bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of calcified right atrial myxoma extending into the inferior vena cava: a case report
Authors: Khan Mohammad Qaiser Aziz , Zaheer Amna , Yasir Sarib Bin , Fatima Ramsha , Anand Ayush
Published: October 2023

Cardiac myxomas can rarely involve the right atrium, get calcified and involve the inferior vena cava (IVC). Early surgical intervention is critical to prevent life-threatening complications. We presented the case of a 39-year-old male with fever, cough and shortness of breath for 1 week. Initial laboratory investigations revealed leucocytosis and thrombocytopenia. His electrocardiogram was normal, and his chest X-ray showed bilateral infiltrates. Based on the findings of a high-resolution chest computed tomography scan, echocardiography and cardiac magnetic resonance imaging, we made a provisional diagnosis of calcified right atrial myxoma extending up to the IVC. We managed the case with cardiopulmonary bypass via aortic cannulation followed by a right atriotomy. Post-operatively, the patient’s condition improved and was doing well on monthly follow-ups.
New transient ULX candidate in NGC 4254: evidence of circumbinary disc?
Authors: Allak Sinan
Published: October 2023

This paper presents the identification of a new transient ultraluminous X-ray source (ULX) candidate (ULX-3) with reaching a peak luminosity of ∼4 × 1039 erg s−1 in NGC 4254 by using archival Chandra, Swift/X-Ray Telescope, Hubble Space Telescope, and JWST observations. From precise astrometric calculations, unique optical, near-infrared, and mid-infrared counterparts were found. The spectral energy distribution (SED) and colour–magnitude diagrams of counterparts of the new ULX candidate were plotted to constrain the nature of the possible donor star. Evidence of a circumbinary disc was found from its SED with two blackbody temperatures of 1000 and 200 K. Moreover, according to the X-ray hardness ratios, ULX-3 exhibits very hard to very soft transitions as seen in some high-mass X-ray binaries with Be-star donors. Moreover, ULX-3 varies by more than two orders of magnitude in the 0.3–10 keV energy band as seen in typical transient ULXs.
New insights on ν–DM interactions
Authors: Brax Philippe , van de Bruck Carsten , Valentino Eleonora Di , Giaré William , Trojanowski Sebastian
Published: October 2023

We revisit the possibility of using cosmological observations to constrain models that involve interactions between neutrinos and dark matter. We show that small-scale measurements of the cosmic microwave background (CMB) with a few per cent accuracy are critical to uncover unique signatures from models with tiny couplings that would require a much higher sensitivity at lower multipoles, such as those probed by the Planck satellite. We analyse the high-multipole data released by the Atacama Cosmology Telescope, both independently and in combination with Planck and baryon acoustic oscillation measurements, finding a compelling preference for a non-vanishing coupling, $\log _{10}u_{\nu \textrm {DM}}=-5.20^{+1.2}_{-0.74}$ at 68 per cent confidence level. This aligns with other CMB-independent probes, such as Lyman-α. We illustrate how this coupling could be accounted for in the presence of dark matter interactions with a sterile neutrino.
Elevated A-to-I RNA editing in COVID-19 infected individuals
Authors: Merdler-Rabinowicz Rona , Gorelik David , Park Jiwoon , Meydan Cem , Foox Jonathan , Karmon Miriam , Roth Hillel S , Cohen-Fultheim Roni , Shohat-ophir Galit , Eisenberg Eli , Ruppin Eytan , Mason Christopher E , Levanon Erez Y
Published: October 2023

Given the current status of coronavirus disease 2019 (COVID-19) as a global pandemic, it is of high priority to gain a deeper understanding of the disease's development and how the virus impacts its host. Adenosine (A)-to-Inosine (I) RNA editing is a post-transcriptional modification, catalyzed by the ADAR family of enzymes, that can be considered part of the inherent cellular defense mechanism as it affects the innate immune response in a complex manner. It was previously reported that various viruses could interact with the host's ADAR enzymes, resulting in epigenetic changes both to the virus and the host. Here, we analyze RNA-seq of nasopharyngeal swab specimens as well as whole-blood samples of COVID-19 infected individuals and show a significant elevation in the global RNA editing activity in COVID-19 compared to healthy controls. We also detect specific coding sites that exhibit higher editing activity. We further show that the increment in editing activity during the disease is temporary and returns to baseline shortly after the symptomatic period. These significant epigenetic changes may contribute to the immune system response and affect adverse outcomes seen in post-viral cases.
Pathogenic signal peptide variants in the human genome
Authors: Gutierrez Guarnizo Sneider Alexander , Kellogg Morgana K , Miller Sarah C , Tikhonova Elena B , Karamysheva Zemfira N , Karamyshev Andrey L
Published: October 2023

