bluuebunny/crossref_metadata_2025 huggingface dataset:
SUMOylated IL-33 in the nucleus stabilizes the transcription factor IRF1 in hepatocellular carcinoma cells to promote immune escape
Authors: Wang Zengbin , Pan Banglun , Qiu Jiacheng , Zhang Xiaoxia , Ke Xiaoling , Shen Shuling , Wu Xiaoxuan , Yao Yuxin , Tang Nanhong
Published: March 2023

Interleukin-33 (IL-33) functions both as a secreted cytokine and as a nuclear factor, with pleiotropic roles in cancer and immunity. Here, we explored its role in hepatocellular carcinoma (HCC) and identified that a posttranslational modification altered its nuclear activity and promoted immune escape for HCC. IL-33 abundance was overall decreased but more frequently localized to the nucleus in patient HCC tissues than in normal liver tissues. In human and mouse HCC cells in culture and in vivo, IL-33 overexpression inhibited proliferation and repressed the abundance of programmed death ligand 1 (PD-L1) at the transcriptional level by promoting the ubiquitin-dependent degradation of interferon regulatory factor 1 (IRF1). However, this interaction was disrupted by SUMOylation of IL-33 at Lys
54
mediated by the E3 ligase RanBP2. IL-33 SUMOylation correlated with its nuclear localization in HCC cells and tumors. An increase in SUMOylated IL-33 in HCC cells in cocultures and in vivo stabilized IRF1 and increased PD-L1 abundance and chemokine IL-8 secretion, which prevented the activation of cytotoxic T cells and promoted the M2 polarization of macrophages, respectively. Mutating the SUMOylation site in IL-33 reversed these effects and suppressed tumor growth. These findings indicate that SUMOylation of nuclear IL-33 in HCC cells impairs antitumor immunity.
IL-6 drives hepatocyte dedifferentiation
Authors: VanHook Annalisa M.
Published: March 2023

Injury-induced hepatocyte reprogramming depends on a proinflammatory cytokine from Kupffer cells.
The Dual Benefit of Sulfasalazine on Pneumocystis Pneumonia-Related Immunopathogenesis and Antifungal Host Defense Does Not Require IL-4Rα-Dependent Macrophage Polarization
Authors: Zhang Zhuo-Qian , Gigliotti Francis , Wright Terry W.
Published: March 2023

Pneumocystis
is a respiratory fungal pathogen that is among the most frequent causes of life-threatening pneumonia (PcP) in immunocompromised hosts. Alveolar macrophages play an important role in host defense against
Pneumocystis
, and several studies have suggested that M2 polarized macrophages have anti-
Pneumocystis
effector activity.
The C-Terminal Acid Phosphatase Module of the RNase HI Enzyme RnhC Controls Rifampin Sensitivity and Light-Dependent Colony Pigmentation of Mycobacterium smegmatis
Authors: Dupuy Pierre , Glickman Michael S.
Published: March 2023

Mycobacteria encode multiple RNase H enzymes, with RNase HI being essential for viability. Here, we examine additional functions of RNase H enzymes in mycobacteria.
A Single Surface-Exposed Amino Acid Determines Differential Neutralization of AAV1 and AAV6 by Human Alpha-Defensins
Authors: Porter Jessica M. , Oswald Mackenzi S. , Sharma Anjali , Emmanuel Shanan , Kansol Austin , Bennett Antonette , McKenna Robert , Smith Jason G.
Published: March 2023

The ability of adeno-associated viruses (AAVs) to infect and deliver genetic material to a range of cell types makes them favorable gene therapy vectors. However, AAV vectors encounter a wide variety of host immune factors throughout the body, which can impede efficient gene delivery.
Exploring Host-Binding Machineries of Mycobacteriophages with AlphaFold2
Authors: Cambillau Christian , Goulet Adeline
Published: March 2023

Mycobacteria include both saprophytes, such as the model system
Mycobacterium smegmatis
, and pathogens, such as
Mycobacterium tuberculosis
and
Mycobacterium abscessus
, that are poorly responsive to antibiotic treatments and pose a global public health problem. Mycobacteriophages have been collected at a very large scale over the last decade, and they have proven to be valuable tools for mycobacteria genetic manipulation, rapid diagnostics, and infection treatment.
The Sensory Histidine Kinase CusS of Escherichia coli Senses Periplasmic Copper Ions
Authors: Rismondo Jeanine , Große Cornelia , Nies Dietrich H.
Published: March 2023

Homeostasis of essential-but-toxic transition metal cations such as Zn(II) and Cu(II)/Cu(I) is an important contributor to the fitness of environmental bacteria and pathogenic bacteria during their confrontation with an infected host. Highly efficient removal of threatening concentrations of these metals can be achieved by the combined actions of an inner membrane with a transenvelope efflux system, which removes periplasmic ions after their export from the cytoplasm to this compartment.
Comprehensive Analysis of Antimicrobial, Heavy Metal, and Pesticide Residues in Commercial Organic Fertilizers and Their Correlation with Tigecycline-Resistant
tet
(X)-Variant Genes
Authors: He Tao , Li Jun , Gong Lan , Wang Yang , Li Ruichao , Ji Xing , Luan Fengting , Tang Minmin , Zhu Lei , Wei Ruicheng , Wang Ran
Published: March 2023

