 104.3 ± 0.6 %EDW, P < 0.0001), and a threshold below 103.9 %EDW had a sensitivity of 66% and specificity of 79% for the identification of AMI. In a control group of patients without a history of cardiovascular disease, none had areas with focal reduction of ED following the shape of the myocardial wall.

Conclusions:

In our preliminary series, ED imaging showed the potential to enable the identification of myocardial tissue changes related to AMI without iodinated contrast requirement.
Application of a Novel Miniaturized Histopathologic Microscope for Ex Vivo Identifying Cerebral Glioma Margins Rapidly During Surgery: A Parallel Control Study
Authors: Wu Weichi , Xie Baoshu , Zhang Xiaowei , Zheng Chen , Sun Huixin , Jiang Mingyang , Hu Tiefeng , Liu Xinman , Zhang Nu , He Kejun
Published: October 2023

Purpose:

The purpose of our study is to assess the clinical performance of the DiveScope, a novel handheld histopathologic microscope in rapidly differentiating glioma from normal brain tissue during neurosurgery.

Methods:

Thirty-two ex vivo specimens from 18 patients were included in the present study. The excised suspicious tissue was sequentially stained with sodium fluorescein and methylene blue and scanned with DiveScope during surgery. The adjacent tissue was sent to the department of pathology for frozen section examination. They would eventually be sent to the pathology department later for hematoxylin and eosin staining for final confirmation. The positive likelihood ratio, negative likelihood ratio, sensitivity, specificity, and area under the curve of the device were calculated. In addition, the difference in time usage between DiveScope and frozen sections was compared for the initial judgment.

Results:

The sensitivity and specificity of the DiveScope after analyzing hematoxylin and eosin -staining sections, were 88.29% and 100%, respectively. In contrast, the sensitivity and specificity of the frozen sections histopathology were 100% and 75%, respectively. The area under the curve of the DiveScope and the frozen sections histopathology was not significant (P=0.578). Concerning time usage, DiveScope is significantly much faster than the frozen sections histopathology no matter the size of tissue.

Conclusion:

Compared with traditional pathological frozen sections, DiveScope was faster and displayed an equal accuracy for judging tumor margins intraoperatively.
Patient Satisfaction and Radiologic Assessability After Treatment of Complex Skull Defects With a Custom-Made Cranioplasty From a Thin Titanium Sheet
Authors: Lewitz Marc , Fischer Sandra , Nakamura Makoto , Ewelt Christian , Fortmann Thomas , Wilbers Eike , Sarkis Hraq , Stroop Ralf , Cinibulak Zafer , Welzel Saravia Heinz , Sakellaropoulou Ioanna , Grabowski Steffen , Rahim Tamim , Zawy Alsofy Samer
Published: October 2023

Objective:

The cosmetically good coverage of skull defects is a challenge in neurosurgical clinics. In addition, the skull treated with implants and the underlying structures must remain radiologically assessable. In this examination, the postoperative courses of patients after implantation of CranioTop is described. Digital x-ray, computed tomography, and magnetic resonance images after implantation of CranioTop were evaluated with regard to their assessability.

Materials and Methods:

Between 2018 and 2020, 23 titanium cranioplasties (CranioTop) were implanted to 21 patients. The intraoperative handling, the accuracy of fit, the healing process, the cosmetic result and the physical condition of the patients were examined. In addition, digital x-rays, magnetic resonance imaging, and computed tomography scans of the cranium supplied with CranioTop were examined.

Results:

The evaluation showed good to very good results regarding patients’ satisfaction. There were no severe complications; thirteen patients found the cosmetic result very good; 8 patients assessed the cosmetic result as good. Because of the low thickness and density of the CranioTop plastic there was only low formation of radial stripe artifacts (streaking) and susceptibility artifacts. The assessment of digital x-ray, computed tomography, and magnetic resonance imaging images is possible after implantation of CranioTop.

