bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral venous thrombosis and miliary tuberculosis: a case report from Syria
Authors: Labbad Ibrahim , Hamzeh Ghassan 
Published: April 2023

Background:
Cerebral venous thrombosis (CVT) is a relatively common disease. Risk factors for CVT include pregnancy, cancer, autoimmune diseases, and hypercoagulation. Acute and chronic meningitis are also considered predisposing conditions for CVT. Cases of CVT associated with tuberculous meningitis and miliary tuberculosis (TB) are rare in the medical literature, and here the authors report the first case report from Middle East.

Case presentation:
The authors present a 33-year-old female patient diagnosed initially with CVT to discover the presence of tuberculous meningitis and miliary TB.

Clinical discussion:
CVT is an urgent condition and the outcome is usually good when treated quickly. The mechanisms of TB causing thrombosis are endothelial injury, slow venous flow, and increased platelet aggregation. The clinical presentation of CVT can be confused and falsely attributed to TB Meningitis.

Conclusion:
Infectious causes of CVT should always be remembered, especially TB should be in mind in developing countries.
Bronchial carcinoid misdiagnosed as COVID pneumonia: a case report
Authors: Mishra Sarmendra , Karki Saurab , Baral Surakshya , Regmi Aavishkar Raj , Gurung Adarsh , Gyawali Pramisa , Rokaya Pranjal , Pandey Sushmita 
Published: April 2023

Introduction:Bronchial carcinoid tumours are rare, slow-growing, malignant, Low-grade neuroendocrine tumours that arise from Enterochromaffin (Kulchitsky) cells and are usually detected typically as indolent and solitary tumours. Approximately 2% of all lung tumours are bronchial carcinoid tumours.Case presentation:The authors report a case of 55-years-old man who presented with a history of cough for 1 month and was initially diagnosed with a case of COVID-19. Then he was treated as a case of pneumonia as seen on high-resolution computed tomography. Later, contrast-enhanced computed tomography and bronchoscopy-guided biopsy were done which revealed a right lower lobe neuroendocrine tumour (carcinoid), which was successfully resected.Clinical discussion:The majority of typical carcinoids are located in the central airways leading to bronchial obstruction with recurrent pneumonia, chest pain, and wheezing. During the COVID-19 pandemic, lung cancer patients were at higher risk of being affected by COVID-19. This study emphasizes that early identification and differential diagnosis are extremely difficult in the absence of comprehensive study and workup as the clinical and imaging findings of COVID-19 may resemble lung cancer. Although hilar and mediastinal lymph nodes are the most common metastatic sites for typical carcinoids, most lymphadenopathies are caused by a reactive inflammatory reaction.Conclusion:Bronchial carcinoids are uncommon, malignant neuroendocrine tumours for which the only curative management is complete surgical resection. With full resection, the result of typical carcinoids with lymph node metastases is favourable.
Metastatic squamous cell carcinoma of the lung to the thyroid gland presented as nodular goiter: a rare case report
Authors: Al-janabi Moatasem Hussein , Zainab Haneen , Wannous Hiba , Dowaji Maria , Zainab Deema , Rasheed Omeed , Kannan Samir , Issa Rana 
Published: April 2023

Introduction and importance:
Metastasis of squamous cell lung carcinoma to the thyroid gland is an extremely rare event. It frequently metastasizes to lymph nodes, liver, adrenal glands, bone, brain, and pleura. Among the lung carcinomas metastasizing to the thyroid, adenocarcinomas are the most common followed by squamous cell carcinomas (SCCs).

Case presentation:
A 58-year-old male patient presented with bilateral neck swelling. Fine needle aspiration is performed and was undetermined. Ultrasonography of the neck demonstrated multiple hypoechoic nodules with thyroid enlargement. The patient was diagnosed with nodular goitre and he underwent a total thyroidectomy. Microscopically, the Hematoxylin and eosin-stained sections revealed thyroid follicles with sheets composed of polygonal cells with pleomorphic nuclei, prominent nucleoli, and a moderate amount of eosinophilic cytoplasm. Keratin pearls were present. Based on histopathological and clinical findings, the final diagnosis was metastatic SCC to the thyroid gland.

Clinical discussion:
Clinically, patients with thyroid metastasis presented with nonspecific symptoms such as thyroid nodule or goitre, cervical discomfort, dyspnoea, dysphagia, or dysphonia. Chemotherapy is used in the case of a poly metastatic tumour and radiotherapy as a palliative treatment whereas radioiodine treatment is not indicated for thyroid metastases.