An antimicrobial resistance gene (ARG) is considered a novel contaminant for the environment. Most animal feces are usually made into commercial organic fertilizers in China and will pose a threat to the farmland soil and agricultural product if fertilizers harboring clinically significant antimicrobial-resistant (AMR) genes are applied on farmland.
Transmission of SARS-CoV-2 Omicron Variant under a Dynamic Clearance Strategy in Shandong, China
Authors: Xu Yifei , Liu Ti , Li Yan , Wei Xuemin , Wang Zhaoguo , Fang Ming , Zhang Yuwei , Zhang Huaning , Zhang Lifang , Zhang Jinbo , Xu Jin , Tian Yunlong , He Nianzheng , Zhang Yuhan , Wang Yao , Yao Mingxiao , Pang Bo , Wang Shuang , Wen Hongling , Kou Zengqiang
Published: March 2023

Starting in March 2022, the Omicron epidemic caused a large wave of COVID-19 cases in China. Shandong was one of the most affected regions during this epidemic but was also among those areas that were able to quickly contain the transmission.
Oral Administration of Universal Bacterium-Vectored Nucleocapsid-Expressing COVID-19 Vaccine is Efficacious in Hamsters
Authors: Jia Qingmei , Bielefeldt-Ohmann Helle , Maison Rachel M. , Hartwig Airn , Masleša-Galić Saša , Bowen Richard A. , Horwitz Marcus A.
Published: March 2023

The COVID-19 pandemic continues to rage into its fourth year worldwide. To protect the world’s population most effectively from severe disease, hospitalization, and death, a vaccine is needed that is resistant to rapidly emerging viral variants of the causative agent SARS-CoV-2, inexpensive to manufacture, store, and transport, and easy to administer.
A Longitudinal Characterization of the Seminal Microbiota and Antibiotic Resistance in Yearling Beef Bulls Subjected to Different Rates of Gain
Authors: Webb Emily M. , Holman Devin B. , Schmidt Kaycie N. , Crouse Matthew S. , Dahlen Carl R. , Cushman Robert A. , Snider Alexandria P. , McCarthy Kacie L. , Amat Samat
Published: March 2023

Increasing evidence from human and other animal species supports the existence of a commensal microbiota in semen and that this seminal microbiota may influence not only sperm quality and fertility but also female reproduction. Seminal microbiota in bulls and its evolution and factors shaping this community, however, remain largely underexplored.
Interference Transport in a Two-Dimensional Topological Insulator in a CdHgTe Quantum Well
Authors: Ryzhkov M. S. , Kozlov D. A. , Khudaiberdiev D. A. , Kvon Z. D. , Mikhailov N. N.
Published: March 2023

Interference transport in mesoscopic samples of a two-dimensional topological insulator in CdHgTe quantum wells is studied for the first time. It is established that quasi-ballistic edge transport in such an insulator exists at lengths up to 10 µm. In this transport regime, almost periodic Aharonov–Bohm oscillations caused by the formation of closed loops with a characteristic size of about 200 nm by edge states are found. The phase coherence length in the two-dimensional topological insulator is determined for the first time from the measured temperature dependence of their amplitude.
Two-Photon Laser Lithography of Functional Microstructures of Integrated Photonics: Waveguides, Microcavities, and Prism Input/Output Adapters of Optical Radiation
Authors: Maydykovskiy A. I. , Apostolov D. A. , Mamonov E. A. , Kopylov D. A. , Dagesyan S. A. , Murzina T. V.
Published: March 2023

The development and optimization of methods for creating functional elements of micron and sub-micron sizes for photonic integrated circuits is one of the main tasks of nanophotonics. Two-photon laser lithography is actively developing now to form three-dimensional structures with subwave resolution. Results of this development are reported and it is shown that the use of optimized lithography schemes, the spatial filtering of laser beam used, and the introduction of laser dyes into polymer lead to the formation of optically homogeneous high-quality bulk microstructures with characteristic features down to 300 nm with necessary functional properties. The capabilities of optimized two-photon laser lithography are demonstrated by examples of ring microcavities and optical waveguides with prism input/output adapters located above a substrate. Optical losses upon the coupling of 405-nm radiation into a waveguide using a printed prism adapter was no more than 1.25 dB.
Charge Density and Mobility of Charge Density Waves in the Quasi-One-Dimensional Conductor NbS3
Authors: Zybtsev S. G. , Pokrovskii V. Ya. , Nikonov S. A. , Maizlakh A. A. , Zaitsev-Zotov S. V.
Published: March 2023

Three charge density waves (CDWs), two of which are formed above room temperature, are observed in the NbS3 monoclinic phase (NbS3-II). The charge density and mobility in the high-field limit have been determined for each of three CDWs in this work using the synchronization effect of CDWs in high-frequency fields. It has been found that the mobility of each CDW in this limit is approximately equal to the normal-state mobility of quasiparticles condensed in it. Furthermore, correlation has been observed between the temperature dependences of mobilities of CDWs and quasiparticles. The results of this work refresh problems of a mechanism of the limit conductivity of CDWs and of the distribution of CDWs between atomic chains in the unit cell.
Dynamical Correlations in the Ground State: Transitions between One-Phonon Nuclear States
Authors: Shitov M. I. , Kamerdzhiev S. P. , Tolokonnikov S. V.
Published: March 2023