Conclusion:

The patients treated with CranioTop showed a high level of satisfaction with regard to the cosmetic result and their physical condition. Furthermore, the cranium supplied with CranioTop remains well assessable in radiologic imaging with only slight limitations in magnetic resonance imaging.
Thematic Analysis of Parental Experiences of Patients’ Orthognathic Surgery
Authors: Johns Alexis , Zukin Julia , Odono Lauren , Cardenas Ana Karin , Baird Jennifer , Clarke Noreen
Published: October 2023

Orthognathic surgery often requires extensive orthodontic preparation and a prolonged postoperative recovery that can be stressful for patients and their families. Parents are a primary source of support for patients; accordingly, a better understanding of the parents’ experience of orthognathic surgery can help inform clinical care. Using a prospective cross-sectional qualitative study design, 4 focus groups (2 English and 2 Spanish; mean length 65 min) were held with parents of patients who had completed orthognathic surgery for class II/III malocclusion. Thematic content analysis of the group transcriptions was conducted. Participants were 10 mothers and 3 fathers of 12 children (50% with cleft lip/palate) ages 17 to 23 who completed LeFort I (41.7%), LeFort I with bilateral sagittal split osteotomy (BSSO; 41.7%), or BSSO (16.7%) within the prior 3 to 16 months. Themes fit within a chronological framework: (1) Preparing for Surgery included their larger health context, anticipating surgery, surgery preparation by team and family, and religious faith; (2) Challenges after Surgery consisted of complications, pain, frustration, nutritional challenges, parental anxiety, activity changes, sleep, breathing issues, swelling, and unanticipated aspects of surgery; and (3) Supports after Surgery were nutritional support, appreciation of medical team, postoperative improvements, appearance changes, communicating, supporting patient, and patient coping. Parents also offered advice for families and medical teams. Surgeons and other providers who are part of orthognathic surgical preparation can implement recommendations based on parental experiences to increase patient and family readiness for surgery by providing early education, assisting with advocacy, focusing on nutrition, and supporting coping.
Incidence of Airway Abnormalities in Children With Craniosynostosis
Authors: Eitan Dana , Bhuskute Aditi , Scheffler Patrick
Published: October 2023

Introduction:

Children with syndromic craniosynostosis are known to have a high propensity for associated airway abnormalities. However, this has not been investigated using a large-scale national database.

Methods:

For this retrospective cohort study, the 2016 Healthcare Cost and Utilization Project Kid’s Inpatient Database was queried for craniosynostosis patients. Data on demographics, airway diagnoses, and comorbidities were analyzed.

Results:

Four thousand nine hundred fourteen children with craniosynostosis with a mean age of 1.7±3.6 years were identified. Of these, 51% were female and 136 children had an associated syndrome. Choanal atresia was present in 31% of patients with an associated syndrome versus 2.5% without. Syndromic patients are 4.59 times more likely (95% CI 2.65–7.94) to have airway anomalies than nonsyndromic patients. After age and sex adjustment, craniosynostosis patients have higher likelihoods of presenting with other anomalies, with syndromic having higher incidences: 5.23 times (95% CI 2.63–10.39) more likely to have laryngomalacia, 18.30 times (95% CI 3.27–102.36) more likely to have tracheal stenosis, and 4.58 times (95% CI 1.36– 15.43) more likely to have tracheomalacia. Incidence of tracheostomy was 5.84 times (95% CI 3.77–9.04) higher in syndromic patients with craniosynostosis. Tracheostomy rates were 28.4% and 4.6% in craniosynostosis patients with and without associated syndrome, respectively.

Conclusion:

Syndromic craniosynostosis patients had significantly higher incidences of choanal atresia and other airway anomalies. Given a high incidence of airway anomalies, syndromic craniosynostosis patients likely warrant routine airway evaluation. Providers should also be vigilant about airway evaluation in patients with nonsyndromic craniosynostosis when aerodigestive symptoms arise.
Re-expansion Pulmonary Edema: A Rare Complication of Chest Drain Insertion in Spontaneous Pneumothorax
Authors: Bolong Mohammad Firdaus , Shanmuga Ratnam Selvendra , Raja Badrol Hisham Raja Muhammad Burhanudeen Afiq bin , Pang Tze Ping Nicholas
Published: October 2023

