bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical, Morphologic, and Molecular Spectrum of BRAF Fusion Spitz Tumors
Authors: Sharma Natasha , Patel Pragi , Chen Alice , Zhang Yongzhan , Fumero-Velázquez Mónica , Olivares Shantel , Nosek Daniel , Waldenbäck Pia , Kazakov Dmitry , Gerami Pedram
Published: August 2024

BRAF fusion Spitz neoplasms along with MAP3K8 fusions are among the subtypes of Spitz most likely to be diagnosed as Spitz melanoma. However, the current literature has only limited amounts of clinical follow-up on these cases. In this study, we share our experience with 39 BRAF fusion Spitz neoplasms and provide the greatest number of cases with available clinical follow-up. Among 24 patients with clinical follow-up (mean duration of 26.1 mo), none developed metastatic disease. Detailed biomarker assessment with FISH studies, TERT promoter mutational analysis, PRAME and p16 IHC also strongly favored a benign process. Only 2 of 17 cases were positive by FISH, 37 of 38 were negative for TERT promoter mutations, 24 of 24 were negative for PRAME and 16 of 21 had retained staining with p16. In addition, we identify and describe several distinct morphologic patterns, some of which are highly spitzoid in cytomorphology while others lack convincingly spitzoid cytomorphology. We address classification of those cases with less than classic spitzoid cytomorphology with a nonsupervised PCA plot which shows that independent of how spitzoid the cytomorphology is, BRAF fusions strongly cluster with other subtypes of Spitz neoplasms. In conclusion, we show with clinical follow-up, a meta-analysis of the current literature, and our biomarker analysis, that most BRAF fusion Spitz neoplasms have an indolent course and should be considered either benign or of intermediate grade. Further, our morphologic assessment and PCA plot suggest the morphologic spectrum of Spitz neoplasms may need to be expanded.
Are We Imaging Gently in Indiana? A System-Wide Population-Based Study of Chest CT Use in the Pediatric Trauma Population
Authors: Mannava Sindhu , Collings Amelia , Colgate Cameron , Timsina Lava , Landman Matthew
Published: August 2024

Objectives

Over the past decade, there has been a significant effort to decrease radiation exposure in pediatric trauma patients. The objective of this study was to determine if trauma centers (TCs) and nontrauma centers (non-TCs) are practicing in line with this effort. We hypothesized that TCs would demonstrate a significant decrease in the use of chest computed tomography (CT) during the study period, whereas non-TC would show no change in chest CT use.

Methods

We queried a state-wide database from 2010 to 2020 for pediatric trauma encounters at TCs and non-TCs within a single large health system. All transfer encounters were excluded. Chest CTs and chest radiographs (CXRs) were performed, and injury diagnosis codes were extracted for each encounter. Chest CT use and incidence of thoracic injuries were compared between TCs and non-TCs.

Results

A total of 13,014 encounters were included, of which 85.8% occurred at TCs and 14.2% occurred at non-TCs. There were significant differences between TC and non-TC encounter demographics. During the study period, the percentage of trauma encounters in which chest CT was obtained increased yearly at both TCs and non-TCs. Among encounters where both modalities were performed in the first 24 hours, chest CT was performed before CXR in 0.4% of TC and 0.1% of non-TC encounters (P = 0.086). Among encounters without thoracic injury, chest CT was performed in 5.2% of cases at non-TCs and 4.5% of cases at TCs (P < 0.001).

Conclusions

In the trauma encounters studied, chest CT was performed prior to CXR more frequently at TCs compared to non-TCs. These data may reflect regional trauma triage protocols, availability of chest CT, or differences in education between institutions. Whereas TCs may see more severely injured patients more frequently, education regarding conservative CT imaging principles should be reinforced through multidisciplinary efforts.
Serous Tubal Intraepithelial Carcinoma After Neoadjuvant Chemotherapy: A Report of 2 Cases
Authors: Stroot Iris A.S. , Smit Leonie , de Bock Geertruida H. , Wagner Marise M. , Jalving Mathilde , van Kempen Léon C.L.T. , Bart Joost , Mourits Marian J.E.
Published: August 2024

Serous tubal intraepithelial carcinoma (STIC) is regarded as the origin of most high-grade serous carcinomas (HGSC). After a diagnosis of isolated STIC, risk of developing HGSC is substantial. Since surveillance cannot detect HGSC in time to cure the disease, there is no consensus on the optimal treatment after a diagnosis of isolated STIC, but chemotherapy is considered one of the possible strategies. In this case report, we describe 2 women with advanced-stage HGSC treated with 3 cycles of neoadjuvant chemotherapy followed by interval debulking surgery. In both women, histopathological examination showed a complete histopathological tumor response, but a vital STIC was found in both cases. The 2 cases presented here indicate that STICs may not respond to chemotherapy. Further research focused on the underlying biology and chemosensitivity of STIC, as well as the effectiveness of treatment to prevent HGSC in case of isolated STIC, is needed.
Bridges to care: A collaborative, community-based model of rehabilitation in Dominican Republic using the World Health Organization’s framework of community engagement
Authors: Pullen Sara , Bretón Oscar , Damas Tiernan , Rodriguez Vargas Lucia
Published: August 2024

Background:

The most recent national population survey of the Dominican Republic (DR) estimated that ∼12.4% of all people in the country live with a disability. Ischemic heart disease is the number one cause of death in the DR, followed by stroke and road accidents, all of which, if survived, can cause significant suffering, disability, and need for rehabilitation.