The probabilities of the E1 transition between the first $${{2}^{ + }}$$ and $${{3}^{ - }}$$ excited levels in nuclei with pairing have been calculated within the self-consistent many-body nuclear theory and Green’s function method. Calculations for a long chain of even–even tin isotopes have been performed for the first time. The known Fayans energy density functional has been used to calculate the characteristics of phonons and E1 transitions between excited states. A good description has been achieved for existing experimental data for the reduced probabilities of E1 transitions between the first one-phonon states for the 116–124Sn isotopes but not for the 112Sn and 114Sn isotopes. Possible reasons for this discrepancy have been discussed; the most probable reason is the deformation in the ground or excited states. It has been shown that new dynamical three-quasiparticle correlations in the ground state should be taken into account to explain the experimental data for 116–124Sn.
Hyperferritinaemia following intrauterine transfusions for Rh isoimmunisation
Authors: Anne Rajendra Prasad , Sundaram Venkataseshan , Dutta Sourabh , Kumar Praveen
Published: March 2023

Intrauterine transfusion is one of the mainstays of treatment in isoimmunised pregnancies guided by the changes in middle cerebral artery Doppler of the fetus. The common postnatal complications associated with Rh isoimmunisation are high unconjugated bilirubin requiring blood exchange transfusions, cholestasis due to bile inspissation, thrombocytopenia and anaemia. Hyperferritinaemia is an uncommon adverse effect observed in Rh isoimmunised pregnancies. In this case report, we describe the clinical course of a Rh isoimmunised neonate with hyperferritinaemia and transfusion acquired cytomegalovirus disease which resolved. Iron chelation therapy was not necessary.
Rheumatoid meningitis: a rare cause of unilateral pachymeningitis
Authors: Grose Daniel , Linger Matthew , Tinni Samara , Sahathevan Ramesh
Published: March 2023

An 87-year-old woman with quiescent rheumatoid arthritis, not on immunosuppressive therapy, presented with unilateral arm weakness, confusion and visual hallucinations. There were no infective symptoms or history of malignancy. Cerebrospinal fluid (CSF) analysis demonstrated lymphocytosis and raised protein, without flow cytometric or cytological abnormalities. Viral, bacterial, mycobacterial and fungal testing of CSF and serum were negative. MRI brain indicated unilateral leptomeningeal enhancement. There was no evidence of occult malignancy on CT imaging of the chest, abdomen and pelvis. Rheumatoid factor and anticyclic citrullinated peptide were strongly positive. The patient declined meningeal biopsy but responded to treatment with corticosteroid therapy.
Spontaneous partial regression of a microcystic jejunal mesenteric lymphangioma and a proposed management algorithm
Authors: Tan Dominic Ti Ming , Chok Aik Yong , Farah Benjamin Livingston , Yan Yet Yen , Toh Ee-Lin
Published: March 2023

Mesenteric lymphangiomas are relatively rare, with clinical symptoms ranging from an asymptomatic presentation to an acute abdomen. The natural history and biological behaviour of this entity can range from slow indolent lesions to aggressive tumours with a risk of malignant transformation. Spontaneous regression of a mesenteric lymphangioma is rare. We herein report a case of a jejunal mesenteric lymphangioma that was initially detected incidentally in an asymptomatic patient with a subsequent sudden increase in size with resulting surrounding mass effect after 9 months and a spontaneous partial regression at surgical resection. Our case is the first reported case which outlines a period in the natural history and evolution of microcystic mesenteric lymphangioma, illustrating the sudden enlargement likely attributable to spontaneous and self-limiting haemorrhage and subsequent partial regression at surgical resection. We thenceforth propose a possible management algorithm for adult patients with mesenteric lymphangiomas.
A simple procedure in a complex patient: perioperative takotsubo cardiomyopathy
Authors: Jothin Arvind , Raj John Prakash , Thiruvenkatarajan Venkatesan
Published: March 2023

Takotsubo cardiomyopathy (TTC) is a rare but life-threatening condition that is still not completely understood. Characterised by rapidly reversible ventricular dysfunction without any prior coronary artery disease, it can imitate a myocardial infarction and lead to death if not managed appropriately. This report examines a case of intraoperative cardiac arrest in a patient with no previous cardiac disease, and discusses the factors that may have precipitated this event, as well as the ways of distinguishing the cause of the arrest based on clinical course and investigations, eventually leading to a diagnosis of TTC.
Spontaneous extrusion of a dexamethasone intravitreal implant (Ozurdex)
Authors: Ong Jessica , Davidoss Nishant Hemanth , Bhosale Anant , Balaratnasingam Chandrakumar
Published: March 2023

A 59-year-old man with diabetic macular oedema was treated with a dexamethasone intravitreal implant (Ozurdex) to his right eye. Immediately after injection, the implant was noted to have extruded into the perilimbal subconjunctival space. The remnants of the implant were expeditiously removed the following day to avoid corneal decompensation and permanent corneal oedema. Endothelial decompensation secondary to the migration of dexamethasone implants into the subconjunctival space or anterior chamber is a recognised complication of Ozurdex injection. The patient recovered well postoperatively with no further complications. He was planned for a new Ozurdex implant 1 month later.
Trimethoprim-induced hyponatremia mimicking SIADH in a patient with pulmonary nocardiosis: use of point-of-care ultrasound in apparent euvolemic hypotonic hyponatremia
Authors: Saha Biplab K , Chong Woon Hean Hean
Published: March 2023

