bluuebunny/crossref_metadata_2025 huggingface dataset:
Catalyst-free biphasic orthorhombic/hexagonal tungsten oxide system with enhanced photocatalytic response under visible light
Authors: Singh Anshu Kumar , Pandey Sumit Kumar , Vishwakarma Pramod Kumar , Pratap Raghvendra , Verma Ranjana , Pandey Anamika , Giri Rajiv , Srivastava Anchal
Published: May 2023

These days, textile industries pose a more significant threat to surface water and groundwater sources directly or indirectly by discharging wastewater containing various dyes and organic pollutants to these water sources. The phase-junction-engineered heterogeneous photocatalysis carried out by visible light-driven semiconductor photocatalysts is opening a new window for the degradation of environmental organic pollutants. In this work, we have reported a one-step bottom-up hydrothermal synthesis of biphasic tungsten oxide (o/h-WO3) and performed a photodegradation experiment under visible light irradiation for the efficient degradation of organic pollutants such as Methylene blue (MB) and Methyl violet (MV), respectively. The X-ray diffraction, RAMAN, transmission electron microscopy and ultraviolet–Vis characterization techniques were used to investigate the structural, morphological and optical properties of the as-synthesized o/h-WO3. Moreover, the low calculated band gap (∼2.8 eV) and the anionic nature of o/h-WO3 suggest it as an efficient visible light-driven photocatalyst suitable for heterogeneous photocatalysis. The photodegradation experiment performed under visible light using o/h-WO3 photocatalyst showed better degradation efficiency of 71% and 89% for MB and MV, respectively, in 100 min. The dyes followed first-order kinetics, and their kinetic rate constants were calculated using the Langmuir–Hinshelwood model. Furthermore, the recyclability study of the photocatalyst was also performed and discussed the underlying mechanism for the photodegradation of the organic dyes.
Lysosomal Ca2+ flux modulates automaticity in ventricular cardiomyocytes and correlates with arrhythmic risk
Authors: Xie An , Kang Gyeoung-Jin , Kim Eun Ji , Feng Feng , Givens Sophie E , Ogle Brenda M , Dudley Samuel C
Published: May 2023

Automaticity involves Ca2+ handling at the cell membrane and sarcoplasmic reticulum (SR). Abnormal or acquired automaticity is thought to initiate ventricular arrhythmias associated with myocardial ischemia. Ca2+ flux from mitochondria can influence automaticity, and lysosomes also release Ca2+. Therefore, we tested whether lysosomal Ca2+ flux could influence automaticity. We studied ventricular human-induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs), hiPSC 3D engineered heart tissues (EHTs), and ventricular cardiomyocytes isolated from infarcted mice. Preventing lysosomal Ca2+ cycling reduced automaticity in hiPSC-CMs. Consistent with a lysosomal role in automaticity, activating the transient receptor potential mucolipin channel (TRPML1) enhanced automaticity, and two channel antagonists reduced spontaneous activity. Activation or inhibition of lysosomal transcription factor EB (TFEB) increased or decreased total lysosomes and automaticity, respectively. In adult ischemic cardiomyocytes and hiPSC 3D EHTs, reducing lysosomal Ca2+ release also inhibited automaticity. Finally, TRPML1 was up-regulated in cardiomyopathic patients with ventricular tachycardia (VT) compared with those without VT. In summary, lysosomal Ca2+ handling modulates abnormal automaticity, and reducing lysosomal Ca2+ release may be a clinical strategy for preventing ventricular arrhythmias.
Outlearning extortioners: unbending strategies can foster reciprocal fairness and cooperation
Authors: Chen Xingru , Fu Feng
Published: May 2023

Recent theory shows that extortioners taking advantage of the zero-determinant (ZD) strategy can unilaterally claim an unfair share of the payoffs in the Iterated Prisoner’s Dilemma. It is thus suggested that against a fixed extortioner, any adapting coplayer should be subdued with full cooperation as their best response. In contrast, recent experiments demonstrate that human players often choose not to accede to extortion out of concern for fairness, actually causing extortioners to suffer more loss than themselves. In light of this, here we reveal fair-minded strategies that are unbending to extortion such that any payoff-maximizing extortioner ultimately will concede in their own interest by offering a fair split in head-to-head matches. We find and characterize multiple general classes of such unbending strategies, including generous ZD strategies and Win-Stay, Lose-Shift (WSLS) as particular examples. When against fixed unbending players, extortioners are forced with consequentially increasing losses whenever intending to demand a more unfair share. Our analysis also pivots to the importance of payoff structure in determining the superiority of ZD strategies and in particular their extortion ability. We show that an extortionate ZD player can be even outperformed by, for example, WSLS, if the total payoff of unilateral cooperation is smaller than that of mutual defection. Unbending strategies can be used to outlearn evolutionary extortioners and catalyze the evolution of Tit-for-Tat-like strategies out of ZD players. Our work has implications for promoting fairness and resisting extortion so as to uphold a just and cooperative society.
Cognitive Uncertainty
Authors: Enke Benjamin , Graeber Thomas
Published: May 2023