Methods:

This study describes a sustainable, culturally responsive collaboration between the local health systems of the DR and the Rehabilitation Department of a U.S. medical school.

Results:

Over a period of 7 years, 855 patients were seen around 10 locations within a regional health area in teh DR. The majority of patients reported musculoskeletal pain, which reflects global health trends.

Conclusion:

The described collaborative work fosters a bidirectional partnership as well as enhanced rehabilitation access in a global context.
Reliability of a 2D-Panoramic Ultrasound System for the Determination of Muscle Volume in Older Hospitalized Patients
Authors: Boureau Anne Sophie , Anger Sylvain , Cornu Christophe , Mathieu Marie , Berrut Gilles , Nordez Antoine
Published: August 2024

Reliability of muscle thickness assessed in B-mode ultrasound has been confirmed in adults but remains a less direct assessment of muscle mass than muscle volume (MV). The aim of this prospective monocentric study was to assess the interday reliability of MV determined by the 2D-panoramic ultrasound in older hospitalized patients.

Ten participants hospitalized in geriatric ward (mean age = 84) underwent 2 sessions of panoramic ultrasound scanning 1 week apart for MV assessment and DXA for leg lean mass (LLM) assessment when it was possible. The interday reliability of MV assessed using the intraclass correlation coefficient (ICC) was excellent, whatever was the muscle analyzed: ICC = 0.99 for tibialis anterior; ICC = 0.99 for vastus lateralis; ICC = 1 for rectus femoris. The pilot analysis of its association with leg lean mass revealed a good association between the vastus lateralis MV and LLM, but this needs to be confirmed on a larger number of participants (Pearson correlation coefficient = 0.91, P = 0.03).

The 2D-panoramic ultrasound system for the determination of MV was reliable in older hospitalized patients with measurements performed on the patient's bed. MV seemed to be more correlated to LLM than muscle thickness. Future research will need to reduce the data processing time maybe with automation of data measurement.
Clinical Presentations and Surgical Outcomes in Traumatic Iris and Lens-Related Injuries Due to Blunt Trauma
Authors: Özer Ömer , Güçlü Emin S.
Published: August 2024

Purpose:

The aim of this study was to evaluate the clinical presentation, treatment options, and surgical outcomes of patients admitted with traumatic iris and lens-related injuries due to blunt trauma.

Methods:

This retrospective study included 43 eyes of 43 patients who presented with traumatic iris and lens injuries between September 01, 2022 and July 01, 2023.

Results:

The mean age was 46.1±14.6 years and the mean ocular trauma score was 74.7±9.9. According to the cause of injury, the most common cause in males is assault, and the most common cause in females is fall. Nine (20.9%) patients underwent pars plana vitrectomy. Six (14%) patients underwent cataract surgery with phacoemulsification and intraocular lens implantation into “the bag.”

Conclusions:

In conclusion, other concomitant pathologies may make these surgeries difficult to perform. Early evaluation and timely management are essential to achieve the best possible outcomes in patients with traumatic iris and lens-related injuries.
Effect of Nasal Septoplasty on Fibrinogen/HDL Ratio in Patients With Nasal Septal Deviation
Authors: Bayram Ali , Şahin Mustafa , Alici Sert Gökçen
Published: August 2024

Objective:

The present study aimed to investigate the plasma fibrinogen/high-density lipoprotein (HDL) ratio in patients with marked nasal septal deviation (NSD) and to evaluate the effect of septoplasty on this ratio.

Methods:

The present prospective study included 56 patients who had a septoplasty due to a marked NSD (NSD group) in an academic tertiary hospital and 40 age-matched and sex-matched healthy volunteers (control group) between April 2019 and December 2021. The diagnosis of marked NSD was performed via a detailed otorhinolaryngological examination, nasal endoscopy, and computed tomography finding. All patients in the NSD group were evaluated for plasma fibrinogen, HDL, mean platelet volume (MPV), platelet distribution width (PDW), and fibrinogen/HDL values before and 3 months after surgery, and preoperative values were compared with the control group. Preoperative and postoperative fibrinogen, HDL, MPV, PDW, and fibrinogen/HDL values were also compared in the NSD group.

Results:

There was no significant difference between the NSD and control groups regarding age, sex, fibrinogen, HDL, MPV, PDW, and fibrinogen/HDL values. Fibrinogen, MPV, and fibrinogen/HDL values were significantly decreased, whereas HDL levels significantly increased after septoplasty in the NSD group. There was no significant difference in terms of preoperative and postoperative PDW values.

Conclusion:

To the best of our knowledge, this is the first study investigating the fibrinogen/HDL ratio and the effect of septoplasty on this ratio in NSD in the literature. In the present study, the fibrinogen/HDL ratio was significantly decreased after septoplasty in patients with NSD, which may be attributed to the therapeutic effect of nasal septoplasty on the restoration of hypercoagulopathy provoked by chronic hypoxia.
Preoperative CT Measurements and Computer-assisted Design in Auricular Reconstruction for Microtia
Authors: Qian Jin , He Bei , Lu Peng , Liu Tun
Published: August 2024

Objective:

To evaluate the utility of 3-dimensional computed tomography (3D CT) reconstruction in rib cartilages harvest and auricular reconstruction.

Methods:

This was a retrospective study of 105 patients with microtia who underwent auricular reconstruction in our department, including 53 controls. All patients underwent chest CT scans and 52 patients in the CT group underwent rib cartilage reconstruction simultaneously. All patients’ sex, age, height, and body weight were reviewed. Preoperative CT measurements included the length and width of the sixth, seventh, eighth, and ninth rib cartilages. Operative measurements included the number, amount, length and width of the costal cartilages harvested, operation time, and the amount of bleeding.