A 72-year-old man with chronic obstructive pulmonary disease and depression presented to the emergency department (ED) with progressive worsening of shortness of breath. He required intubation and mechanical ventilation. The patient improved with therapy, but his endotracheal aspirate culture was positive forNocardia cyriacigeorgica. The patient was started on high dose Bactrim and discharged. He presented to the office 5 days later with confusion, and his serum sodium was 113 mmol/L. Based on a euvolemic physical examination, consistent serum and urine studies, he was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) likely from citalopram. However, treatment for SIADH failed to improve his serum sodium level. A bedside ultrasound revealed an inferior vena cava diameter of 0.7 cm with a complete inspiratory collapse that was inconsistent with SIADH. The patient was correctly diagnosed with salt-losing nephropathy from trimethoprim, and the medication was discontinued. He received therapy initially with intravenous normal saline and then salt tablets. His sodium improved within 2 weeks.
Management of esotropia: hypotropia in neurofibromatosis type 1 – simulating myopic strabismus fixus
Authors: Jain Mayank , Kekunnaya Ramesh
Published: March 2023

A 28-year-old man presented with a progressive inward deviation of the left eye in the last 4 years. Examination revealed −3 abduction and elevation deficit in the left eye with 50 prism diopters (PD) esotropia and 12 PD of hypotropia. The patient had multiple fibromas on the forearms with pulsatile globe and was diagnosed as neurofibromatosis type 1. Myopic strabismus fixus was suspected. MRI revealed left temporal lobe herniation through a dysplastic sphenoid wing, compressing the posterior half of the superior rectus and lateral rectus muscles, resulting in an esotropia-hypotropia complex. Surgical treatment involved suture myopexy (Yokoyama’s technique) of the left superior rectus and lateral rectus muscles with a 6.5 mm left medial rectus recession. Two months postoperatively, the patient had minimal residual esotropia and hypotropia. MRI orbits should always be performed in high myopes with strabismus to assess extraocular muscle pathways.
Superior vena caval obstruction: a rare presentation of Behcet’s disease
Authors: Nair Avinash Anil , Christopher D J , Moidu Fazil , Chandran Divya
Published: March 2023

A 25-year-old Indian man presented with low-grade fever followed by gradually increasing swelling of neck and face. Physical examination showed bilateral neck swelling, facial swelling and dilated veins in the upper chest. Superior vena cava (SVC) obstruction due to an underlying malignancy was suspected. CT thorax showed large saccular aneurysm with thrombosis of bilateral subclavian arteries of which the right one caused external compression of right innominate vein draining into the SVC. A history of recurrent oral and scrotal ulcers was obtained following which skin pathergy test was done, which was suggestive of a diagnosis of Behcet’s disease (BD). He responded to treatment with steroids and azathioprine. This report illustrates that rare nonmalignant cause such as BD could also present with SVC obstruction.
Reversible optic neuropathy secondary to metronidazole
Authors: Anwyll Natalie , Gerry Paul , Gormley Joe
Published: March 2023

Metronidazole is a nitroimidazole antibiotic used in treating anaerobic bacteria and protozoal infections. It was first licensed for the treatment of Trichomonas vaginalis but is now used in the management of various gastrointestinal and genitourinary infections. Many neurological side effects are well documented, although there is scarce literature illustrating optic neuropathy secondary to metronidazole. We describe a case report of a 36-year-old man who presented with symptomatically reduced central visual loss on a background of a 2-year history of metronidazole use for a perianal fistula. Electrophysiology demonstrated bilateral optic neuropathy, with pattern visual evoked potential traces demonstrating marked latency and small amplitude responses of the P100 waves, which improved to within normal limits on cessation of metronidazole. This case study demonstrates clinical and electrophysiological reversibility of optic neuropathy secondary to high dose and prolonged metronidazole use.
Vallecular cyst: a dangerous cause of failure to thrive in infants
Authors: Lee Pei-Shan , Larrow Annie , Stover Laurie Bernard , Gardiner Michael
Published: March 2023

A 2-month-old full-term female infant with medical history of situs inversus totalis presented to the emergency department with congestion and abnormal breathing. She was discovered to have failure to thrive (FTT) and subsequently admitted. Investigations revealed a large vallecular mass at the base of her tongue which was noted to cause severe, intermittent airway obstruction. The mass underwent marsupialisation by otolaryngology (ENT) and pathology confirmed a diagnosis of vallecular cyst. The patient made a full recovery and is now growing and thriving. This case emphasises the need to consider anatomic airway abnormalities in the differential diagnosis of young infants with the constellation of respiratory symptoms and FTT. Such airway abnormalities can cause life-threatening airway obstruction if not discovered.
Creatine transporter deficiency, an underdiagnosed cause of male intellectual disability
Authors: Jangid Neha , Surana Priyanka , Salmonos Gajja , Jain Vivek
Published: March 2023

X-linked creatine transporter deficiency is caused by the deficiency of the creatine transporter encoded by theSLC6A8gene on Xq28. We here report a 3-year-old boy with global developmental delay, autism and epilepsy. He had a normal MRI of the brain. Brain magnetic resonance spectroscopy (MRS) subsequently showed an abnormally small creatine peak. His high urine creatine/creatinine ratio further suggested the diagnosis, later confirmed by hemizygous mutation detected in theSLC6A8gene. His mother was also heterozygous for the same mutation. Supplementation with creatine monohydrate, arginine, and glycine (precursors of creatine) and supportive therapies, resulted in modest clinical improvement after 12 months. This case highlights the importance of doing MRS for boys with global delay/intellectual disability, autism and epilepsy even with a normal MRI of the brain, to pick up a potentially treatable cause.
Dapsone-induced DRESS after infliximab-induced vasculitis: a case of cerebral infarction in the context of multiple drug reactions
Authors: Roth Michael , Gray Jeffery T , Peterson Paul Gabriel , Clark Paul A
Published: March 2023