Secreted and membrane proteins represent a third of all cellular proteins and contain N-terminal signal peptides that are required for protein targeting to endoplasmic reticulum (ER). Mutations in signal peptides affect protein targeting, translocation, processing, and stability, and are associated with human diseases. However, only a few of them have been identified or characterized. In this report, we identified pathogenic signal peptide variants across the human genome using bioinformatic analyses and predicted the molecular mechanisms of their pathology. We recovered more than 65 thousand signal peptide mutations, over 11 thousand we classified as pathogenic, and proposed framework for distinction of their molecular mechanisms. The pathogenic mutations affect over 3.3 thousand genes coding for secreted and membrane proteins. Most pathogenic mutations alter the signal peptide hydrophobic core, a critical recognition region for the signal recognition particle, potentially activating the Regulation of Aberrant Protein Production (RAPP) quality control and specific mRNA degradation. The remaining pathogenic variants (about 25%) alter either the N-terminal region or signal peptidase processing site that can result in translocation deficiencies at the ER membrane or inhibit protein processing. This work provides a conceptual framework for the identification of mutations across the genome and their connection with human disease.
Radiomic features define risk and are linked to DNA methylation attributes in primary CNS lymphoma
Authors: Nenning Karl-Heinz , Gesperger Johanna , Furtner Julia , Nemc Amelie , Roetzer-Pejrimovsky Thomas , Choi Seung-Won , Mitter Christian , Leber Stefan L , Hofmanninger Johannes , Klughammer Johanna , Ergüner Bekir , Bauer Marlies , Brada Martina , Chong Kyuha , Brandner-Kokalj Tanisa , Freyschlag Christian F , Grams Astrid , Haybaeck Johannes , Hoenigschnabl Selma , Hoffermann Markus , Iglseder Sarah , Kiesel Barbara , Kitzwoegerer Melitta , Kleindienst Waltraud , Marhold Franz , Moser Patrizia , Oberndorfer Stefan , Pinggera Daniel , Scheichel Florian , Sherif Camillo , Stockhammer Guenther , Stultschnig Martin , Thomé Claudius , Trenkler Johannes , Urbanic-Purkart Tadeja , Weis Serge , Widhalm Georg , Wuertz Franz , Preusser Matthias , Baumann Bernhard , Simonitsch-Klupp Ingrid , Nam Do-Hyun , Bock Christoph , Langs Georg , Woehrer Adelheid
Published: October 2023

Background

The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification.

Methods

In this retrospective study, we investigated 133 patients across 9 sites in Austria (2005–2018) and an external validation site in South Korea (44 patients, 2013–2016). We used T1-weighted contrast-enhanced MRI and an L1-norm regularized Cox proportional hazard model to derive a radiomic risk score. We integrated radiomic features with DNA methylation profiles using machine learning-based prediction, and validated the most relevant biological associations in tissues and cell lines.

Results

The radiomic risk score, consisting of 20 mostly textural features, was a strong and independent predictor of survival (multivariate hazard ratio = 6.56 [3.64–11.81]) that remained valid in the external validation cohort. Radiomic features captured gene regulatory differences such as in BCL6 binding activity, which was put forth as testable treatment target for a subset of patients.

Conclusions

The radiomic risk score was a robust and complementary predictor of survival and reflected characteristics in underlying DNA methylation patterns. Leveraging imaging phenotypes to assess risk and inform epigenetic treatment targets provides a concept on which to advance prognostic modeling and precision therapy for this aggressive cancer.
Utilizing Ceftazidime/Avibactam Therapeutic Drug Monitoring in the Treatment of Neurosurgical Meningitis Caused by Difficult-to-Treat Resistant Pseudomonas aeruginosa and KPC-Producing Enterobacterales
Authors: Yasmin Mohamad , Nutman Amir , Wang Lu , Marshall Steven , Chen Ke , Wang Jiping , Yahav Dafna , Lupinsky Liad , Hujer Andrea M , Bhimraj Adarsh , van Duin David , Li Jian , Bonomo Robert A
Published: October 2023

Background

Central nervous system (CNS) infections caused by Klebsiella pneumoniae carbapenemase (KPC)–producing Enterobacterales and difficult-to-treat resistant (DTR) Pseudomonas aeruginosa represent a formidable clinical challenge. Antimicrobial regimens that efficiently penetrate the cerebrospinal fluid (CSF) and achieve sufficient concentrations associated with microbiologic and clinical cure are limited. We evaluated therapy with ceftazidime-avibactam (CAZ-AVI) in order to guide precise dosing in the treatment of CNS infections.

Methods

Therapeutic drug monitoring (TDM) was performed in 3 patients with health care–associated ventriculitis and meningitis (HAVM) using CAZ-AVI 2.5 g infused intravenously every 8 hours as standard and extended infusion. Simultaneous CSF and plasma samples were obtained throughout the dosing interval in each patient. Concentrations of CAZ and AVI were determined by liquid chromatography/mass spectrometry.

Results

Bacterial identification revealed KPC-producing Klebsiella pneumoniae (KPC-Kp), DTR Pseudomonas aeruginosa, and KPC-producing Enterobacter cloacae (KPC-Ent.c). All isolates were resistant to carbapenems. The minimum inhibitory concentrations (MICs) of CAZ-AVI were 0.25/4, 4/4, and 0.25/4 μg/mL, respectively. CAZ and AVI concentrations were determined in CSF samples ranging from 29.0 to 15.0 µg/mL (CAZ component) and 4.20 to 0.92 µg/mL (AVI component), respectively. AVI achieved concentrations ≥1 µg/mL in 11 out of 12 CSF samples collected throughout the dosing interval. Clinical and microbiologic cure were attained in all patients.