Results:

There was no significant difference in the preoperative and operative measurements of the seventh rib. The mean age, height, and weight of the 3D CT group were significantly less than the control group. Compared with the control group, the costicartilage taken in the 3D CT group was significantly shorter in length, but there was no significant difference in the number of ribs taken. The operation time of the 3D CT group was less than the control group.

Conclusions:

Reconstructive 3D CT provides vivid and accurate data of costochondral volume, and is valuable for surgical timing and cartilage sculpting. With the aid of the 3D CT measurements, surgeons can make an individualized surgical planning. Unnecessary harvest of rib cartilage and surgical time are avoided by having a throughout plan before operation.
Efficacy and Safety of Minimally Invasive Neuroendoscopic Surgery in the Therapy of Supratentorial Hypertensive Intracerebral Hemorrhage: A Meta-Analysis
Authors: Ren Wenbo , Wang Wei , Wang Liang , Liu Xiaozhi , Zhao Yujun
Published: August 2024

Objective:

To systematically investigate the therapeutic effects of neuroendoscopic (NE) surgery in supratentorial hypertensive intracerebral hemorrhage (HICH), including key indicators such as hematoma evacuation rate, complications, and neurological prognosis, thus comprehensively understanding the superiority of NE surgery in supratentorial HICH therapy, and to provide scientific basis and decision-making support for clinical practice.

Methods:

The PubMed, EMBASE, Cochrane, Google, and CNKI databases were searched for relevant literature related to NE surgery for supratentorial HICH published before October 2023. Summary analyses of hematoma evacuation rate, mortality, clinical treatment, good functional outcome (Glasgow Outcome Scale, Glasgow Coma Scale, and modified Rankin Scale), and postoperative complications in the NE group were performed, and Revman 5.3 was used to conduct the meta-analysis.

Results:

Fourteen trials with 1266 patients were enrolled in this meta-analysis, with an overall moderate risk of bias. Compared with craniotomy, NE-treated patients had a higher rate of cerebral hematoma evacuation, and their operative time, intraoperative blood loss, and hospital stay were markedly reduced. Moreover, NE surgery could better restore patients’ neurological function and autonomy, presenting a higher Glasgow Outcome Scale, Glasgow Coma Scale, and a lower modified Rankin Scale. Moreover, NE surgery effectively reduced the incidence of mortality and postoperative complications, especially rebleeding and lung infection.

Conclusion:

Neuroendoscopic surgery not only better removes intracranial hematomas and improves neurological function and autonomy in supratentorial HICH patients, but also effectively reduces mortality and postoperative complications.
Using a Zipper Device to Minimize Scarring After Excision of Facial Nevi in Pediatric Patients
Authors: Huang Chong , Liu Ou-Gen
Published: August 2024

Background:

This study aims to investigate the safety and effectiveness of using a zipper device to minimize scarring after facial nevi excision in pediatric patients.

Methods:

A total of 48 patients were included, with 23 in the control group and 25 in the zipper group. The zipper device was used immediately to equalize skin tension after facial nevi excision. The primary outcome was the scar width measured at 1, 3, 6, and 12 months postoperatively. The Vancouver Scar Scale (VSS) was used to assess patients’ scars at postoperative 12 months as a secondary outcome.

Results:

Two patients in the zipper group withdrew from the trial due to skin irritation. The symptom disappeared within a week after the zipper device was removed. The scar width in the zipper group was smaller than that in the control group at postoperative 1, 3, 6, and 12 months. In addition, the VSS scores for scarring also showed that patients in the zipper group had significantly better scar scores than those in the control group. At postoperative 6 months, scar morphology was essentially similar to that at post 12 months in both groups, and there was a significant positive correlation between scar morphology at the 2 time points,

Conclusion:

It is safe and effective to use this zipper device to minimize scarring after excision of facial nevi in pediatric patients, and we think it be a complementary therapeutic measure in pediatric patients after facial nevus excision.

Level of Evidence:

II.
Interruption reduction during oral medication rounds among nurses in hematology-oncology wards: a best practice implementation project
Authors: Siah Jia Wen , Cheng Crystal Kai Tian , Choy Chloe Leyi , Tho Poh Chi , Lang Siew Ping
Published: August 2024

Objectives:

The aim of the project was to reduce interruptions during oral medication rounds among nurses working in hematology-oncology wards by improving compliance with best practices by 20%.

Introduction:

Medication errors can adversely affect patient safety. Hence, understanding the underlying contributors to medication errors is necessary. Nurses are the ones who administer medications to patients; however, in clinical areas, interruptions are prevalent and could contribute to medication errors. It is therefore recommended that interventions be implemented to minimize interruptions.

Methods:

This project was conducted in two hematology-oncology wards from March 2022 to March 2023. Target participants were nurses who served medications in the morning. The project followed an evidence-based audit and feedback methodology using the seven-phase JBI Evidence Implementation Framework. JBI's Practical Application of Clinical Evidence System (PACES) was used to support the audit and feedback process. An interruption reduction bundle consisting of three best practices was implemented.

Results:

At baseline, only 24% of medications administered occurred without interruption. One month after implementation, there was a 51% improvement in compliance. Six months after implementation, compliance increased to 58%. Nine months post-implementation, the compliance rate remained at 59%. Absolute interruption counts decreased from 47 (baseline), to 27 (1 month post-implementation), to 24 (6 months post-implementation), to 16 (9 months post-implementation). All types of interruptions decreased when comparing the baseline with the latest post-implementation result.