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a life-threatening condition characterised by peripheral eosinophilia, rash and multi-organ failure arising several weeks after exposure to the culprit medication. Although rare, DRESS syndrome triggered by specific agents has been associated with specific genetic polymorphisms more prevalent in different ethnic groups, including an association between dapsone-induced DRESS and Human Leukocyte Antigen (HLA)-B:13*01, a single nucleotide polymorphism more prevalent in those of Asian descent. DRESS and drug-related vasculitis may affect any organ system including the central nervous system (CNS), usually manifesting as encephalitis, meningitis or embolic cerebrovascular accidents related to eosinophilic cardiac disease and thrombosis. CNS vasculitis is a much rarer complication of drug reactions that may manifest as multifocal ischemia on neuroimaging. In circumstances of drug-related vasculitides, treatment with high-dose corticosteroids may lead to rapid improvement and, ultimately, resolution of associated focal neurologic deficits.
Cauda equina compression in metastatic prostate cancer
Authors: Siddiqui Raheel Shakoor , Cheruvu Manikandar Srinivas , Ansari Hamza , van Liefland Marck
Published: March 2023

A 67-year-old man presented to his general practitioner with intermittent episodes of unilateral sciatica over a 2-month period for which he was referred for an outpatient MRI of his spine. This evidenced a significant lumbar vertebral mass that showed tight canal stenosis and compression of the cauda equina. The patient was sent to the emergency department for management by orthopaedic surgeons. He was mobilising independently, pain free on arrival and without neurological deficit on assessment. Clinically, this patient presented with no red flag symptoms of cauda equina syndrome or reason to suspect malignancy. In these circumstances, National Institute for Health and Care Excellence guidelines do not support radiological investigation of the spine outside of specialist services. However, in this case, investigation helped deliver urgent care for cancer that otherwise may have been delayed. This leads to the question, do the current guidelines meet clinical requirements?
Isolated renal vein and inferior vena cava thrombosis in a young man with ulcerative colitis: diagnostic challenges and lessons learned
Authors: Sharma Aditya Prakash , Devana Sudheer Kumar , Tyagi Shantanu , Singh Shrawan Kumar
Published: March 2023

We present a case of a young man, known case of ulcerative colitis, who presented with acute onset right flank pain and haematuria. Blood workup showed leucocytosis and raised serum creatinine. Cross-sectional imaging revealed renal vein with inferior vena cava thrombosis. He had a normal infectious screen and lacked septic features pointing towards non-infectious pathology. The 24-hour urine examination revealed nephrotic range proteinuria. Further evaluation was inconclusive for any defined pathology. Empiric anticoagulation was started and patient responded miraculously with restoration of vascularity to the affected kidney and discharged in stable condition.
Supraglottic cyst in adult patient with Shabbir syndrome
Authors: Kajal Smile , Reddy Chandra Shekar , Sikka Kapil , Thakar Alok
Published: March 2023

A 29-year-old male patient presented with a history of voice change and feeling of a lump in throat for the last 20 years. He was tracheostomised at the age of 10 years. Endolaryngeal examination showed a mucosal bulge in supraglottic region arising predominantly from right side. He had multiple healed scar marks on neck, arms and elbows, and had dystrophic nail changes. MRI of the neck showed a supraglottic cyst covering glottis. The patient was diagnosed as a case of laryngo-onycho-cutaneous syndrome which is also known as Shabbir syndrome. He underwent supraglottic cyst excision via transoral ultrasonic surgery. Glottic scarring along with subglottic stenosis was found intraoperatively, which was released using carbon dioxide laser and finally Montgomery (MT) tube was inserted. The patient got his tracheostomy tube removed for the first time in 20 years. He tolerated corking of MT tube. He was able to breathe through nose and phonate using false cords.
Delayed haemolysis following artesunate in a child with profound anaemia and Coca-Cola-coloured urine
Authors: Patel Neaha , Thomson Julia , Re Ferre Lucia
Published: March 2023

An 8-year-old girl of African descent presented to the hospital with a headache, lethargy, pallor and ‘Coca-Cola’-coloured urine. She had been admitted 11 days before withPlasmodium falciparummalaria, which was successfully treated with 48 hours of parenteral artesunate. Investigations revealed signs of severe haemolytic anaemia, with a haemoglobin level of 52 g/L that reached a nadir of 10 g/L within 4 hours, in addition to haemoglobinuria, hyperbilirubinaemia and raised lactate dehydrogenase levels. She was diagnosed with post-artemisinin delayed haemolysis, which is usually self-limiting but has the potential to cause severe, life-threatening anaemia 7–21 days following malaria treatment with artesunate. There was excellent response to blood transfusion, and the child made a full recovery. This case highlights the importance of providing safety netting advice regarding signs and symptoms of anaemia to patients receiving artesunate, in addition to monitoring of haemoglobin levels in the weeks after treatment.
Radiation-induced glioblastoma of the conus medullaris from radiation treatment of cervical cancer
Authors: Pascual Juan Silvestre Grecia , Sih Ibet Marie Yap , Salise Joeanne Marie Mahinay , Munoz Edwin Lim
Published: March 2023

Radiation-induced spinal glioblastoma is an extremely rare disease with only four previously published reports in the literature. We report the fifth case, a 69-year-old woman who previously underwent treatment with brachytherapy for cervical cancer, and thereafter presented with neurologic deficits from a conus medullaris tumour. Biopsy and histopathology confirm glioblastoma, not otherwise specified. Treatment of spinal glioblastoma consists of surgery, either biopsy or excision and chemoradiation. However, results are still unsatisfactory and prognosis remains poor.
Preoperative screening endometrial cytology discovered incidental gynaecological malignancy in two patients undergoing risk-reducing salpingo-oophorectomy
Authors: Kojima Riho , Toyoshima Masafumi , Yamamoto Akihito , Suzuki Shunji
Published: March 2023