Conclusion:
Diagnosis of SCC in the thyroid gland as a primary or metastatic neoplasm is a significant challenge. In the absence of specific clinical or radiological signs, pathological studies remain the gold standard for diagnosis.
Why Babies die in the first 7 days after birth in Somalia Region of Ethiopia?
Authors: Mekebo Gizachew G. , Aga Gudeta , Gondol Ketema B. , Regesa Belema H. , Woldeyohannes Birhanu , Wolde Temesgen S. , Tadesse Getachew , Galdassa Agassa , Adebe Kebede L. , Ketema Hirko 
Published: April 2023

Introduction:
Early neonatal death, which occurs during the prenatal period, is defined as the death of a newborn between 0 and 7 days after birth. It is one of the major public health problems in several developing countries. This study aimed to determine the early neonatal mortality rate and identify determinants of early neonatal mortality in Somalia region of Ethiopia.

Methods:
The data used for this study were drawn from the 2019 Ethiopia Mini Demographic and Health Survey (2019 EMDHS) data. A multivariable logistic regression model was used to identify the determinants of early neonatal mortality. Adjusted odds ratio (AOR) with 95% CI was used to examine the association of factors with early neonatal mortality.

Results:
A total of 637 live births were included in this study. The early neonatal mortality rate in the study was 44 (95% CI: 31, 65) deaths per 1000 live births. Male babies (AOR: 1.628; 95% CI: 1.152–4.895), babies delivered at home (AOR: 2.288; 95% CI: 1.194–6.593), and babies born from uneducated mothers (AOR: 2.130; 95% CI: 1.744–6.100) were at increased risk of death in the first 7 days of life after birth. Contrarily, decreased risk of death of babies in the first 7 days of life after birth was associated with urban residence (AOR: 0.669; 95% CI: 0.033–0.721) and singleton (AOR: 0.345; 95% CI: 0.070–0.609).

Conclusion:
The early neonatal mortality rate in the region was high. The study revealed that sex of child, place of residence, birth type, mother’s educational level, and place of delivery were the determinants of the death of babies in the first 7 days of life after birth. Hence, providing health education to uneducated mothers and enhancing institutional delivery is recommended to minimize the early neonatal mortality rate in the region.
Validation and Extension of the Association Between Potentially Excess Oxygen Exposure and Death in Mechanically Ventilated Children
Authors: Geva Alon , Akhondi-Asl Alireza , Mehta Nilesh M. 
Published: April 2023

OBJECTIVES:
“Cumulative excess oxygen exposure” (CEOE)—previously defined as the mean hourly administered Fio
2 above 0.21 when the corresponding hourly Spo
2 was 95% or above—was previously shown to be associated with mortality. The objective of this study was to examine the relationship among Fio
2, Spo
2, and mortality in an independent cohort of mechanically ventilated children.

DESIGN:
Retrospective cross-sectional study.

SETTING:
Quaternary-care PICU.

PATIENTS:
All patients admitted to the PICU between 2012 and 2021 and mechanically ventilated via endotracheal tube for at least 24 hours.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Among 3,354 patients, 260 (8%) died. Higher CEOE quartile was associated with increased mortality (p = 0.001). The highest CEOE quartile had an 87% increased risk of mortality (95% CI, 7–236) compared with the first CEOE quartile. The hazard ratio for extended CEOE exposure, which included mechanical ventilation data from throughout the patients’ mechanical ventilation time rather than only from the first 24 hours of mechanical ventilation, was 1.03 (95% CI, 1.02–1.03).

CONCLUSIONS:
Potentially excess oxygen exposure in patients whose oxygen saturation was at least 95% was associated with increased mortality.
Increased 68Ga-FAPI Activity in Hepatic Inflammatory Myofibroblastoma
Authors: Ou Lei , Zhou Yue , Sun Rui , Zhang Chunyin , Chen XiaoLiang 
Published: April 2023