Re-expansion pulmonary edema (RPE) after chest drain insertion is rare. The objective of this clinical case report is to highlight the importance of this chest drain insertion complication. A 35-year-old man presented to the emergency department with a chief complaint of shortness of breath and pleuritic chest pain. Further physical examination and radiographic investigations showed a left-sided hemipneumothorax. A chest drain was inserted, but subsequently the patient developed worsening shortness of breath, desaturation, and coughed out pink frothy sputum. Repeated chest radiographic and computed tomographic thorax findings suggested RPE. A nonrebreathable mask with high-flow oxygen was given to the patient to maintain his oxygen saturation. The patient was referred to the cardiothoracic team and was admitted to the hospital. Despite conservative management in the ward, the patient underwent lung decortication. Postdecortication, the left-sided lung re-expanded well, and the patient was discharged home. This case highlighted this rare, potentially fatal complication of chest drain insertion for spontaneous pneumothorax.
Ophthalmologic Emergencies
Authors: Evans Dian Dowling , Hoyt Karen Sue
Published: October 2023

There are an estimated 2–3 million emergency department (ED) visits in the United States for eye complaints. Although most patients who present to the ED have nontraumatic eye complaints, many seek treatment for eye trauma, which is a leading cause of unilateral blindness and vison impairment. Given the prevalence of eye-related emergencies, it is imperative that emergency care providers understand how to recognize and treat eye complaints to prevent permanent vision loss and disability. This article covers basic eye anatomy and physiology, discusses a systematic approach to the eye examination, and presents the evidence-based treatment of selected, common nonemergent and emergent eye complaints. For each complaint, essential history questions, examination techniques, differentials, and emergency management have been presented.
Review of spinal cord stimulation for disorders of consciousness
Authors: Piedade Guilherme Santos , Assumpcao de Monaco Bernardo , Guest James D. , Cordeiro Joacir Graciolli
Published: October 2023

Purpose of review

High-cervical spinal cord stimulation can alter cortical activity and cerebral metabolism. These effects are potentially beneficial for disorders of consciousness. A better understanding of the effects of clinical application of stimulation is needed. We aimed to evaluate the existing literature to determine the state of available knowledge. We performed a literature review of clinical studies assessing cervical spinal cord epidural stimulation for disorders of consciousness. Only peer-reviewed articles reporting preoperative and postoperative clinical status were included.

Recent findings

Nineteen studies were included. A total of 532 cases were reported, and 255 patients were considered responsive (47.9%). Considering only studies published after the definition of minimally conscious state (MCS) as an entity, 402 individuals in unresponsive wakefulness syndrome (UWS) and 113 in MCS were reported. Responsiveness to SCS was reported in 170 UWS patients (42.3%) and in 78 MCS cases (69.0%), although the criteria for responsiveness and outcome measures varied among publications.

Cervical SCS yielded encouraging results in patients with disorders of consciousness and seems to be more effective in MCS. More extensive investigation is needed to understand its potential role in clinical practice.
Magnitude of HBV and HIV Among Women at Comprehensive Abortion Care Units and Their Knowledge, Attitude and Practice in Health Institutions in Addis Ababa, Ethiopia.
Authors: Bogale Thomas , Diriba Regasa
Published: October 2023

Introduction Human immune-deficiency virus and hepatitis B virus are highly prevalent in developing countries like Asia and Sub-Saharan Africa. Women living in this area are more vulnerable to these viruses due to lack of awareness, sexual abuse and frequent unsafe abortion. This study was aimed to determine the magnitude of HBV and HIV among women at the comprehensive abortion care units and their knowledge, attitude, and practice in Addis Ababa, Ethiopia. The objective of this study was to determine the magnitude of HBV and HIV among woman get service at comprehensive abortion care units and their knowledge, attitude and practice at selected health care center in Addis Ababa Method Across a sectional study was conducted among women at comprehensive abortion and care unit, at selected public health institutions in Addis Ababa, Ethiopia. A structured questionnaire was used to collect data on socio-demographic characteristics, knowledge, attitude, and practices via face-to-face interviews. The presence of antibodies to HIV was tested based on the national testing algorithm. Hepatitis B surface antigen was analyzed using the rapid test and positive results were confirmed ELISA kits. Results In this study, the prevalence of HBV and HIV among the study participants was 7.6% and 4.7%, respectively. From the total participants, 78.6% did not know how the disease is transmitted and believed that HBV can be transmitted through contaminated water. Conclusion Women who attend comprehensive abortion have less information and poor practice to keep themselves from these viral infections.
Radical Pair Model for Magnetic Field Effects on NMDA Receptor Activity
Authors: Nair Parvathy S , Zadeh-Haghighi Hadi , Simon Christoph
Published: October 2023