Pelvic ultrasonography and measurement of serum cancer antigen 125 (CA-125) are recommended for preoperative evaluation before performing risk-reducing salpingo-oophorectomy (RRSO). We report our experience with two patients in whom an incidental gynaecological malignancy was found using endometrial cytology as a preoperative screening test for RRSO. Patient 1 was an early 50s woman with a pathologic variant ofBRCA1. Transvaginal ultrasonography showed no endometrial abnormalities, but preoperative endometrial cytology revealed high-grade serous carcinoma. The patient underwent total hysterectomy, bilateral adnexectomy, pelvic and para-aortic lymph node dissection, and omentectomy. Patient 2 was a late 40s woman with a pathological variant ofBRCA1. Transvaginal ultrasonography showed mild enlargement of the left ovary, and her CA-125 level was elevated. Preoperative endometrial cytology revealed high-grade serous cancer. She underwent total hysterectomy, bilateral adnexectomy and omentectomy. These case reports illustrate the importance of preoperative screening—including endometrial cytology—before performing RRSO.
Experience of point-of-care HbA1c testing in the English National Health Service Diabetes Prevention Programme: an observational study
Authors: Barron Emma , Misra Shivani , English Emma , John W Garry , Sampson Michael , Bachmann Max O , Barth Julian , Oliver Nick , Alberti K G M M , Bakhai Chirag , O'Neill Simon , Young Bob , Wareham Nicholas J , Khunti Kamlesh , Jebb Susan , Smith Jenifer , Valabhji Jonathan
Published: March 2023

Introduction

To report the observations of point-of-care (POC) glycated hemoglobin (HbA1c) testing in people with non-diabetic hyperglycemia (NDH; HbA1c 42–47 mmol/mol (6.0%–6.4%)), applied in community settings, within the English National Health Service Diabetes Prevention Programme (NHS DPP).

Research design and methods

A service evaluation assessing prospectively collected national service-level data from the NHS DPP, using data from the first referral received in June 2016–October 2018. Individuals were referred to the NHS DPP with a laboratory-measured HbA1c in the NDH range and had a repeat HbA1c measured at first attendance of the program using one of three POC devices: DCA Vantage, Afinion or A1C Now+. Differences between the referral and POC HbA1c and the SD of the POC HbA1c were calculated. The factors associated with the difference in HbA1c and the association between POC HbA1c result and subsequent attendance of the NHS DPP were also evaluated.

Results

Data from 73 703 participants demonstrated a significant mean difference between the referral and POC HbA1c of −2.48 mmol/mol (−0.23%) (t=157, p<0.001) with significant differences in the mean difference between devices (F(2, 73 700)=738, p<0.001). The SD of POC HbA1c was 4.46 mmol/mol (0.41%) with significant differences in SDs between devices (F(2, 73 700)=1542, p<0.001). Participants who were older, from more deprived areas and from Asian, black and mixed ethnic groups were associated with smaller HbA1c differences. Normoglycemic POC HbA1c versus NDH POC HbA1c values were associated with lower subsequent attendance at behavioral interventions (58% vs 67%, p<0.001).

Conclusion

POC HbA1c testing in community settings was associated with significantly lower HbA1c values when compared with laboratory-measured referrals. Acknowledging effects of regression to the mean, we found that these differences were also associated with POC method, location, individual patient factors and time between measurements. Compared with POC HbA1c values in the NDH range, normoglycemic POC HbA1c values were associated with lower subsequent intervention attendance.
Acute and chronic neuroinflammation is triggered by diabetic ketoacidosis in a rat model
Authors: Glaser Nicole , Chu Steven , Hung Benjamin , Fernandez Luis , Wulff Heike , Tancredi Daniel , ODonnell Martha E
Published: March 2023

Introduction

Cognitive decline is common in patients with type 1 diabetes and has been attributed to the effects of chronic hyperglycemia and severe hypoglycemia. Diabetic ketoacidosis (DKA) has only recently been suspected to be involved in causing cognitive decline. We hypothesized that DKA triggers both acute and chronic neuroinflammation, contributing to brain injury.

Research methods and design

We measured concentrations of cytokines, chemokines and matrix metalloproteinases (MMP) in serum and brain tissue lysates in juvenile rats during and after DKA (during acute DKA, 24 hours and 7 days after DKA), and compared these to healthy controls and hyperglycemic controls. We also measured cytokine, chemokine and MMP concentrations in serum and brain tissue of adult rats (70 days) that had experienced DKA as juveniles and compared these measurements to those of adult diabetic rats without exposure to DKA.

Results

During acute DKA in the juvenile rats, serum concentrations of CCL3, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and MMP-9 were significantly increased. Serum concentrations of IL-2 and IL-17A increased 7 days after DKA recovery. In brain tissue lysates, concentrations of CCL3, CCL5, interferon (IFN)-γ and MMP-9 were significantly elevated during acute DKA. In adult rats that had DKA as juveniles (28 days previously), serum concentrations of IL-1ß and brain concentrations of IL-10 and IL-12p70 were elevated in comparison to diabetic rats without prior DKA. Composite scores for highly correlated cytokines and chemokines (mean z-scores for IL-10, IL-1ß, TNF-α, IL-17A, IFN-γ, CXCL-1 and CCL5) were also significantly elevated in adult rats with prior DKA.