Conclusions:

The project used evidence-based interventions in a bundle, effectively reducing interruptions during oral medication rounds, and sustaining positive results.

Spanish abstract:

http://links.lww.com/IJEBH/A256
An autosomal dominant cardiac arrhythmia syndrome, ST Depression Syndrome, is caused by thede novocreation of a cardiomyocyte enhancer
Authors: de Villiers Carin P. , Downes Damien J. , Goel Anuj , Pagnamenta Alistair T. , Ormondroyd Elizabeth , Sparrow Alexander J. , Nornes Svanhild , Giacopuzzi Edoardo , Rath Phalguni , Davies Ben , Schwessinger Ron , Gosden Matthew E. , Beagrie Robert A. , Parkes Duncan , Hastings Rob , Lise Stefano , Salatino Silvia , Roberts Hannah , Lopopolo Maria , Weldon Carika , Trebes Amy ,   The WGS500 consortium, Buck David , Taylor Jenny C. , Redwood Charles , Rowland Edward , Tharmaratnam Dushen , Stuart Graham , Lambiase Pier D. , De Val Sarah , Hughes Jim R. , Watkins Hugh
Published: August 2024

A substantial proportion of mutations underlying rare Mendelian diseases remain unknown, potentially because they lie in the non-coding genome. Here, we report the mapping of the causal mutation of an autosomal dominant cardiac arrhythmia syndrome, ST Depression Syndrome, which is associated with widespread ST-depression on the electrocardiogram together with risk of sudden death and heart failure, to the non-coding region of theKCNB1locus. Using genetic linkage analysis, we narrowed the associated region to 1cM of the genome and then with a genome editing approach, we show that the mutation, a small complex insertion-deletion, generates ade novogain-of-function enhancer that drives higher expression ofKCNB1in cardiomyocytes. This is the first report of a gain ofde novoenhancer function causing Mendelian disease. Critically, the tissue-specific gain-of-function regulatory change could be predicted using a deep neural network. Application of a similar framework will enable identification of causal non-coding mutations and affected genes in other rare diseases.
Prevalence of Body-focused repetitive behaviours among undergraduate medical students at public sector university karachi
Authors: Tunio Marium Munir , Eshika  , Devi Vandna , JaiRam  , Kirshna  , Sandesh  , Kumari Vandna , Jamshaid
Published: August 2024

Background

Body-focused repetitive behaviors (BFRBs) is a catch-all term for a group of obsessive behaviors, including skin picking (dermatillomania), hair pulling (trichotillomania), nail-biting (onychophagia), and nose picking (rhinotillexomania), which have a negative impact on both physical and mental health. The aim of this study was to assess the prevalence of BFRBs among medical students aged 18 to 25 attending Jinnah Sindh Medical University Karachi.

Methodology

A cross-sectional study was conducted on 295 medical students of Jinnah Sindh Medical University Karachi. Data was collected through an online questionnaire which consisted of socio-demographic characteristics, engagement in BFRBs and distress due to it.

Results

Majority of participants (61.2%) were in their clinical years (3rd, 4th and 5th). Among those exhibiting BFRBs, 69.9% were female. Through this study we found that the most common BFRB among the medical students of Jinnah Sindh Medical University is Nail biting which is 22.8% followed by Skin picking disorder which is 19.1%,Hair pulling 17.1%,Cheek biting 13.8% followed by Nose picking 7.7%

Conclusion

In our research, it has been noticed that participants were engaged in BFRBs. But it was not significantly common in adults. Majority of respondents reported never engaging in these behaviors (skin picking, hair pulling, nail-biting, nose picking and cheek biting). While a significant percentage of respondents engaged occasionally or frequently in these behaviors.
Single-cell RNA Sequencing of Peripheral Blood Mononuclear Cells in Patients with Single Ventricle/Hypoplastic Left Heart Syndrome
Authors: Qu Hui-Qi , Ostberg Kayleigh , Slater Diana J , Wang Fengxiang , Snyder James , Hou Cuiping , Connolly John J , March Michael , Glessner Joseph T , Kao Charlly , Hakonarson Hakon
Published: August 2024

Background

Single ventricle and hypoplastic left heart syndrome (SV/HLHS) patients require lifelong medical monitoring and management to address potential complications and optimize their health. The consequence of SV/HLHS had detrimental effects on multiple organ systems, including on peripheral blood mononuclear cells (PBMCs) and can weaken the immune system, exacerbating the risk of infection and various cardiovascular complications.

Methods

Using single-cell RNA sequencing (scRNA-seq), we studied PBMCs from 33 pediatric patients (10 females and 23 males) with SV/HLHS. By a pair-wide study design, the SV/HLHS patients were compared to 33 controls without heart diseases.

Results

Four cell types account for the top 62% cumulative importance of disease effects on gene expression in different cell types, i.e., [T cells, CD4+, Th1/17], [T cells, CD4+, TFH], [NK cells], and [T cells, CD4+, Th2]. Significant sex differences were observed in [T cells, CD4+, TFH], with less prominent effects in female patients. A total of 6659 genes in different cell types were significantly differentially expressed (DE). Hierarchical clustering by WGCNA analysis of the DE genes revealed that DE genes in NK cells are most closely related to those in SV/HLHS. A total of 822 genes showed cell specific DE with opposite directions in different cell types, highlighting overrepresented MYC and IFN-γ activity in T cell and NK cell populations, as well as underrepresentation in monocytes and Treg cells.