The N-methyl-D-aspartate receptor is a prominent player in brain development and functioning. Perturbations to its functioning through external stimuli like magnetic fields can potentially affect the brain in numerous ways. Various studies have shown that magnetic fields of varying strengths affect these receptors. We propose that the radical pair mechanism, a quantum mechanical process, could explain some of these field effects. Radicals of the form [RO•Mg(H2O)n+•], where R is a protein residue that can be Serine or Tyrosine, are considered for this study. The variation in the singlet fractional yield of the radical pairs, as a function of magnetic field strength, is calculated to understand how the magnetic field affects the products of the radical pair reactions. Based on the results, the radical pair mechanism is a likely candidate for explaining the magnetic field effects observed on the receptor activity. The model predicts changes in the behaviour of the system as magnetic field strength is varied and also predicts certain isotope effects. The results further suggest that similar effects on radical pairs could be a plausible explanation for various magnetic field effects within the brain.
Network-based clustering unveils interconnected landscapes of genomic and clinical features across myeloid malignancies
Authors: Bayer Fritz , Roncador Marco , Moffa Giusi , Morita Kiyomi , Takahashi Koichi , Beerenwinkel Niko , Kuipers Jack
Published: October 2023

Myeloid malignancies exhibit considerable heterogeneity with overlapping clinical and genetic features among different subtypes. Current classification schemes, predominantly based on clinical features, fall short of capturing the complex genomic landscapes of these malignancies. Here, we present a data-driven approach that integrates mutational features and clinical covariates within networks of their probabilistic relationships, enabling the discovery of de novo cancer subgroups. In a cohort of 1323 patients across acute myeloid leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia and myeloproliferative neoplasms, we identified novel subgroups that outperform established risk classifications in prognostic accuracy. Our findings suggest that mutational patterns are often shared across different types of myeloid malignancies, with distinct subtypes potentially representing evolutionary stages en route to leukemia. Within the novel subgroups, our integrative method discerns unique patterns combining genomic and clinical features to provide a comprehensive view of the multifaceted genomic and clinical landscape of myeloid malignancies. This in turn may guide the development of targeted therapeutic strategies and offers a pathway to enhanced patient stratification.
A Practical Approach for Targeting Structural Variants Genome-wide in Plasma Cell-free DNA
Authors: Murata Michael M. , Igari Fumie , Urbanowicz Ryan , Mouakkad Lila , Kim Sungjin , Chen Zijing , DiVizio Dolores , Posadas Edwin M. , Giuliano Armando E. , Tanaka Hisashi
Published: October 2023

Plasma cell-free DNA (cfDNA) is a promising source of gene mutations for cancer detection by liquid biopsy. However, no current tests interrogate chromosomal structural variants (SVs) genome-wide. Here, we report a simple molecular and sequencing workflow called Genome-wide Analysis of Palindrome Formation (GAPF-seq) to probe DNA palindromes, a type of SV that often demarcates gene amplification. With low-throughput next-generation sequencing and automated machine learning, tumor DNA showed skewed chromosomal distributions of high-coverage 1-kb bins (HCBs), which differentiated 39 breast tumors from matched normal DNA with an average Area Under the Curve (AUC) of 0.9819. A proof-of-concept liquid biopsy study using cfDNA from prostate cancer patients and healthy individuals yielded an average AUC of 0.965. HCBs on the X chromosome emerged as a determinant feature and were associated with androgen receptor gene amplification. As a novel agnostic liquid biopsy approach, GAPF-seq could fill the technological gap offering unique cancer-specific SV profiles.
Integrating population-level and cell-based signatures for drug repositioning
Authors: He Chunfeng , Xu Yue , Zhou Yuan , Fan Jiayao , Cheng Chunxiao , Meng Ran , Gamazon Eric R. , Zhou Dan
Published: October 2023