Abstract
Hepatic inflammatory myofibroblastoma is an uncommon borderline tumor. We present 68Ga-FAPI PET/CT findings of hepatic inflammatory myofibroblastoma in a 58-year-old man. The rare hepatic inflammatory myofibroblastoma demonstrated intense tracer uptake on 68Ga-FAPI PET/CT. This case demonstrates the potential value of 68Ga-FAPI PET/CT for the evaluation of hepatic inflammatory myofibroblastoma.
Using Laser Speckle Contrast Imaging to Quantify Perfusion Quality in Kidney and Pancreas Grafts on Vascular Reperfusion: A Proof-of-Principle Study
Authors: Gopal Jeevan Prakash , Vaz Osborne , Varley Rebecca , Spiers Harry , Goldsworthy Matthew A. , Siddagangaiah Vishwanath , Lock Brian , Sharma Videha , Summers Angela , Moinuddin Zia , van Dellen David , Augustine Titus 
Published: April 2023

Introduction.
The accuracy of intraoperative graft perfusion assessment still remains subjective, with doppler examination being the only objective adjunct. Laser speckle contrast imaging (LSCI) has been used to assess intraoperative blood flow in neurosurgery and in various surgical specialties. Despite its ability to accurately quantify perfusion at the microvascular level, it has not been clinically evaluated in kidney/kidney-pancreas transplantation for perfusion characterization. We aimed to evaluate the utility of LSCI and identify objective parameters that can be quantified at reperfusion.

Methods.
This study was registered in ClinicalTrials.gov (NCT04202237). The Moor FLPI-2 blood flow imager was used in 4 patients (1 Simultaneous Pancreas and Kidney, 2 deceased, and 1 living donor kidney transplants) during reperfusion to capture reperfusion data. The following parameters were measured: flux (average speed × concentration of moving red blood cells in the sample volume), doppler centroid, total and valid pixels, valid rate, and total and valid area. Flux data were analyzed with Moor FLPI analysis software.

Results.
The perfusion characteristics and flux images correlated with initial graft function.

Conclusions.
LSCI is a safe, noncontact imaging modality that provides real-time, accurate, high-resolution, full field blood flow images and a wide range of flux data to objectively quantify organ reperfusion intraoperatively in kidney/kidney-pancreas transplantation. This modality could be used to develop a robust numerical quantification system for the evaluation and reporting of intraoperative organ perfusion, and aid intraoperative decision-making. Perfusion data could be combined with biomarkers and immunological parameters to more accurately predict graft outcomes.
Cost-effectiveness of Interventions to Increase Utilization of Kidneys From Deceased Donors With Primary Brain Malignancy in an Australian Setting
Authors: Hedley James A. , Kelly Patrick J. , Wyld Melanie , Shah Karan , Morton Rachael L. , Byrnes Juliet , Rosales Brenda M. , De La Mata Nicole L. , Wyburn Kate , Webster Angela C. 
Published: April 2023

Background.
Kidneys from potential deceased donors with brain cancer are often foregone due to concerns of cancer transmission risk to recipients. There may be uncertainty around donors’ medical history and their absolute transmission risk or risk-averse decision-making among clinicians. However, brain cancer transmissions are rare, and prolonging waiting time for recipients is harmful.

Methods.
We assessed the cost-effectiveness of increasing utilization of potential deceased donors with brain cancer using a Markov model simulation of 1500 patients waitlisted for a kidney transplant, based on linked transplant registry data and with a payer perspective (Australian government). We estimated costs and quality-adjusted life-years (QALYs) for three interventions: decision support for clinicians in assessing donor risk, improved cancer classification accuracy with real-time data-linkage to hospital records and cancer registries, and increased risk tolerance to allow intermediate-risk donors (up to 6.4% potential transmission risk).

Results.
Compared with current practice, decision support provided 0.3% more donors with an average transmission risk of 2%. Real-time data-linkage provided 0.6% more donors (1.1% average transmission risk) and increasing risk tolerance (accepting intermediate-risk 6.4%) provided 2.1% more donors (4.9% average transmission risk). Interventions were dominant (improved QALYs and saved costs) in 78%, 80%, and 87% of simulations, respectively. The largest benefit was from increasing risk tolerance (mean +18.6 QALYs and AU$2.2 million [US$1.6 million] cost-savings).