Conclusion

This study elucidates the complex transcriptome landscape in PBMCs in patients with SV/HLHS, emphasizing the differential impacts on various cell types. New insights are gained into the precise modulation of MYC and IFN-γ activity in SV/HLHS, which may help balance immune responses and reduce harmful inflammation, and promote effective tissue repair and infection control.
Detection of protein-protein interactions by bio-orthogonal fluorogenic proximity probes
Authors: Torell Andreas , Larsson N. Alfred , Phillipson Storm , Odell Luke R. , Fürth Daniel
Published: August 2024

Detecting protein-protein interactions within cells is challenging. Transgenic approaches risk altering protein function via fluorescent tagging, whilein situmethods lackin vivocompatibility. Here, we introduce fluorogenic probes with dual-tetrazine pegylated branched arms linked to xanthene dye. Activation requires both tetrazine arms to interact simultaneously with target proteins, enabling dual-substrate recognition. We applied our method to detect protein-protein interactions in both fixed and living cells, utilizing antibody conjugation for fixed cells and genetic code expansion for real-time detection in living cells. Our strategy ensures versatile applicability and seamless transition between fixed and living systems.
Re-programming of GM-CSF-dependent alveolar macrophages through GSK3 activity modulation
Authors: Ríos Israel , Herrero Cristina , Torres-Torresano Mónica , López-Navarro Baltasar , Schiaffino María Teresa , Díaz-Crespo Francisco , Nieto-Valle Alicia , Samaniego Rafael , Sierra-Palomares Yolanda , Oliver Eduardo , Revuelta-Salgado Fernando , García-Luján Ricardo , Sánchez-Mateos Paloma , Delgado Rafael , Puig-Kröger Amaya , Corbí Ángel L.
Published: August 2024

Monocyte-derived macrophages recruited into inflamed tissues can acquire an array of functional states depending on the extracellular environment. Since the anti-inflammatory/pro-fibrotic macrophage profile is determined by MAFB, whose activity/protein levels are regulated by GSK3, we addressed the macrophage re-programming potential of GSK3 modulation. GM-CSF-dependent (GM-MØ) and M-CSF-dependent monocyte-derived macrophages (M-MØ) exhibited distinct levels of inactive GSK3, and inhibiting GSK3 in GM-MØ led to acquisition of transcriptional, phenotypic and functional properties characteristic of M-MØ (enhanced expression of IL-10 and monocyte-recruiting factors, and higher efferocytosis). These re-programming effects were also observed upon GSK3α/β knockdown, and through GSK3 inhibition inex vivoisolated human alveolar macrophages (AMØ). Notably, GSK3 downmodulation potentiated the transcriptional signature of Interstitial Macrophages (IMØ) while suppressed the AMØ-specific gene profile. Indeed, heightened levels of inactive GSK3 and MAFB-dependent proteins were observed in severe COVID-19 patients lung macrophages, highlighting the GSK3-MAFB axis as a therapeutic target for macrophage re-programming.
TRACKING CLONAL AND PLASMID TRANSMISSION IN COLISTIN AND CARBAPENEM RESISTANTKLEBSIELLA PNEUMONIAE
Authors: Akintayo Ifeoluwa , Siroglavic Marko , Frolova Daria , Silva Mabel Budia , Grundmann Hajo , Iqbal Zamin , Budimir Ana , Reuter Sandra
Published: August 2024

The surveillance of mobile genetic elements facilitating the spread of antimicrobial resistance genes has been challenging. Here, we tracked both clonal and plasmid transmission in colistin- and carbapenem-resistantK. pneumoniaeusing short and long read sequencing technologies. We observed three clonal transmissions, all containing IncL plasmids andblaNDM−1, although not co-located on the same plasmid. One IncL-blaNDM−1plasmid had been transferred between ST392 and ST15, and the promiscuous IncL-blaOXA−48plasmid was likely shared between a singleton and a clonal transmission of ST392. Plasmids within clonal outbreaks and between clusters and STs had 0-2 SNP differences, showing high stability upon transfer to same or different STs. The simplest explanation of a single common IncL-blaNDM−1plasmid spreading was in fact false, and we foundblaNDM−1in the context of five different plasmids, emphasizing the need to investigate plasmid-mediated transmission for effective containment of outbreaks.

IMPORTANCE

Antimicrobial resistance occupies a central stage in global public health emergencies. Recently, efforts to track the genetic elements that facilitate the spread of resistance genes to determine so-called plasmid outbreaks have been described, however, such short read sequencing hinders full knowledge about plasmid structure and makes this approach very challenging to implement. In this study we used both short and long read sequencing in clinical Klebsiella pneumoniae from University Hospital Centre Zagreb, Croatia which were resistant to both last resort antibiotics colistin and carbapenem. Our results show complex transmission networks and sharing of plasmids, emphasizing multiple transmissions of plasmids harbouring carbapenem and/or colistin resistance genes between and within K. pneumoniae clones. Only full length sequencing plus a novel way of determining plasmid clusters resulted in the full picture, showing how future active monitoring of plasmids as a vital tool for infection prevention and control could be implemented.
Genomic sequence analysis of the first mpox virus detected in Kenya
Authors: Langat Solomon K. , Limbaso Konongoi , Khamadi Samoel , Nyunja Albert , Pilarowski Genay , Okunga Emmanuel , Ofula Victor , Oluniyi Paul , Koka Hellen , Koskei Edith , Owaka Samuel , Chelangat Betty , Mulwa Francis , Mutisya James , Chepkorir Edith , Lutomiah Joel , Langat Daniel , Amoth Patrick , Songok Elijah
Published: August 2024