Conclusions

Postinfusion concentrations of CAZ-AVI were measured in plasma and CSF samples obtained from 3 patients with complicated CNS infections caused by antimicrobial-resistant isolates. The measured concentrations revealed that standard CAZ and AVI exposures sufficiently attained values correlating to 50% fT > MIC, which are associated with efficient bacterial killing.
A comparative study of three modes of s-process nucleosynthesis in extremely metal-poor AGB stars
Authors: Yamada Shimako , Suda Takuma , Komiya Yutaka , Aikawa Masayuki , Fujimoto Masayuki Y
Published: October 2023

Carbon-enhanced metal-poor (CEMP) stars in the Galactic halo have a wide range of neutron-capture element abundance patterns. To identify their origin, we investigate three modes of s-process nucleosynthesis that have been proposed to operate in extremely metal-poor asymptotic giant branch (AGB) stars: convective 13C burning, which occurs when hydrogen is engulfed by helium-flash convection in low-mass AGB stars; convective 22Ne burning, which occurs in helium-flash convection of intermediate-mass AGB stars; and radiative 13C burning, which occurs in the 13C pocket that is formed during inter-pulse periods. We show that the production of s-process elements per iron seed (s-process efficiency) does not depend on metallicity below [Fe$/$H] = −2, because 16O in the helium zone dominates the neutron poison. The convective 13C mode can produce a variety of s-process efficiencies for Sr, Ba, and Pb, including the maxima observed among CEMP stars. The 22Ne mode only produces the lowest end of s-process efficiencies among CEMP models. We show that the combination of these two modes can explain the full range of observed enrichment of s-process elements in CEMP stars. In contrast, the 13C pocket mode can hardly explain the high level of enrichment observed in some CEMP stars, even if considering star-to-star variations of the mass of the 13C pocket. These results provide a basis for discussing the binary mass transfer origin of CEMP stars and their subgroups.
The NLR immune receptor ADR1 and lipase-like proteins EDS1 and PAD4 mediate stomatal immunity in Nicotiana benthamiana and Arabidopsis
Authors: Wang Hanling , Song Susheng , Gao Shang , Yu Qiangsheng , Zhang Haibo , Cui Xiulin , Fan Jun , Xin Xiufang , Liu Yule , Staskawicz Brian , Qi Tiancong
Published: October 2023

In the presence of pathogenic bacteria, plants close their stomata to prevent pathogen entry. Intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors recognize pathogenic effectors and activate effector-triggered immune responses. However, the regulatory and molecular mechanisms of stomatal immunity involving NLR immune receptors are unknown. Here, we show that the Nicotiana benthamiana RPW8-NLR central immune receptor ACTIVATED DISEASE RESISTANCE 1 (NbADR1), together with the key immune proteins ENHANCED DISEASE SUSCEPTIBILITY 1 (NbEDS1) and PHYTOALEXIN DEFICIENT 4 (NbPAD4), plays an essential role in bacterial pathogen- and flg22-induced stomatal immunity by regulating the expression of salicylic acid (SA) and abscisic acid (ABA) biosynthesis or response-related genes. NbADR1 recruits NbEDS1 and NbPAD4 in stomata to form a stomatal immune response complex. The transcription factor NbWRKY40e, in association with NbEDS1 and NbPAD4, modulates the expression of SA and ABA biosynthesis or response-related genes to influence stomatal immunity. NbADR1, NbEDS1, and NbPAD4 are required for the pathogen infection-enhanced binding of NbWRKY40e to the ISOCHORISMATE SYNTHASE 1 promoter. Moreover, the ADR1-EDS1-PAD4 module regulates stomatal immunity in Arabidopsis (Arabidopsis thaliana). Collectively, our findings show the pivotal role of the core intracellular immune receptor module ADR1-EDS1-PAD4 in stomatal immunity, which enables plants to limit pathogen entry.
Did California Act to Save Lives? AB 392 and fatal officer-involved shootings
Authors: Powell Zachary A
Published: October 2023

American police face considerable criticism from the public about the perceived unnecessary and excessive use of deadly force in civilian interactions. Police reform advocates often call for widespread change to reduce officer-involved shootings and other forms of deadly force. Some, such as California, pursued statewide legal interventions to limit police deadly force. AB 392, the California Act to Save Lives, changed the deadly force standard so that objectively reasonable officers, when considering the totality of circumstances, can only use deadly force when necessary to defend human life. The stricter standard was designed to limit officer deadly force and reduce civilian deaths so this paper considers the efficacy of AB 392 on the incidence of fatal force in California. The results of interrupted time series and synthetic control method (SCM) analyses find no evidence of a reduction in deadly force after the passage of AB 392. Any effort to change deadly force should be coupled with legislative changes and evidence-based practices. Policymakers, practitioners, and researchers will need to explore a multi-pronged approach to reduce deadly force encounters.
Potential effects of spirulina and date palm pollens on zinc oxide nanoparticles -induced hepatoxicity, oxidative stress, and inflammation in male albino rats
Authors: Al-Azhary Diaa B , Sawy Samar A , Fawzy Hassan Hanaa , Meligi Noha M
Published: October 2023