Drug repositioning presents a streamlined and cost-efficient way to expand the range of therapeutic possibilities. Furthermore, drugs with genetic evidence are more likely to progress successfully through clinical trials towards FDA approval. Exploiting these developments, single gene-based drug repositioning methods have been implemented, but approaches leveraging the entire spectrum of molecular signatures are critically underexplored. Most multi-gene-based approaches rely on differential gene expression (DGE) analysis, which is prone to identify the molecular consequence of disease and renders causal inference challenging. We propose a framework TReD (Transcriptome-informed Reversal Distance) that integrates population-level disease signatures robust to reverse causality and cell-based drug-induced transcriptome response profiles. TReD embeds the disease signature and drug profile in a high-dimensional normed space, quantifying the reversal potential of candidate drugs in a disease-related cell screen assay. The robustness is ensured by evaluation in additional cell screens. For an application, we implement the framework to identify potential drugs against COVID-19. Taking transcriptome-wide association study (TWAS) results from four relevant tissues and three DGE results as disease features, we identify 37 drugs showing potential reversal roles in at least four of the seven disease signatures. Notably, over 70% (27/37) of the drugs have been linked to COVID-19 from other studies, and among them, eight drugs are supported by ongoing/completed clinical trials. For example, TReD identifies the well-studied JAK1/JAK2 inhibitor baricitinib, the first FDA-approved immunomodulatory treatment for COVID-19. Novel potential candidates, including enzastaurin, a selective inhibitor of PKC-beta which can be activated by SARS-CoV-2, are also identified. In summary, we propose a comprehensive genetics-anchored framework integrating population-level signatures and cell-based screens that can accelerate the search for new therapeutic strategies.
Sex-specific cardiovascular risk factors in the UK Biobank
Authors: Pierre Skyler St. , Kaczmarski Bartosz , Peirlinck Mathias , Kuhl Ellen
Published: October 2023

The lack of sex-specific cardiovascular disease criteria contributes to the under-diagnosis of women compared to men. For more than half a century, the Framingham Risk Score has been the gold standard to estimate an individual’s risk of developing cardiovascular disease based on age, sex, cholesterol levels, blood pressure, diabetes, and smoking. Now, machine learning can offer a much more nuanced insight into predicting the risk of cardiovascular disease. The UK Biobank is a large database that includes traditional risk factors as well as tests related to the cardiovascular system: magnetic resonance imaging, pulse wave analysis, electrocardiograms, and carotid ultrasounds. Here we leverage 20,542 datasets from the UK Biobank to build more accurate cardiovascular risk models than the Framingham Risk Score, and quantify the under-diagnosis of women compared to men. Strikingly, for first-degree atrioventricular block and dilated cardiomyopathy, two conditions with non-sex-specific diagnostic criteria, our study shows that women are under-diagnosed 2x and 1.4x more than men. Similarly, our results demonstrate the need for sex-specific criteria in essential primary hypertension and hypertrophic cardiomyopathy. Our feature importance analysis reveals that, out of the top 10 features across three sex and four disease categories, traditional Framingham factors made up between 40-50%, electrocardiogram 30-33%, pulse wave analysis 13-23%, and magnetic resonance imaging and carotid ultrasound 0-10%. Improving the Framingham Risk Score by leveraging big data and machine learning allows us to incorporate a wider range of biomedical data and prediction features, enhance personalization and accuracy, and continuously integrate new data and knowledge, with the ultimate goal to improve accurate prediction, early detection, and early intervention in cardiovascular disease management.

Our analysis pipeline and trained classifiers are freely available athttps://github.com/LivingMatterLab/CardiovascularDiseaseClassification
C-reactive protein does not predict future depression onset in adolescents: preliminary findings from a longitudinal study
Authors: Schwartz Joshua J. , Roske Chloe , Liu Qi , Tobe Russel H. , Ely Benjamin A. , Gabbay Vilma
Published: October 2023

Introduction

Neuroinflammatory processes have been extensively implicated in the underlying neurobiology of numerous neuropsychiatric disorders. Elevated C-reactive protein (CRP), an indicator of non-specific inflammation commonly utilized in clinical practice, has been associated with depression in adults. In adolescents, our group previously found CRP to be associated with altered neural reward function but not with mood and anxiety symptoms assessed cross-sectionally. We hypothesized that the distinct CRP findings in adolescent vs. adult depression may be due to chronicity, with neuroinflammatory effects on psychiatric disorders gradually accumulating over time. Here, we conducted a longitudinal study to evaluate if CRP levels predicted future onset or progression of depression in adolescents.