Conclusions.
Despite the additional risk of cancer transmission, accepting intermediate-risk donors with brain cancer is likely to increase the number of donor kidneys available for transplant, improve patient outcomes, and reduce overall healthcare expenditure.
VoroIF-GNN: Voronoi tessellation-derived protein-protein interface assessment using a graph neural network
Authors: Olechnovič Kliment , Venclovas Česlovas 
Published: April 2023

AbstractWe present VoroIF-GNN, a novel single-model method for assessing inter-subunit interfaces in protein-protein complexes. Given a multimeric protein structural model, we derive interface contacts from the Voronoi tessellation of atomic balls, construct a graph of those contacts, and predict accuracy of every contact using an attention-based graph neural network. The contact-level predictions are then summarized to produce whole interface-level scores. VoroIF-GNN was blindly tested for its ability to estimate accuracy of protein complexes during CASP15 and showed strong performance in selecting the best multimeric model out of many. The method implementation is freely available athttps://klimentolechnovic.github.io/voronota/expansion_js/.
Tracking insulin- and glucagon-expressing bihormonal cells during differentiation using anINSULINandGLUCAGONdouble reporter human embryonic stem cell line
Authors: Mar Samantha , Filatov Ekaterina , Nian Cuilan , Sasaki Shugo , Zhang Dahai , Lynn Francis C. 
Published: April 2023

SummaryHuman embryonic stem cell (hESC)-derived pancreatic alpha and beta cells can be used to develop cell replacement therapies to treat diabetes. However, recent published differentiation protocols yield varying amounts of alpha and beta cells amidst heterogeneous cell populations. To visualize and isolate hESC-derived alpha and beta cells, we generated aGLUCAGON-2A- mScarletandINSULIN-2A-EGFPdual fluorescent reporter (INSEGFPGCGmScarlet) hESC line using CRISPR/Cas9. We established robust expression of EGFP and mScarlet fluorescent proteins in insulin- and glucagon-expressing cells respectively without compromising the differentiation or function of these cells. We also showed the insulin- and glucagon-expressing bihormonal population at the maturing endocrine cell stage (Stage 6) lose insulin expression over time, while maintaining an alpha-like expression profile, suggesting these bihormonal cells are preferentially fated to become alpha-like cellsin vitro. Together, the INSEGFPGCGmScarlethESC line provides an efficient strategy for tracking populations of hESC-derived beta- and alpha-like cells.
Validating a low-cost, open-source, locally manufactured workstation and computational pipeline for automated histopathology evaluation using deep learning
Authors: Choudhury Divya , Dolezal James , Dyer Emma , Kochanny Sara , Ramesh Siddi , Howard Frederick M. , Margalus Jayson R. , Schroeder Amelia , Schulte Jefree , Garassino Marina C. , Kather Jakob N. , Pearson Alexander T. 
Published: April 2023

AbstractDeployment and access to state-of-the-art diagnostic technologies remains a fundamental challenge in providing equitable global cancer care to low-resource settings. The expansion of digital pathology in recent years and its interface with computational biomarkers provides an opportunity to democratize access to personalized medicine. Here we describe a low-cost platform for digital side capture and computational analysis composed of open-source components. The platform provides low-cost ($200) digital image capture from glass slides and is capable of real-time computational image analysis using an open-source deep learning (DL) algorithm and Raspberry Pi ($35) computer. We validate the performance of deep learning models’ performance using images captured from the open-source workstation and show similar model performance when compared against significantly more expensive standard institutional hardware.
DECODING COMPLEXITY IN BIOMOLECULAR RECOGNITION OF DNA I-MOTIFS
Authors: Yazdani Kamyar , Seshadri Srinath , Tillo Desiree , Vinson Charles , Schneekloth John S. 
Published: April 2023

AbstractDNA i-motifs (iMs) are non-canonical C-rich secondary structures implicated in numerous cellular processes. Though iMs exist throughout the genome, our understanding of iM recognition by proteins or small molecules is limited to a few examples. We designed a DNA microarray containing 10,976 genomic iM sequences to examine the binding profiles of four iM-binding proteins, mitoxantrone, and the iMab antibody. iMab microarray screens demonstrated that pH 6.5, 5% BSA buffer was optimal, and fluorescence was correlated with iM C-tract length. hnRNP K broadly recognizes diverse iM sequences, favoring 3-5 cytosine repeats flanked by thymine-rich loops of 1-3 nucleotides. Array binding mirrored public ChIP-Seq datasets, in which 35% of well-bound array iMs are enriched in hnRNP K peaks. In contrast, other reported iM-binding proteins had weaker binding or preferred G-quadruplex (G4) sequences instead. Mitoxantrone broadly binds both shorter iMs and G4s, consistent with an intercalation mechanism. These results suggest that hnRNP K may play a role in iM-mediated regulation of gene expressionin vivo, whereas hnRNP A1 and ASF/SF2 are possibly more selective in their binding preferences. This powerful approach represents the most comprehensive investigation of how biomolecules selectively recognize genomic iMs to date.
Alternative splicing impacts microRNA regulation within coding regions
Authors: Hackl Lena Maria , Fenn Amit , Louadi Zakaria , Baumbach Jan , Kacprowski Tim , List Markus , Tsoy Olga 
Published: April 2023