Introduction: The application of Zinc oxide nanoparticles (ZnO NPs) is substantially growing in industrial products. Therefore, humans are increasingly exposed to ZnO NPs daily due to their extensive range of applications, raising worries about their possible toxicity. Aim: In this study, the ameliorative effects of raw Phoenix dactylifera L. (date palm) pollens (DPP) and Spirulina platensis (SP) independently against ZnO NPS-induced hepatoxicity in male albino rats were examined. Methods: Six groups (6/group) of adult male albino rats received oral treatment using distilled water (control), SP (1000 mg/kg b. wt.), DPP (100 mg/kg b. wt.), ZnO NPs (100 mg/kg b. wt.), ZnO NPs +SP, and ZnO NPs + DPP respectively for 15 days. Results: The results of the biochemical investigation indicated that the administration of ZnO NPs substantially upregulated (p < 0.05) transaminases, alkaline phosphatase, and bilirubin serum levels. Malondialdehyde and pro-inflammatory cytokine serum levels were also elevated after ZnO NPs administration. Simultaneously, the downregulated catalase and glutathione peroxidase serum activities were significantly suppressed in ZnO NPs treated rats. Moreover, exposure to ZnO NPs induced liver histopathological alterations. The administration of SP and DPP ameliorated the aforementioned effects caused by ZnO NPs. This result can be attributable to the downregulation of hepatic transaminases, alkaline phosphatase, and bilirubin in the serum and the antioxidation system's equilibration, thus alleviating the accumulation of reactive oxygen species. Conclusion: SP and DPP are natural antioxidants with the potential to eliminate inflammation as well as oxidative damage caused by ZnO NPs in hepatic tissue.
Identification of Meloidogyne Species on Traditional Chinese Medicine Plants in the Qinling Mountain Area of China and Their Aggressiveness to Different Medicinal Herbs
Authors: Pan Song , Wei Peiyao , Li Yu , Chen Zhijie , Peng Deliang , Wang Li , Liu Chen , Hong Bo , Zhang Feng , Li Yingmei
Published: October 2023

Root-knot nematodes (Meloidogyne spp.) are plant-parasitic nematodes that cause serious damage worldwide. There are many species of traditional Chinese medicine (TCM) plants, but only a few have been reported to be infected by Meloidogyne species. From 2020 to 2022, a survey was conducted in the Qinling mountain area, which is the main production region of TCM plants in China. Obvious galling symptoms were observed on the root systems of 15 species of TCM plants. Females were collected from diverse diseased TCM plants and subsequently identified at morphological and molecular levels. Among the 20 diseased root samples collected, Meloidogyne hapla populations were identified in 12 samples (60%), and M. incognita populations were identified in eight samples (40%). Among the 15 species of diseased TCM plants, eight species, namely, Scutellaria baicalensis, Leonurus japonicus, Dioscorea zingiberensis, Cornus officinalis, Viola philippica, Achyranthes bidentata, Senecio scandens, and Plantago depressa, were reported to be infected by Meloidogyne species for the first time. The host status of five species of TCM plants for two M. hapla isolates and one M. incognita isolate from TCM plants in this study was then evaluated. Differences in TCM plants’ response to nematode infection were apparent when susceptibility was evaluated by the egg counts per gram of fresh root and the reproduction factor of the nematodes. Among the five species of TCM plants tested, Salvia miltiorrhiza and Gynostemma pentaphyllum were the most susceptible, while S. baicalensis and V. philippica were not considered suitable hosts for M. hapla or M. incognita.
The Effect of Reiki and Aromatherapy on Vital Signs, Oxygen Saturation, and Anxiety Level in Patients Undergoing Upper Gastrointestinal Endoscopy
Authors: Keşer Esra , Bağlama Sevgin Samancıoğlu , Sezer Cem
Published: October 2023

This randomized controlled study aimed to determine the effect of Reiki and aromatherapy on vital signs, oxygen saturation, and anxiety level in patients undergoing upper gastrointestinal endoscopy. The sample consisted of 100 patients divided into Reiki (n = 34), aromatherapy (n = 33), and control (n = 33) groups. Data were collected 3 times (before, during, and after the procedure) using a descriptive characteristics questionnaire, a follow-up form, and the State Anxiety Subscale. The Reiki group had a mean State Anxiety Subscale score of 53.59 ± 2.98 and 43.94 ± 4.31 before and after the procedure, respectively. The aromatherapy group had a mean State Anxiety Subscale score of 54.03 ± 4.03 and 43.85 ± 3.91 before and after the procedure, respectively. The control group had a mean State Anxiety Subscale score of 38.79 ± 4.68 and 53.30 ± 7.26 before and after the procedure, respectively (P < .05). The results showed that the Reiki and aromatherapy groups had significantly lower State Anxiety Subscale scores than the control group after the procedure, indicating that Reiki and aromatherapy help reduce anxiety levels. There was a significant difference in the mean respiratory rates and oxygen saturation levels between the groups (P < .05). In conclusion, patients who do Reiki or undergo aromatherapy are less likely to experience anxiety before upper gastrointestinal endoscopy.
The Mechanisms of Luteolin in Treating COVID-19 Based on Bioinformatics Analysis and Molecular Docking
Authors: Rong Hechen , Zeng Yu , Zheng Nan , Wang Yiwei , Guo Zhonghong , Wang Kun , Huang Xiaoping
Published: October 2023

Luteolin is a natural flavonoid that has a variety of pharmacological activities, such as anti-inflammatory, anti-allergic, anti-bacterial, anti-viral, apoptosis inhibition, cell autophagy regulation, and anti-tumor activity. It is one of the main ingredients of an expert-recommended herbal formula for the prevention and treatment of coronavirus disease 2019 (COVID-19). This suggests that luteolin has strong pharmacological effects on the prevention and treatment of COVID-19. The aims of this study were to identify the molecular targets of luteolin and to infer the possible mechanisms by which it exerts its pharmacological effects. The GSE159787 data set was obtained from the Gene Expression Omnibus online database, and differentially expressed genes were analyzed. There were 22 upregulated differentially expressed genes enriched in the COVID-19 signaling pathway, suggesting that the upregulation of these genes may be closely related to the occurrence of COVID-19. Molecular docking results showed that luteolin had strong binding efficiency to 20 of these 22 key genes. Six of these genes (CFB, EIF2AK2, OAS1, MAPK11, OAS3, and STAT1) showed strong binding activity. Luteolin can regulate the COVID-19 signaling pathway by combining with these targets, which may have a therapeutic effect on COVID-19.
Nomogram for Predicting Viral Shedding Time of SARS-CoV-2 Delta Variant in Patients with COVID-19: A Retrospective Study
Authors: Zhou Jiejun , Fan Lin , Li Duo , Chen Mingwei , Yang Tian
Published: October 2023