Methods

Participants were 53 adolescents (ages 14.74 ± 1.92, 35 female), 40 with psychiatric symptoms and 13 healthy controls. At baseline, participants completed semi-structured diagnostic evaluations; dimensional assessments for anxiety, depression, anhedonia, and suicidality severity; and bloodwork to quantify CRP levels. Clinical assessments were repeated at longitudinal follow-up after approximately 1.5 years. Spearman’s correlation between CRP levels and follow-up symptom severity were controlled for BMI, age, sex, and follow-up interval and considered significant at the two-tailed, Bonferroni-adjustedp< 0.05 level.

Results

After correction for multiple comparisons, no relationships were identified between baseline CRP levels and follow-up symptom severity.

Conclusion

CRP levels were not significantly associated with future psychiatric symptoms in adolescents in this preliminary analysis. This may suggest that CRP is not a useful biomarker for adolescent depression and anxiety. However, future longitudinal studies with larger sample sizes and incorporating additional indicators of neuroinflammation are needed.
Modeling the dynamics of actin and myosin during bleb stabilization
Authors: Asante-Asamani Emmanuel , Dalton Mackenzie , Brazill Derrick , Strychalski Wanda
Published: October 2023

The actin cortex is very dynamic during migration of eukaryotes. In cells that use blebs as leading-edge protrusions, the cortex reforms beneath the cell membrane (bleb cortex) and completely disassembles at the site of bleb initiation. Remnants of the actin cortex at the site of bleb nucleation are referred to as the actin scar. We refer to the combined process of cortex reformation along with the degradation of the actin scar during bleb-based cell migration asbleb stabilization. The molecular factors that regulate the dynamic reorganization of the cortex are not fully understood. Myosin motor protein activity has been shown to be necessary for blebbing, with its major role associated with pressure generation to drive bleb expansion. Here, we examine the role of myosin in regulating cortex dynamics during bleb stabilization. Analysis of microscopy data from protein localization experiments inDictyostelium discoideumcells reveals a rapid formation of the bleb’s cortex with a delay in myosin accumulation. In the degrading actin scar, myosin is observed to accumulate before active degradation of the cortex begins. Through a combination of mathematical modeling and data fitting, we identify that myosin helps regulate the equilibrium concentration of actin in the bleb cortex during its reformation by increasing its dissasembly rate. Our modeling and analysis also suggests that cortex degradation is driven primarily by an exponential decrease in actin assembly rate rather than increased myosin activity. We attribute the decrease in actin assembly to the separation of the cell membrane from the cortex after bleb nucleation.
A Facile Method for Determining Lanthipeptide Stereochemistry
Authors: Luo Youran , Xu Shuyun , van der Donk Wilfred A.
Published: October 2023

Lanthipeptides are a large group of natural products that belong to the ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides contain lanthionine and methyllanthionine bis amino acids that have varying stereochemistry. The stereochemistry of new lanthipeptides is often not determined because current methods require equipment that is not standard in most laboratories. In this study, we developed a facile, efficient, and user-friendly method for detecting lanthipeptide stereochemistry utilizing advanced Marfey’s analysis. Under optimized conditions, 0.05 mg peptide is sufficient to characterize the stereochemistry of five (methyl)lanthionines of different stereochemistry using a simple liquid chromatography set-up, which is a much lower detection limit than current methods. In addition, we describe methods to readily access standards of the three different methyllanthionine stereoisomers and the two different lanthionine stereoisomers that have been reported in known lanthipeptides. The developed workflow uses commonly used non-chiral column system and offers a scalable platform to assist antimicrobial discovery. We illustrate its utility with an example of a lanthipeptide discovered by genome mining.
MET Inhibitor Capmatinib Radiosensitizes MET Exon 14-Mutated and MET-Amplified Non-Small Cell Lung Cancer
Authors: Ramesh Shrey , Cifci Ahmet , Javeri Saahil , Minne Rachel , Longhurst Colin A. , Nickel Kwangok P. , Kimple Randall J. , Baschnagel Andrew M.
Published: October 2023

Purpose

The objective of this study was to investigate the effects of inhibiting the MET receptor with capmatinib, a potent and clinically relevant ATP-competitive tyrosine kinase inhibitor, in combination with radiation in MET exon 14-mutated and MET-amplified non-small cell lung (NSCLC) cancer models.