Conclusions

These data confirm that DKA causes acute systemic inflammation and neuroinflammation in a rat model. Importantly, the neuroinflammatory response triggered by DKA is long-lasting, suggesting the possibility that DKA-induced chronic neuroinflammation could contribute to long-term cognitive decline in individuals with diabetes.
Common mental health and emotional and behavioural disorders among adolescents and young adults in Harare and Mashonaland East, Zimbabwe: a population-based prevalence study
Authors: Doyle Aoife Margaret , Bandason T , Dauya E , McHugh Grace , Grundy Chris , Simms Victoria , Chibanda D , Ferrand Rashida
Published: March 2023

Objectives

To estimate the prevalence of common mental health disorders (CMDs) and emotional and behavioural disorders among young people and to explore the correlates of CMDs risk.

Setting

Five urban and periurban communities in Harare and Mashonaland East, Zimbabwe

Design

Population-based cross-sectional study

Participants

Young people aged 13–24 years living in households in the study areas.

Outcome measures

The primary outcome was the proportion of participants screening positive for probable CMDs defined as a Shona Symptoms Questionnaire (SSQ) score ≥8. Secondary outcomes were emotional and behavioural disorders measured using the Strength and Difficulties Questionnaire (SDQ), and adjusted ORs for factors associated with CMD.

Results

Out of 634 young people, 37.4% (95% CI 33.0% to 42.0%) screened positive for probable CMDs, 9.8% (95% CI 7.5% to 12.7%) reported perceptual symptoms and 11.2% (95% CI 9.0% to 13.8%) reported suicidal ideation. Using UK norms to define normal, borderline and abnormal scores for each of the SDQ domains, a high proportion (15.8%) of Zimbabwean young people had abnormal scores for emotional symptoms and a low proportion had abnormal scores for hyperactivity/inattention scores (2.8%) and prosocial scores (7.1%). We created local cut-offs for the emotional symptoms, hyperactivity/attention and prosocial SDQ domains. The odds of probable CMDs increased with each year of age (OR 1.09, p<0.001) and was higher among those who were out of school and not working compared with those in school or working (adj. OR 1.67 (1.07, 2.62), p=0.04). One in five participants (22.1%) were referred immediately for further clinical assessment but uptake of referral services was low.

Conclusions

We observed a high prevalence of symptoms of CMDs among general population urban and peri-urban young people especially among those with no employment. There is a need for more accessible and acceptable youth-friendly mental health services.
Partner alcohol consumption and intimate partner violence among women in Papua New Guinea: a cross-sectional analysis of Demographic and Health Survey
Authors: Cadri Abdul , Aboagye Richard Gyan , Boadu Frimpong James , Yeboah Paa Akonor , Seidu Abdul-Aziz , Ahinkorah Bright Opoku
Published: March 2023

Objective

We examined the association between partner alcohol consumption and the experience of intimate partner violence among women in Papua New Guinea.

Design

We performed a cross-sectional analyses of data extracted from the 2016–2018 Papua New Guinea Demographic and Health Survey. We included 3319 women in sexual unions. Multilevel binary logistic regression analysis was used to examine the association between partner alcohol consumption and intimate partner violence, controlling for the covariates. Results from the regression analysis were presented using the crude odds ratios (cORs) and adjusted odds ratios (aORs), with 95% confidence intervals (CIs).

Setting

Papua New Guinea.

Participants

Women aged 15–49 years in sexual unions.

Outcome measures

Physical, emotional, and sexual violence.

Results

The prevalence of physical, emotional and sexual violence among women in sexual unions in Papua New Guinea were 45.9% (42.4 to 47.7), 45.1% (43.4 to 46.8) and 24.3% (22.9 to 25.8), respectively. The level of partner alcohol consumption was 57.3%. Women whose partners consumed alcohol were more likely to experience physical violence (aOR=2.86, 95% CI=2.43 to 3.37), emotional violence (aOR=2.89, 95% CI=2.44 to 3.43) and sexual violence (aOR=2.56, 95% CI=2.08 to 3.16) compared with those whose partners did not consume alcohol.

Conclusion

This study found a relatively high prevalence of intimate partner violence among women in Papua New Guinea. Most importantly, this study found partner alcohol consumption to be significantly and positively associated with intimate partner violence. The study, therefore, recommends that interventions seeking to reduce intimate partner violence among women in Papua New Guinea should intensify behaviour change and education on reducing or eliminating partner alcohol consumption.
Strategies, challenges and opportunities in the implementation of COVID-19 field hospitals: a scoping review
Authors: Hamis Amy Azira , Md Bukhori Ayuzeity Bistari , Heng Pei Pei , Jane Ling Miaw Yn , Shaharuddin Muhammad Al-Amin , A Fauzi Nazmeen Adline Fawwazah , Masdor Noor Azreen , Othman Rahayu , Ismail Aniza
Published: March 2023

Objectives

COVID-19 has strained healthcare systems, requiring the redesign of their structure, human resource management and clinical approach. Countries have adopted implementation strategies and maximise field hospital functionality to address the issue of overflow of patients with COVID-19. This scoping review was based on the main research question, ‘What are the implementation strategies, challenges and opportunities in managing the field hospital during the COVID-19 pandemic?’, and aimed to consolidate all recent evidence on COVID-19 field hospital implementation approaches, challenges and potentialities.

Design

Scoping review, following the Arksey and O’Malley’s framework, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines.

Data sources

PubMed, Web of Science and Scopus were searched from 1 January 2020 through 31 December 2021.