Mpox is a zoonotic disease caused by the Monkeypox virus (MPXV) in the family: Poxviridae, genus: Orthopoxvirus. Historically, the disease was restricted mostly to Africa with cases being reported in Central Africa (mostly caused by clade I) and in West Africa (caused by clade II). However, there has been a recent shift in the virus range with outbreaks being reported in Europe and America, and in countries where the virus was initially not endemic. This multi-country outbreak was driven mostly by clade IIb lineage of MPXV. Since December 2023, there has been an ongoing mpox outbreak in the Democratic Republic of Congo (DRC), driven by a new clade I lineage of the virus, designated clade Ib. The DRC outbreak has persisted, with an increase in cases being reported over the past few months. Spillover of these outbreak-related cases to the neighbouring countries have also been reported in multiple countries including Uganda and Rwanda. Here, we report the rapid application of unbiased metagenomic next generation sequencing (mNGS) to reconstruct the genome sequence of the first reported case of MPXV in Kenya. Our findings show that the Kenyan case clusters together with clade Ib MPXV strains, associated with the sustained outbreak in the DRC. Clade Ib lineage has been associated with continuing geographical expansion of the virus to previously unaffected areas, high incidence of the disease as well as high case fatality (CFR 4.9-6.7%). Similar to other clade Ib strains, the Kenyan strain carries predominant APOBEC3-type mutations which is characteristic feature of human-to-human transmission, highlighting the need for surveillance to curtail any potential expansion of this MPXV strain. The lack of information on genomes associated with cases reported in different East African countries, is a gap that urgently needs to be addressed to aid in the monitoring of this MPXV strain. This case investigation, therefore, underscores the need for sequencing efforts to be enhanced across the continent to help improve our understanding of the geographical range and diversity of the MPXV strains, especially those belonging to clade I which is currently under-represented.
Replicating the Association of Variants inBSNandAPBA1with Obesity in Diverse Populations
Authors: Robinson Jamie R. , Denny Joshua C. , Zeng Chenjie
Published: August 2024

In a recent study by Zhao et al., rare protein-truncating variants (PTVs) in the BSN and APBA1 genes showed effects on obesity that exceeded those of well-known genes such as MC4R in a UK cohort. In this study, we leveraged the All of Us Research Program, to investigate the association of predicted LoF (pLoF) PTVs in BSN and APBA1 with body mass index (BMI) across a population of diverse ancestry. Our analysis revealed that the impact of pLoF variants in BSN and APBA1 on BMI was notably greater in this cohort, especially among individuals of European ancestry. Additionally, a phenome-wide association study (PheWAS) using the extensive phenotypic data available in the All of Us Research Program uncovered novel associations ofBSNandAPBA1heterozygous pLoF carriers with various phenotypes. Specifically, BSN pLoF variants were associated with pulmonary hypertension, atrial fibrillation, and anticoagulant use, while APBA1 pLoF variants were linked to disorders of the temporomandibular joint. These findings underscore the potential of large-scale biobanks in advancing genetic discovery.
Serum interferon-gamma-induced protein 10 levels can help predict sarcopenia development in patients with primary hepatocellular carcinoma: A retrospective cohort study
Authors: Takada Hitomi , Osawa Leona , Komiyama Yasuyuki , Muraoka Masaru , Suzuki Yuichiro , Sato Mitsuaki , Kobayashi Shoji , Yoshida Takashi , Takano Shinichi , Maekawa Shinya , Enomoto Nobuyuki
Published: August 2024

Background Sarcopenia is a prognostic factor in patients with hepatocellular carcinoma (HCC). However, the mechanism underlying sarcopenia development in these patients remains unclear. The chemokine interferon-gamma-induced protein 10/C-X-C motif chemokine ligand 10 (IP-10) has been found to be associated with muscle regeneration or destruction. Thus, we aimed to clarify the role of serum IP-10 levels in predicting sarcopenia development in patients with HCC. Methods This retrospective study enrolled 120 patients with primary HCC whose serum IP-10 levels were measured both at baseline and 1 year after the confirmed diagnosis of HCC. Patients who had sarcopenia at baseline computed tomography imaging were assigned to the Sarco-base group, whereas those in whom sarcopenia was found for the first time during the 3-year follow-up were assigned to the Sarco-develop group. Those who never met the criteria during the follow-up period were assigned to the Non-Sarco group. Results The baseline IP-10 levels were significantly lower in the Sarco-base group compared to the rest (88 vs. 110 pg/ml, p = 0.016). Conversely IP-10 levels and IP-10 ratio at 1 year after the confirmed diagnosis of HCC were lower in the Non-Sarco group compared to the rest (25 vs. 62 pg/ml, p < 0.001, 0.91 vs. 1.1, p = 0.044). Further comparisons between the three groups show that the baseline IP-10 levels were higher in the Sarco-develop group than in the Sarco-base (p < 0.001) and Non-Sarco (p = 0.0017) groups. Conclusions Patients with sarcopenia at baseline more frequently presented with low IP-10 levels than those without. Contrarily, the group without sarcopenia at baseline and with high baseline IP-10 levels and IP-10 ratios at 1 year were more likely to develop sarcopenia within 3 years. Monitoring of IP-10 levels may enable the identification of groups prone to develop sarcopenia in patients with HCC.
Application of the J-CTO Score to Intraplaque Guidewire Tracking-Based Recanalization for In-Stent Chronic Total Occlusions
Authors: Chen Chieh-Yu , Huang Chi-Hung , Cheng Jen-Fang , Lee Chien-Lin , Chiang Jiun-Yang , Liu Shih-Chi , Chang Chi-Jen , Lin Chia-Pin , Tsai Cheng-Ting , Liou Jun-Ting , Tsai Chia-Ti , Wang Yi-Chih , Hwang Juey-Jen
Published: August 2024