Background

The coronavirus disease 2019 (COVID-19) cases continue to rise, and the demand for medical treatment and resources in healthcare systems surges. Assessing the viral shedding time (VST) of patients with COVID-19 can facilitate clinical decision making. Although some studies have been conducted on the factors affecting the VST of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), few prediction models are currently available.

Methods

This retrospective study included the consecutive patients with COVID-19 admitted to Xi’an Chest Hospital in Shaanxi, China, for treatment between December 19, 2021 and February 5, 2022. The clinical data of the patients were extracted from their electronic medical records. Combining significant factors affecting the VST, a nomogram was developed to predict the VST of the SARS-CoV-2 Delta variant in patients with COVID-19.

Results

We included 332 patients in this study. The average VST was 21 d. VST was significantly prolonged in patients with severe clinical symptoms, sore throat, old age, long time from onset to diagnosis, and an abnormal white blood cell count. Consequently, we developed a nomogram prediction model using these 5 variables. The concordance index (C-index) of this nomogram was 0.762, and after internal validation using bootstrapping (1000 resamples), the adjusted C-index was 0.762. The area under the nomogram’s receiver operator characteristic curve showed good discriminative ability (0.965). The calibration curve showed high consistency. The VST was prolonged in the group with lower model fitting scores according to the Kaplan-Meier curve (χ2=286, log-rank P < 0.001).

Conclusions

We developed a nomogram for predicting VST based on 5 easily accessible factors. It can effectively estimate the appropriate isolation period, control viral transmission, and optimize clinical strategies.
Recommend Guideline on Prevention of Mother-to-Child Transmission of HIV in China in 2020
Authors: Qu Shuiling , Wang Qian , Wang Xiaoyan , Qiao Yaping , Yao Jun , Li Zhen , Jin Xi , Li Zhixin , Wang Ailing
Published: October 2023

In China, a pilot project for the prevention of mother-to-child transmission (PMTCT) of the HIV was initiated in 2001. For the PMTCT of HIV, the Chinese government has released versions of the guidelines since 2004. In 2014, the World Health Organization released guidance on global processes and criteria for the validation of elimination of mother-to-child transmission of HIV and syphilis. To promote the elimination of mother-to-child transmission of HIV, syphilis, and hepatitis B virus in China, the Chinese government updated the Guideline for PMTCT of HIV, Syphilis, and Hepatitis B in 2020 (briefly as Guideline-2020). The Guideline-2020 comprises 5 parts: goals, interventions, support measures, duties and cooperation of departments, and definition indicators for PMTCT of HIV and corresponding calculation formulas. Compared with the previous versions, the key points updated in the Guideline-2020 are that the goals are set again, and health education and promotion, the procedure of HIV testing for pregnant women, and the antiretroviral therapy regimen for HIV-positive pregnant women and antiretroviral) prophylaxis regimen for infants are all updated. The antiretroviral prophylaxis regimen as zidovudine-lamivudine-nevirapine/lopinavir/ritonavir twice per day for 6 weeks is recommended for infants at high exposure risk to HIV, whereas the third antiretroviral therapy regimen as tenofovir-lamivudine-lopinavir/ritonavir is recommended for HIV-positive pregnant women, and indicators for PMTCT of HIV and corresponding calculation formulas are defined.
A 20-Year Study of Intracranial Pyogenic Complications of Sinusitis in Children
Authors: Smiljkovic Mina , Tat Jennifer , Richardson Susan E. , Campigotto Aaron , Cushing Sharon L. , Wolter Nikolaus E. , Dirks Peter , Bitnun Ari
Published: October 2023

Background:

Intracranial pyogenic complications of sinusitis in children can lead to serious sequelae. We characterize the clinical, epidemiologic and microbiologic characteristics of children with such complications over a 20-year period.

Methods:

Single-center retrospective chart review. Cases were identified based on International Classification of Diseases diagnostic codes (ICD)-9 and ICD-10 depending on the year and by reviewing all intracranial microbiologic samples.

Results:

A total of 104 cases of complicated sinusitis were included after review of 1591 charts. Median age was 12 (IQR 9–14); 72 were male (69%). The most frequent complications were epidural empyema (n = 50, 48%), subdural empyema (n = 46, 44%) and Pott’s puffy tumor (n = 27, 26%). 52% (n = 54) underwent neurosurgery and 46% (n = 48) underwent otolaryngologic surgery. The predominant pathogen isolated from sterile site specimens was Streptococcus anginosus (n = 40, 63%), but polymicrobial growth was common (n = 24; 38%). The median duration of intravenous antibiotic therapy was 51 days (IQR 42–80). Persistent neurologic sequelae (or death, n = 1) were found in 24% (n = 25) and were associated with the presence of cerebritis and extensive disease on neuroimaging (P = 0.02 and P = 0.04, respectively).