Eligibility criteria

Original articles, reviews, case studies and reports written in English were included. Works without full article and articles that did not answer the research questions were excluded.

Data extraction and synthesis

Data were extracted using a standardised data extraction form in Microsoft Excel. The findings of all included articles were synthesised narratively.

Results

Eighty-five records were reviewed and 25 studies were included. For the field hospital implementation strategies, ‘surge capacity’, namely space, human resource, supply and system, was discussed in addition to the preparation and workflow of other services such as pharmacy, rehabilitation, food and nutrition. The management of COVID-19 field hospitals is challenging with respect to staff and resource shortages, inability to anticipate patient load and poor communication. The opportunities and recommendations for improvement of management were also highlighted.

Conclusions

The compilation of lessons learnt may help improve the future management of field hospitals, administratively and clinically.
Comprehensive molecular phenotyping ofARID1A-deficient gastric cancer reveals pervasive epigenomic reprogramming and therapeutic opportunities
Authors: Xu Chang , Huang Kie Kyon , Law Jia Hao , Chua Joy Shijia , Sheng Taotao , Flores Natasha M , Pizzi Melissa Pool , Okabe Atsushi , Tan Angie Lay Keng , Zhu Feng , Kumar Vikrant , Lu Xiaoyin , Benitez Ana Morales , Lian Benedict Shi Xiang , Ma Haoran , Ho Shamaine Wei Ting , Ramnarayanan Kalpana , Anene-Nzelu Chukwuemeka George , Razavi-Mohseni Milad , Abdul Ghani Siti Aishah Binte , Tay Su Ting , Ong Xuewen , Lee Ming Hui , Guo Yu Amanda , Ashktorab Hassan , Smoot Duane , Li Shang , Skanderup Anders Jacobsen , Beer Michael A , Foo Roger Sik Yin , Wong Joel Shi Hao , Sanghvi Kaushal , Yong Wei Peng , Sundar Raghav , Kaneda Atsushi , Prabhakar Shyam , Mazur Pawel Karol , Ajani Jaffer A , Yeoh Khay Guan , So Jimmy Bok-Yan , Tan Patrick
Published: March 2023

Objective

Gastric cancer (GC) is a leading cause of cancer mortality, withARID1Abeing the second most frequently mutated driver gene in GC. We sought to decipherARID1A-specific GC regulatory networks and examine therapeutic vulnerabilities arising fromARID1Aloss.

Design

Genomic profiling of GC patients including a Singapore cohort (>200 patients) was performed to derive mutational signatures ofARID1Ainactivation across molecular subtypes. Single-cell transcriptomic profiles ofARID1A-mutated GCs were analysed to examine tumour microenvironmental changes arising fromARID1Aloss. Genome-wide ARID1A binding and chromatin profiles (H3K27ac, H3K4me3, H3K4me1, ATAC-seq) were generated to identify gastric-specific epigenetic landscapes regulated by ARID1A. Distinct cancer hallmarks ofARID1A-mutated GCs were converged at the genomic, single-cell and epigenomic level, and targeted by pharmacological inhibition.

Results

We observed prevalentARID1Ainactivation across GC molecular subtypes, with distinct mutational signatures and linked to a NFKB-driven proinflammatory tumour microenvironment.ARID1A-depletion caused loss of H3K27ac activation signals atARID1A-occupied distal enhancers, but unexpectedly gain of H3K27ac at ARID1A-occupied promoters in genes such asNFKB1andNFKB2. Promoter activation inARID1A-mutated GCs was associated with enhanced gene expression, increased BRD4 binding, and reduced HDAC1 and CTCF occupancy. Combined targeting of promoter activation and tumour inflammation via bromodomain and NFKB inhibitors confirmed therapeutic synergy specific toARID1A-genomic status.

Conclusion

Our results suggest a therapeutic strategy forARID1A-mutated GCs targeting both tumour-intrinsic (BRD4-assocatiated promoter activation) and extrinsic (NFKB immunomodulation) cancer phenotypes.
Rear-facing child safety seat effectiveness: evidence from motor vehicle crash data
Authors: Anderson D Mark , Peterson Ridge W
Published: March 2023

Introduction

In 2018, the American Academy of Pediatrics updated their car safety seat (CSS) guidelines to recommend that children ride rear-facing as long as possible, yet evidence from observational studies on rear-facing CSS effectiveness is limited. This study estimated the association between rear-facing CSS use and injuries among children aged 0–4 years who were involved in motor vehicle crashes (MVCs).

Methods

This study analysed data on all MVCs involving children aged 0–4 years reported to the Kansas Department of Transportation from 2011 to 2020. Children who were in a rear-facing CSS were compared with children who rode in a forward-facing device. Logistic regression was used to adjust for potential confounders.

Results

In unadjusted models, rear-facing CSS use was associated with a 14% reduction in the odds of suffering any injury versus riding in a forward-facing CSS (OR 0.860, 95% CI 0.805 to 0.919). In models adjusted for potential confounders, rear-facing CSS use was associated with a 9% reduction in the odds of any injury relative to riding forward-facing (OR 0.909, 95% CI 0.840 to 0.983). These estimates were driven by children seated in the back outboard positions. Rear-facing CSS use was also negatively associated with incapacitating/fatal injuries, but these estimates were imprecise.

Conclusions

Children aged 0–4 years are less likely to be injured in an MVC if they are restrained in a rear—as opposed to forward—facing CSS. These results are particularly relevant because a number of state CSS laws do not require children of any age to ride rear-facing.