Background

The application of the J-CTO score for in-stent chronic total occlusion (CTO) recanalization remains unclear. We aimed to compare the role of J-CTO score in in-stent and de novo CTO interventions using intraplaque guidewire tracking techniques.

Methods

The application of the J-CTO score to assess procedural feasibility and guidewire crossing time for in-stent (N=74, 14.6%) and de novo CTO (N=434, 85.4%) interventions was evaluated in consecutive 508 patients (64.1±11.6 years, 446 men). Failed intraplaque tracking (N=3) or guidewires crossing (N=35) was considered procedural failures (38/508=7.5%).

Results

The procedural success rate for de novo CTOs significantly declined when the J-CTO score was >2 (85 vs. ≤2: 97%, p<0.001), but was comparable for in-stent CTOs (>2: 96 vs. ≤2: 100%, p=0.400). Among 470 patients with successful recanalization, the guidewire crossing time ≥30 minutes was required less for in-stent than for de novo CTOs (OR=0.40, 95% CI=0.18-0.86) with J-CTO score ≥2 in multivariate analysis. For those with successful antegrade-only wiring, the guidewire crossing time shown by Kaplan–Meier curves was significantly related to the J-CTO score for either in-stent (N=72) or de novo (N=370) CTOs (both p<0.001 by log-rank test). However, only blunt stump (15.0±5.6 min) and occlusion ≥20mm (16.2±5.6 min) were independent time-determining factors of guidewire crossing (both p<0.01) for in-stent CTOs.

Conclusion

With the intraplaque tracking strategy, the effects of the J-CTO score on procedural feasibility and guidewire crossing time differ for in-stent and de novo CTOs. Therefore, the J-CTO score should be cautiously interpreted during in-stent CTO interventions.
Predicting mortality in critically ill patients with hypertension using machine learning and deep learning models
Authors: Zhang Ziyang , Ye Jiancheng
Published: August 2024

Background

Accurate prediction of mortality in critically ill patients with hypertension admitted to the Intensive Care Unit (ICU) is essential for guiding clinical decision-making and improving patient outcomes. Traditional prognostic tools often fall short in capturing the complex interactions between clinical variables in this high-risk population. Recent advances in machine learning (ML) and deep learning (DL) offer the potential for developing more sophisticated and accurate predictive models.

Objective

This study aims to evaluate the performance of various ML and DL models in predicting mortality among critically ill patients with hypertension, with a particular focus on identifying key clinical predictors and assessing the comparative effectiveness of these models.

Methods

We conducted a retrospective analysis of 30,096 critically ill patients with hypertension admitted to the ICU. Various ML models, including logistic regression, decision trees, and support vector machines, were compared with advanced DL models, including 1D convolutional neural networks (CNNs) and long short-term memory (LSTM) networks. Model performance was evaluated using area under the receiver operating characteristic curve (AUC) and other performance metrics. SHapley Additive exPlanations (SHAP) values were used to interpret model outputs and identify key predictors of mortality.

Results

The 1D CNN model with an initial selection of predictors achieved the highest AUC (0.7744), outperforming both traditional ML models and other DL models. Key clinical predictors of mortality identified across models included the APS-III score, age, and length of ICU stay. The SHAP analysis revealed that these predictors had a substantial influence on model predictions, underscoring their importance in assessing mortality risk in this patient population.

Conclusion

Deep learning models, particularly the 1D CNN, demonstrated superior predictive accuracy compared to traditional ML models in predicting mortality among critically ill patients with hypertension. The integration of these models into clinical workflows could enhance the early identification of high-risk patients, enabling more targeted interventions and improving patient outcomes. Future research should focus on the prospective validation of these models and the ethical considerations associated with their implementation in clinical practice.
Development of an optimized machine learning approach for assessing brain metastatic burden in preclinical models
Authors: Rappaport Jessica , Chen Quanyi , McGuire Tomi , Daugherty-Lopès Amélie , Goldszmid Romina
Published: August 2024

Brain metastases (BrM) occur when malignant cells spread from a primary tumor located in other parts of the body to the brain. BrM is a deadly complication for cancer patients and currently lacks effective therapies. Due to the limited access to patient samples, preclinical models remain a valuable tool for studying metastasis development, progression, and response to therapy. Thus, reliable methods for quantifying metastatic burden in these models are crucial. Here, we describe step by step a new semi-automatic machine-learning approach to quantify metastatic burden on mouse whole-brain stereomicroscope images while preserving tissue integrity. This protocol utilizes the open-source, user-friendly image analysis software QuPath. The method is fast, reproducible, unbiased, and provides access to data points not always obtainable with other existing strategies.
Speech Synthesis from Electrocorticogram During Imagined Speech Using a Transformer-Based Decoder and Pretrained Vocoder
Authors: Komeiji Shuji , Shigemi Kai , Mitsuhashi Takumi , Iimura Yasushi , Suzuki Hiroharu , Sugano Hidenori , Shinoda Koichi , Yatabe Kohei , Tanaka Toshihisa
Published: August 2024