Conclusions:

Intracranial complications of sinusitis continue to cause significant morbidity in children. Polymicrobial infections are common, which reinforces the need for broad-spectrum empiric antibiotic therapy and cautious adjustment of the antibiotic regimen based primarily on sterile site cultures. The association of neurologic sequelae with the presence of cerebritis and extensive intracranial involvement on neuroimaging suggest that delayed diagnosis may be a contributor to adverse outcome.
Comparison of the analgesic effects of “superficial” and “deep” repetitive transcranial magnetic stimulation in patients with central neuropathic pain: a randomized sham-controlled multicenter international crossover study
Authors: Bouhassira Didier , Jazat-Poindessous Frédérique , Farnes Nadine , Franchisseur Claire , Stubhaug Audun , Bismuth Julie , Lefaucheur Jean-Pascal , Hansson Per , Attal Nadine
Published: October 2023

We directly compared the analgesic effects of “superficial” and ‘deep” repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex in patients with central neuropathic pain. Fifty-nine consecutive patients were randomly assigned to active or sham “superficial” (using a figure-of-8 [F8]-coil) or “deep” (using a Hesed [H]-coil) stimulation according to a double-blind crossover design. Each treatment period consisted of 5 daily stimulation sessions and 2 follow-up visits at 1 and 3 weeks after the last stimulation session. The primary outcome was the comparison of the mean change in average pain intensity over the course of the treatment (group × time interaction). Secondary outcomes included neuropathic symptoms (NPSI), pain interference, patient global impression of change (PGIC), anxiety, depression, and catastrophizing. In total, 51 patients participated in at least one session of both treatments. There was a significant interaction between “treatment” and “time” (F = 2.7; P = 0.0024), indicating that both figure-8 (F8-coil) and H-coil active stimulation induced significantly higher analgesic effects than sham stimulation. The analgesic effects of both types of coils had a similar magnitude but were only moderately correlated (r = 0.39, P = 0.02). The effects of F8-coil stimulation appeared earlier, whereas the effects of H-coil stimulation were delayed, but tended to last longer (up to 3 weeks) as regards to several secondary outcomes (PGIC and total NPSI score). In conclusion, “deep” and “superficial” rTMS induced analgesic effects of similar magnitude in patients with central pain, which may involve different mechanisms of action.
Efficacy and safety of eliapixant in diabetic neuropathic pain and prediction of placebo responders with an exploratory novel algorithm: results from the randomized controlled phase 2a PUCCINI study
Authors: Bouhassira Didier , Tesfaye Solomon , Sarkar Arnab , Soisalon-Soininen Sari , Stemper Brigitte , Baron Ralf
Published: October 2023

Phase 2a of the PUCCINI study was a placebo-controlled, double-blind, parallel-group, multicenter, proof-of-concept study evaluating the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with diabetic neuropathic pain (DNP) (ClinicalTrials.gov NCT04641273). Adults with type 1 or type 2 diabetes mellitus with painful distal symmetric sensorimotor neuropathy of >6 months' duration and neuropathic pain were enrolled and randomized 1:1 to 150 mg oral eliapixant twice daily or placebo for 8 weeks. The primary endpoint was change from baseline in weekly mean 24-hour average pain intensity score at week 8. In total, 135 participants completed treatment, 67 in the eliapixant group and 68 in the placebo group. At week 8, the change from baseline in posterior mean 24-hour average pain intensity score (90% credible interval) in the eliapixant group was −1.56 (−1.95, −1.18) compared with −2.17 (−2.54, −1.80) for the placebo group. The mean treatment difference was 0.60 (0.06, 1.14) in favor of placebo. The use of a model-based framework suggests that various factors may contribute to the placebo-responder profile. Adverse events were mostly mild or moderate in severity and occurred in 51% of the eliapixant group and 48% of the placebo group. As the primary endpoint was not met, the PUCCINI study was terminated after completion of phase 2a and did not proceed to phase 2b. In conclusion, selective P2X3 antagonism in patients with DNP did not translate to any relevant improvement in different pain intensity outcomes compared with placebo. Funding: Bayer AG.
Outcomes in Obese Adult Veno-Venous Extracorporeal Membrane Oxygenation: A Systematic Review
Authors: Reid Trista D. , Crespo Regalado Ricardo , Carlson Rebecca , Schneider Andrew , Boone Joshua S. , Hockran Sophie , Butler Logan R. , Perez Dakota L. , Holloway Alexa D. , Nguyen Phu G. , Gallaher Jared , Charles Anthony G. , Raff Lauren
Published: October 2023

Obesity is associated with an overall increased risk of morbidity and mortality. However, in patients with critical illness, sepsis, and acute respiratory distress syndrome, obesity may be protective, termed “the obesity paradox.” This is a systematic literature review of articles published from 2000 to 2022 evaluating complications and mortality in adults with respiratory failure on veno-venous extracorporeal membrane oxygenation (VV ECMO) based on body mass index (BMI). Eighteen studies with 517 patients were included. Common complications included acute renal failure (175/377, 46.4%), venous thrombosis (175/293, 59.7%), and bleeding (28/293, 9.6%). Of the six cohort studies, two showed improved mortality among obese patients, two showed a trend toward improved mortality, and two showed no difference. Comparing all patients in the studies with BMI of less than 30 to those with BMI of greater than or equal to 30, we noted decreased mortality with obesity (92, 37.1% of BMI <30 vs. 30, 11% of BMI ≥30, p ≤ 0.0001). Obesity may be protective against mortality in adult patients undergoing VV ECMO. Morbid and super morbid obesity should not be considered a contraindication to cannulation, with patients with BMI ≥ 80 surviving to discharge. Complications may be high, however, with higher rates of continuous renal replacement therapy and thrombosis among obese patients.
What is new in mediastinal staging?
Authors: Schwalk Audra J. , Niroula Abesh , Schimmel Matthew
Published: October 2023

Purpose of review

Appropriate staging is of utmost importance in nonsmall cell lung cancer (NSCLC), as the pathologic stage dictates both overall prognosis and appropriate therapeutic pathways. This article seeks to review the current recommendations for mediastinal staging of NSCLC and available modalities to achieve this. Landmark publications pertaining to recent advancements in NSCLC treatments are also highlighted and the role of specific bronchoscopic modalities for tissue acquisition are reviewed.