ABSTRACTMicroRNAs (miRNAs) are small non-coding RNA molecules that bind to target sites in different gene regions and regulate post-transcriptional gene expression. Approximately 95% of human multi-exon genes can be spliced alternatively, which enables the production of functionally diverse transcripts and proteins from a single gene. Through alternative splicing, transcripts might lose the exon with the miRNA target site and become unresponsive to miRNA regulation. To check this hypothesis, we studied the role of miRNA target sites in both coding and noncoding regions using six cancer data sets from The Cancer Genome Atlas (TCGA). First, we predicted miRNA target sites on mRNAs from their sequence using TarPmiR. To check whether alternative splicing interferes with this regulation, we trained linear regression models to predict miRNA expression from transcript expression. Using nested models, we compared the predictive power of transcripts with miRNA target sites in the coding regions to that of transcripts without target sites. Models containing transcripts with target sites perform significantly better. We conclude that alternative splicing does interfere with miRNA regulation by skipping exons with miRNA target sites within the coding region.
Suprabasal cells retaining stem cell identity programs drive basal cell hyperplasia in eosinophilic esophagitis
Authors: Clevenger Margarette H. , Karami Adam L. , Carlson Dustin A. , Kahrilas Peter J. , Gonsalves Nirmala , Pandolfino John E. , Winter Deborah R. , Whelan Kelly A. , Tétreault Marie-Pier 
Published: April 2023

AbstractEosinophilic esophagitis (EoE) is an esophageal immune-mediated disease characterized by eosinophilic inflammation and epithelial remodeling, including basal cell hyperplasia (BCH) and loss of differentiation. Although BCH correlates with disease severity and with persistent symptoms in patients in histological remission, the molecular processes driving BCH remain poorly defined. Here, we demonstrate that despite the presence of BCH in all EoE patients examined, no increase in basal cell proportion was observed by scRNA-seq. Instead, EoE patients exhibited a reduced pool ofKRT15+ COL17A1+quiescent cells, a modest increase inKI67+dividing epibasal cells, a substantial increase inKRT13+ IVL+suprabasal cells, and a loss of differentiated identity in superficial cells. Suprabasal and superficial cell populations demonstrated increased quiescent cell identity scoring in EoE with the enrichment of signaling pathways regulating pluripotency of stem cells. However, this was not paired with increased proliferation. Enrichment and trajectory analyses identified SOX2 and KLF5 as potential drivers of the increased quiescent identity and epithelial remodeling observed in EoE. Notably, these findings were not observed in GERD. Thus, our study demonstrates that BCH in EoE results from an expansion of non-proliferative cells that retain stem-like transcriptional programs while remaining committed to early differentiation.
Nfe2l1-mediated proteasome function controls muscle energy metabolism in obesity
Authors: Lemmer Imke L. , Haas Daniel T. , Willemsen Nienke , Kotschi Stefan , Toksöz Irmak , Gjika Ejona , Khani Sajjad , Rohm Maria , Diercksen Nick , Nguyen Phong B.H. , Menden Michael P. , Egu Desalegn T. , Waschke Jens , Larsen Steen , Ma Tao , Gerhart-Hines Zachary , Herzig Stephan , Dyar Kenneth , Krahmer Natalie , Bartelt Alexander 
Published: April 2023

AbstractMuscle function is an important denominator of energy balance and metabolic health. Adapting the proteome to energetic challenges, in response to diet or fasting, is facilitated by programs of proteostasis, but the adaptive role of the ubiquitin-proteasome system (UPS) in muscle remains unclear. Here, using a multi-omics approach, we uncover that the distinct metabolic condition of obesity is associated with recalibration of the UPS in muscle. Interestingly, obesity is associated with the activation of the transcription factor Nuclear factor, erythroid derived 2,- like 1 (Nfe2l1, also known as Nrf1), and loss of myocyte Nfe2l1 diminishes proteasomal activity and leads to hyperubiquitylation. Mice lacking Nfe2l1 display hormetic energy metabolism and resistance to diet-induced obesity, associated with a lean phenotype and muscle fiber type switching. In conclusion, we define a new adaptive role for UPS in remolding of muscle proteome and function, which is controlled by fine-tuning of proteasome function by Nfe2l1.