This study describes speech synthesis from an Electrocorticogram (ECoG) during imagined speech. We aim to generate high-quality audio despite the limitations of available training data by employing a Transformer-based decoder and a pretrained vocoder. Specifically, we used a pre-trained neural vocoder, Parallel WaveGAN, to convert the log-mel spectrograms output by the Transformer decoder, which was trained on ECoG signals, into high-quality audio signals. In our experiments, using ECoG signals recorded from 13 participants, the synthesized speech from imagined speech achieved a dynamic time-warping (DTW) Pearson correlation ranging from 0.85 to 0.95. This high-quality speech synthesis can be attributed to the Transformer decoder’s ability to accurately reconstruct high-fidelity log-mel spectrograms, demonstrating its effectiveness in dealing with limited training data.
Tracking clonal evolution of drug resistance in ovarian cancer patients by exploiting structural variants in cfDNA
Authors: Williams Marc J. , Vázquez-García Ignacio , Tam Grittney , Wu Michelle , Varice Nancy , Havasov Eliyahu , Shi Hongyu , Satas Gryte , Lees Hannah J. , Lee Jake June-Koo , Myers Matthew A. , Zatzman Matthew , Rusk Nicole , Ali Emily , Shah Ronak H , Berger Michael F. , Mohibullah Neeman , Lakhman Yulia , Chi Dennis S. , Abu-Rustum Nadeem R. , Aghajanian Carol , McPherson Andrew , Zamarin Dmitriy , Loomis Brian , Weigelt Britta , Friedman Claire F. , Shah Sohrab P.
Published: August 2024

Drug resistance is the major cause of therapeutic failure in high-grade serous ovarian cancer (HGSOC). Yet, the mechanisms by which tumors evolve to drug resistant states remains largely unknown. To address this, we aimed to exploit clone-specific genomic structural variations by combining scaled single-cell whole genome sequencing with longitudinally collected cell-free DNA (cfDNA), enabling clonal tracking before, during and after treatment. We developed a cfDNA hybrid capture, deep sequencing approach based on leveraging clone-specific structural variants as endogenous barcodes, with orders of magnitude lower error rates than single nucleotide variants in ctDNA (circulating tumor DNA) detection, demonstrated on 19 patients at baseline. We then applied this to monitor and model clonal evolution over several years in ten HGSOC patients treated with systemic therapy from diagnosis through recurrence. We found drug resistance to be polyclonal in most cases, but frequently dominated by a single high-fitness and expanding clone, reducing clonal diversity in the relapsed disease state in most patients. Drug-resistant clones frequently displayed notable genomic features, including high-level amplifications of oncogenes such asCCNE1,RAB25,NOTCH3, andERBB2. Using a population genetics Wright-Fisher model, we found evolutionary trajectories of these features were consistent with drug-induced positive selection. In select cases, these alterations impacted selection of secondary lines of therapy with positive patient outcomes. For cases with matched single-cell RNA sequencing data, pre-existing and genomically encoded phenotypic states such as upregulation of EMT and VEGF were linked to drug resistance. Together, our findings indicate that drug resistant states in HGSOC pre-exist at diagnosis and lead to dramatic clonal expansions that alter clonal composition at the time of relapse. We suggest that combining tumor single cell sequencing with cfDNA enables clonal tracking in patients and harbors potential for evolution-informed adaptive treatment decisions.
Leveraging Generative AI to Accelerate Biocuration of Medical Actions for Rare Disease
Authors: Niyonkuru Enock , Caufield J Harry , carmody Leigh , Gargano Michael , Toro Sabrina , Whetzel Trish , Blau Hannah , Soto Mauricio , Casiraghi Elena , Chimirri Leonardo , Reese Justin T , Valentini Giorgio , Haendel Melissa A , Mungall Christopher J , Robinson Peter N.
Published: August 2024

Background: Structured representations of clinical data can support computational analysis of individuals and cohorts, and ontologies representing disease entities and phenotypic abnormalities are now commonly used for translational research. The Medical Action Ontology (MAxO) provides a computational representation of treatments and other actions taken for the clinical management of patients. Currently, manual biocuration is used to assign MAxO terms to rare diseases, enabling clinical management of rare diseases to be described computationally for use in clinical decision support and mechanism discovery. However, it is challenging to scale manual curation to comprehensively capture information about medical actions for the more than 10,000 rare diseases. Methods: We present AutoMAxO, a semi-automated workflow that leverages Large Language Models (LLMs) to streamline MAxO biocuration for rare diseases. AutoMAxO first uses LLMs to retrieve candidate curations from abstracts of relevant publications. Next, the candidate curations are matched to ontology terms from MAxO, Human Phenotype Ontology (HPO), and MONDO disease ontology via a combination of LLMs and post-processing techniques. Finally, the matched terms are presented in a structured form to a human curator for approval. Results: We used this approach to process 4,918 unique medical abstracts and identified annotations for 21 rare genetic diseases, we extracted 18,631 candidate disease-treatment curations, 538 of which were confirmed and transferred to the MAxO annotation dataset. Conclusion: The results of this project underscore the potential of generative AI to accelerate precision medicine by enabling a robust and comprehensive curation of the primary literature to represent information about diseases and procedures in a structured fashion. Although we focused on MAxO in this project, similar approaches could be taken for other biomedical curation tasks.