Methods and Materials

In vitroeffects of capmatinib and radiation on cell proliferation, colony formation, MET signaling, apoptosis, and DNA damage repair were evaluated.In vivotumor responses were assessed in cell line xenograft and patient-derived xenograft models. Immunohistochemistry (IHC) was used to confirmin vitroresults.

Results

In vitroclonogenic survival assays demonstrated radiosensitization with capmatinib in both MET exon 14-mutated and MET-amplified NSCLC cell lines. No radiation-enhancing effect was observed in MET wild-type NSCLC and human bronchial epithelial cell line. Minimal apoptosis was detected with the combination of capmatinib and radiation. Capmatinib plus radiation compared to radiation alone resulted in inhibition of DNA double-strand break repair as measured by prolonged expression of γH2AX.In vivo, the combination of capmatinib and radiation significantly delayed tumor growth compared to vehicle control, capmatinib alone, or radiation alone. IHC indicated inhibition of phospho-MET and phospho-S6 and a decrease in Ki67 with inhibition of MET.

Conclusions

Inhibition of MET with capmatinib enhanced the effect of radiation in both MET exon 14-mutated and MET-amplified NSCLC models.
WITHDRAWN: Conformational Dynamics and Ligand Binding of the Human Voltage-Gated Proton Channel
Authors: Sun Xiaoyu , Mo Xue , Ruan Zhi , Chen Wen
Published: October 2023

Withdrawal Statement

The authors have withdrawn this manuscript because the backbone assignment needs recalibration. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Adaptive reuse of built heritage: conserving and designing with values
Authors: Augustiniok Nadin , Houbart Claudine , Plevoets Bie , Van Cleempoel Koenraad
Published: October 2023

Purpose

Adaptive reuse processes aim to preserve heritage values while creating new values through the architectural interventions that have become necessary. This claim provokes a discussion about the meaning of values, how we can preserve them in practice and how we can translate them into architectural qualities that users experience. Riegl's understanding of the different perspectives of heritage values in the past and present opens up the possibility of identifying present values as a reflection of current social, material and political conditions in the architectural discourse.

Design/methodology/approach

This qualitative and practical study compares two Belgian projects to trace the use of values in adaptive reuse projects from an architectural design perspective. The Predikherenklooster, a 17th-century monastery in Mechelen that now houses the public library, and the C-Mine cultural centre in Genk, a former 20th-century coal mine, are compared. The starting point is Flemish legislation, which defines significance through values, distinguishing between 13 heritage values.

Findings

The study demonstrates the opportunities that axiological questions offer during the design process of an adaptive reuse project. They provide an overarching framework for tangible and intangible aspects that need to be discussed, particularly in terms of the link between what exists, the design strategy and their effect.

Originality/value

Adaptive reuse can draw on approaches from both heritage conservation and contemporary architecture and explore values as a tool for “re-designing” built heritage.
Revisiting the financial development and economic growth nexus: empirical evidence from SAARC countries
Authors: Dar Muzffar Hussain , Nain Md Zulquar
Published: October 2023

Purpose

This study aims to examine the effect of economic growth and the moderating impact of inflation on financial development (FD) for six South Asian Association of Regional Countries (SAARC)es during the period of 1990–2020. Besides, the inflation threshold level and FD index are also estimated.

Design/methodology/approach

This study uses several cross-sectional dependency tests, pooled mean group and panel fully modified least squares method. This study also makes use of principle component analysis in index construction.

Findings

The results indicate that economic growth positively impacts regions’ FD. The mediating term has a negative impact on FD when the inflation rate rises. The finding indicates after the 3.5% threshold limit, inflation changes its positive effect on FD. The constructed index is a superior measurement of FD because it controls measurement sensitivity and offers significant results.

Originality/value

To the best of the authors’ knowledge, this is the first empirical study in the context of SAARC to analyse the interaction effect of inflation on the growth–finance relationship. This study’s novelty is further ensured by estimating the threshold level of inflation and construction index.
The effect of employee goal orientation on change-supportive behavior: a moderated mediation approach
Authors: Liu Mengli , Bai Minglei , Liu Bing , Li Yuhan
Published: October 2023

Purpose

Based on goal orientation theory, this study aims to examine how and when employees' performance goal orientations (PGOs) affect their change-supportive behavior in entrepreneurial firms undergoing change.