Recent findings

Recent advancements in the treatment of NSCLC have made accurate mediastinal staging more important than ever. Guidelines and recommendations outlining patients that warrant invasive mediastinal staging are available and a systematic approach should be utilized when sampling is performed. Ensuring the adequacy of tissue for the growing number of molecular biomarkers that must be tested has been the focus of many recent studies.

Appropriate mediastinal staging is crucial for the management of patients with NSCLC as is obtaining adequate tissue for diagnostic and therapeutic purposes. EBUS-TBNA is sufficient for the diagnosis of nonsmall cell and small cell lung carcinomas, but EBUS-guided intranodal forceps and cryobiopsy may provide more optimal specimen for patients with benign disease, such as sarcoidosis, or in cases of lymphoma. Further studies are necessary to better delineate the role of these techniques in the diagnosis and staging of mediastinal diseases before they become the primary diagnostic modalities.
Impact of junior doctor strikes on patient flow in the emergency department: a cross-sectional analysis
Authors: Ravioli Svenja , Jina Raeesa , Risk Omar , Cantle Fleur
Published: October 2023

Background and importance

Healthcare worker strikes are a global phenomenon. Mortality and morbidity seem to be unaffected by doctor strikes, but there is little evidence on the impact on emergency department (ED) flow and patient characteristics. In March and April 2023, two consecutive UK junior doctor strikes occurred.

Objectives

This study investigated the impact of junior doctor strikes on ED patient flow. Additionally, variation in patient presentations was compared between non-strike and strike days.

Design, setting and participants

This cross-sectional study was conducted at King’s College Hospital ED, a university hospital in London. All ED attendances during the 72- and 96-hour strike actions were compared with the corresponding non-strike days of the previous week.

Outcome measures and analysis

National key performance indicators (KPIs) were analysed and compared between non-strike and strike days. Patients’ demographics, acuity and diagnoses were compared. Outcome measures included number of 4-hour breaches, number of patients admitted or discharged and ED mortality. Staff seniority was categorised into levels for analysis.

Main results

There was increased ED patient flow during strike days with a significantly shorter total time in department in March [240 min (IQR 155–469) vs. 286 min (IQR 198.5–523.5), P < 0.001] and in April [222.5 min (IQR 147–351) vs. 251.5 min (IQR 174–443), P < 0.001]. Time to first clinician, treatment, and decision to admit were all shorter during both strike actions. Number of attendances, acuity, diagnoses, admission, discharge, and mortality rates were similar during strike and non-strike days. Staffing numbers were lower or equivalent on strike days but level of seniority was higher (P < 0.001).

Conclusion

The improved KPIs and increased patient flow during strike days, while multifactorial, seem largely attributed to the higher number of senior staff. Patient presentations and outcomes were unaffected by junior doctor strike action.
Traumatic injuries of the immature hip and pelvis
Authors: Moore David , Gnap Rose , Monsell Fergal
Published: October 2023

Purpose of review

The pelvis and hip account for 0.3--4% of fractures of the immature skeleton, and generally result from high energy trauma. These fractures range in severity from apophyseal avulsions to complete disruptions of the pelvic ring. The purpose of this article is to review the presentation, diagnosis, treatment and complications of these injuries in order to inform clinicians involved in their management. There is a lack of evidence-based management protocols for fractures of the immature pelvis largely due to their rarity and lack of robust scientific literature on the topic.

Recent findings

Computed tomography/MRI is essential as up to 30% of pelvis and 70% of acetabular fractures are not identified on initial radiographs. A sub-optimal outcome is common in unstable fractures treated conservatively and adequate reduction and surgical stabilization is often required to avoid long-term morbidity.

A coordinated approach involves resuscitation and temporary stabilization with planned definitive fixation. It is generally accepted that these injures should be managed in paediatric trauma centres. Whilst injuries vary in pattern and severity, we present an overview that considers the evaluation and treatment of the paediatric patient with pelvic and hip fractures to ensure that these injuries are identified promptly and treated by surgeons familiar with contemporary management algorithms.
Effectiveness of Nonpharmacologic Interventions for Chemotherapy-Induced Peripheral Neuropathy in Patients With Breast Cancer
Authors: Li Ruolin , Liu Yu , Xue Rui , Wang Ying , Zhao Fuyun , Chen Lu , Liu Jun-E
Published: October 2023

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in patients with breast cancer (BC) during treatment. Patients experiencing CIPN develop neuropathic symptoms, which could lead to the modification or discontinuation of chemotherapy. Nonpharmacological interventions can be simple and safe, but evidence of their effectiveness in patients with BC experiencing CIPN is currently insufficient.

Objective

To compare and rank the effectiveness of nonpharmacologic interventions for CIPN in patients with BC.