Design/methodology/approach

A two-wave time-lagged research design was applied to collect data from companies undergoing change in China.

Findings

The results showed that employees' performance-proving goal orientation (PPGO) was positively related to change-supportive behavior, and employees' performance-avoiding goal orientation (PAGO) was negatively related to change-supportive behavior. Openness to change played a mediating role in these mechanisms, and employees' learning goal orientation (LGO) played a moderating role.

Originality/value

By solving the mechanism of the relationship between PGOs and change-supportive behavior that has not been explored before, this study answers the question of how and when different PGOs affect support behavior.
Exploring teacher collaboration: what's inside the Malaysian PLC black box?
Authors: Mohd Zabidi Zuliana , Abdullah Zuraidah , Sumintono Bambang
Published: October 2023

Purpose

The purpose of this study is to explore mathematics teachers' collaboration within their professional learning communities (PLCs), and to gain insight into how the teachers developed their collective efficacy through it to focus on improving student learning.

Design/methodology/approach

Using a qualitative approach, data were collected from three high-performing secondary schools, mainly through semi-structured in-depth interviews with the Heads of Mathematics Unit. For explication and triangulation purposes, focus group interviews with the mathematics teachers and students and document analysis were also conducted.

Findings

The findings indicate that PLCs were the vessel through which a culture of disciplined teacher collaboration was fostered. More importantly, this culture encouraged teachers to participate in reflective dialogues that became a driver for their learning, and eventually led to their changed professional practice for improved student learning. The collaborative setting within the PLCs allowed teachers to pool their resources, knowledge and individual expertise to identify their student learning focus, and administer and measure their student intervention strategies. This collaborative professional learning reduced professional isolation, and as a result, improved teachers' collective pursuit of professional growth to impact student outcomes.

Research limitations/implications

The aim of this qualitative study was to provide a detailed description of the teachers' collaboration within their PLCs based on the researchers' interpretation of how the participants make sense of their PLC practices and experiences. Hence, findings are indicative, and not definitive. In addition, the Heads of the Mathematics Unit, and the mathematics teacher participants in this study illustrated salient aspects of subject subcultures, where their beliefs, norms and practices were non-generic, or specific only to their subject context. Therefore, the implications to practice were built from commonalities shared only among the mathematics units.

Originality/value

This is a study in a Malaysian context that provides empirical evidences that are concerned primarily with the process of teachers developing their collective efficacy through disciplined collaboration within their PLCs.
Insight into advances for the biosynthetic progress of fermented echinocandins of antifungals
Authors: Jiang Kaili , Luo Pan , Wang Xinxin , Lu Ling
Published: October 2023

Invasive fungal infections have increased remarkably, which have become unprecedented concern to human health. However, the effectiveness of current antifungal drugs is limited due to drug resistance and toxic side‐effects. It is urgently required to establish the effective biosynthetic strategy for developing novel and safe antifungal molecules economically. Echinocandins become a promising option as a mainstay family of antifungals, due to specifically targeting the fungal specific cell wall. To date, three kinds of echinocandins for caspofungin, anidulafungin, and micafungin, which derived from pneumocandin B0, echinocandin B, and FR901379, are commercially available in clinic and have shown potential in managing invasive fungal infections in a cost‐effective manner. However, current echinocandins‐derived precursors all are produced by environmental fungal isolates with long fermentation cycle and low yields, which challenge the production efficacy of these precursors in industry. Therefore, understanding their biosynthetic machinery is of great importance for improving antifungal titres and creating new echinocandins‐derived products. With the development of genome‐wide sequencing and establishment of gene‐editing technology, there are a growing number of reports on echinocandins‐derived products and their biosynthetic gene clusters. This review briefly summarizes the discovery and development history of echinocandins, compares their structural characteristics and biosynthetic processes, and sums up existed strategies for improving their production. Moreover, the genomic analysis of related biosynthetic gene clusters of echinocandins is discussed, highlighting the similarities and differences among the clusters. Last, the biosynthetic processes of echinocandins are compared, focusing on the activation and attachment of side‐chains and the formation of the hexapeptide core. This review aims to provide insights into the development and production of new echinocandin drugs by modifying the structure of echinocandin‐derived precursors and/or optimizing the fermentation processes; and achieve a new microbial chassis for efficient production of echinocandins in heterologous hosts.