Methods

We conducted a systematic search of randomized controlled trials registered from database inception until October 2022 in 7 databases. We assessed studies that met the inclusion and exclusion criteria and evaluated the risk of bias. Network meta-analysis was conducted using Stata SE 17.0 (StataCorp, College Station, Texas).

Results

A total of 13 studies involving 9 nonpharmacologic interventions and comprising 571 participants were included. The results of the network meta-analysis showed that cryotherapy (standard mean difference, −1.22; 95% confidence interval, −2.26 to −0.17) exerted significant effects versus usual care. Cryotherapy (surface under the cumulative ranking area [SUCRA]: 0.74) was associated with the highest likelihood of effectively alleviating CIPN in patients with BC, followed by exercise (SUCRA: 0.62) and self-acupressure (SUCRA: 0.59).

Conclusions

Cryotherapy was the most effective nonpharmacologic intervention for alleviating CIPN in patients with BC. Large-scale studies are required to verify the present findings.

Implications for Practice

This study provides evidence regarding the effectiveness of nonpharmacologic interventions for CIPN. Physicians and nurses could incorporate cryotherapy into clinical practice to alleviate CIPN in patients with BC.
The Effectiveness and Safety of Nurse-Led Auricular Acupressure on Chemotherapy-Induced Peripheral Neuropathy Among Patients With Breast Cancer
Authors: Jung Mi Sook , Kim Mijung , Sohn Eun Hee , Lee Jin Sun
Published: October 2023

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a major symptom of distress among chemotherapy-treated cancer survivors. Although various interventions have been attempted, there is no criterion-standard treatment.

Objective

The aim of this study was to examine the efficacy and safety of auricular acupressure (AA) in improving peripheral neuropathy symptoms in breast cancer patients undergoing taxane-based treatment.

Methods

A total of 51 eligible participants were enrolled and randomly allocated (1:1) to AA or sham control groups. The intervention was performed weekly for 3 weeks using different ear points, depending on the group. The Total Neuropathy Score was used to measure CIPN objectively. The Numerical Rating Scale and the European Organization for Research and Treatment of Cancer Quality of Life Chemotherapy-Induced Peripheral Neuropathy-20 were used to measure the subjective symptoms of CIPN. Outcomes were compared between groups by time interaction using generalized estimating equations based on the intention-to-treat principle.

Results

Only 1 participant dropped out because of nausea and mild fever. The results of generalized estimating equations showed significant improvement in Numerical Rating Scale scores on the hands and feet and total Chemotherapy-Induced Peripheral Neuropathy-20 in the experimental group compared with the sham control group (all Ps < .05). Although the experimental group showed a greater reduction in Total Neuropathy Score scores than the sham control group, no significant differences were found.

Conclusion

Auricular acupressure is an effective and safe nurse-led intervention for managing CIPN symptoms in breast cancer patients.

Implications for Practice

The findings help nurses to integrate AA easily and usefully into nursing care, contributing to managing symptoms of CIPN in cancer patients and survivors.
Aligning Simulation-Based Education With Didactic Learning in Prelicensure Baccalaureate Nursing Education
Authors: Weeks Karen , Herron Elizabeth , Buchanan Holly
Published: October 2023

Background:

Research has shown there is a gap between academia and practice. Nursing stakeholders support the use of the clinical judgment model in developing competency for practice.

Purpose:

This study analyzed the effectiveness of simulation-based education on the development of clinical judgment and explored new graduate nurses' perceptions of their preparation for practice.

Methods:

A longitudinal, explanatory, mixed-methods design with survey points at onset and end of the intervention and interviews 6 months postgraduation.

Results:

The Simulation Effectiveness Tool-Modified (SET-M) was utilized for the pre- and posttest surveys. Two-tailed Mann-Whitney 2-sample rank sum tests were conducted and analyzed for all items on the SET-M. Significant differences were seen in pre- and posttest responses for 12 of the 19 SET-M survey items.

Conclusion:

The findings of this study support the deliberate alignment of didactic and practical teaching strategies to strengthen practice performance and bridge the gap.
Trigeminal neuropathy presenting secondary to SARS-CoV-2 infection
Authors: O'Neill Francis , De Stefano Gianfranco , Pridgeon Mike , Bhargava Deepti , Marshall Anne , Marshall Andrew , Frank Bernhard
Published: October 2023

Introduction:

A 58-year-old woman presented to a multidisciplinary facial pain clinic in October 2021 complaining of a constant pain in the right side of her face since contracting coronavirus SARS-CoV-2 18 months earlier. The pain extending from the right temple down to her right cheek extraorally and including the maxillary teeth and right side of tongue intraorally. This was accompanied by anosmia, diplopia on lateral gaze, and dizziness.

Methods:

Clinical examination was supplemented with several neurophysiological tests to confirm the diagnosis including an MRI brain scan, quantitative sensory testing, electrophysiological blink reflex testing, corneal confocal microscopy, and pain and short-form anxiety and depression questionnaires.

Results:

Quantitative sensory testing showed unilateral loss of perception in thermal and mechanical sensibility and bilateral hyperalgesia indicating central sensitization. Bilateral corneal confocal microscopy showed an abnormally reduced corneal nerve fibre length on the right side. MRI, blink reflex, and masseter inhibitory testing findings were normal.

Conclusion:

This case study is the first case of trigeminal neuropathy related to SARS-CoV-2 infection reported in the literature. It also discusses the successful management of the patient's trigeminal neuropathic pain.