This article documents the economic relevance of measuring cognitive uncertainty: people’s subjective uncertainty over their ex ante utility-maximizing decision. In a series of experiments on choice under risk, the formation of beliefs, and forecasts of economic variables, we show that cognitive uncertainty predicts various systematic biases in economic decisions. When people are cognitively uncertain—either endogenously or because the problem is designed to be complex—their decisions are heavily attenuated functions of objective probabilities, which gives rise to average behavior that is regressive to an intermediate option. This insight ties together a wide range of empirical regularities in behavioral economics that are typically viewed as distinct phenomena or even as reflecting preferences, including the probability weighting function in choice under risk; base rate insensitivity, conservatism, and sample size effects in belief updating; and predictable overoptimism and -pessimism in forecasts of economic variables. Our results offer a blueprint for how a simple measurement of cognitive uncertainty generates novel insights about what people find complex and how they respond to it.
Targeted testing of bone marrow specimens with cytoplasmic vacuolization to identify previously undiagnosed cases of VEXAS syndrome
Authors: Hines Alexander S , Koster Matthew J , Bock Allison R , Go Ronald S , Warrington Kenneth J , Olteanu Horatiu , Lasho Terra L , Patnaik Mrinal M , Reichard Kaaren K
Published: May 2023

Objective

To retrospectively identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) among male patients with bone marrow vacuolization using a clinically applicable, targeted-screening approach.

Methods

Bone marrow reports from 1 May 2014 through 18 February 2022 were reviewed for documentation of cytoplasmic vacuolization. Patients with acute leukaemia, lymphoma, metastatic solid tumour, amyloidosis or POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome were excluded, as were those without clinical records available for direct chart review. Cases were rated for suspicion of VEXAS syndrome using a 5-point scale based on the presence of laboratory findings, clinical features and treatment response. Patients with available DNA material and moderate (three patients) or high (four to five patients) suspicion were tested for somatic UBA1 variants associated with VEXAS syndrome.

Results

A total of 315 reports from 292 unique patients included documentation of vacuolization. Following exclusion criteria, 64 patients underwent direct medical chart review to assess likelihood of VEXAS syndrome, for which 21 patients met moderate to high suspicion. Available DNA was present in eight patients, seven (87.5%) of whom had a pathogenic somatic UBA1 variant consistent with VEXAS syndrome. The distribution of cytoplasmic vacuolization in the bone marrow biopsy reports among patients with VEXAS syndrome were erythroid and myeloid precursors (6/7), erythroid precursors only (1/7) and myeloid precursors only (0/7).

Conclusion

In this study, the utilization of a clinically applicable targeted-screening approach to test bone marrow specimens (with vacuolization) for the presence of previously undiagnosed VEXAS syndrome resulted in a positive detection rate of 87.5%.
Latent bone modelling for estimation of plutonium concentration in skeleton of former nuclear workers
Authors: Šefl Martin , Zhou Joey Y , Avtandilashvili Maia , Tolmachev Sergei Y
Published: May 2023

The skeleton is a major plutonium retention site in the human body. Estimation of the total plutonium activity in the skeleton is a challenging problem. For most tissue donors at the United States Transuranium and Uranium Registries, a limited number of bone samples is available. The skeleton activity is calculated using plutonium activity concentration (Cskel) and skeleton weight. In this study, latent bone modelling was used to estimate Cskel from the limited number of analysed bone samples. Data from 13 non-osteoporotic whole-body donors were used to develop latent bone model (LBM) to estimate Cskel for seven cases with four to eight analysed bone samples. LBM predictions were compared to Cskel estimated using an arithmetic mean in terms of accuracy and precision. For the studied cases, LBM offered a significant reduction of uncertainty of Cskel estimate.
Comparative re-analysis evaluation of the Fukushima accident atmospheric radioactive emissions
Authors: Pavelescu Alexandru O , Vamanu Bogdan I , Acasandrei Valentin T
Published: May 2023

In this paper, two decision support systems have been used to re-analyze the Fukushima accident emissions: the European Realtime Online Decision Support System for Nuclear Emergency Management (RODOS, version JRodos 2019)—providing a set of modules for the dispersion of nuclides following atmospheric and aquatic releases, dosimetry modules for dose estimation to individuals and communities for all exposure pathways with application of countermeasures, and modules for time estimation of the radiological situation in inhabited and agricultural areas—and CBRNE Platform, developed by IFIN-HH within a research project on anticipative and prognostic evaluation of chemical, biological, radiological, nuclear and explosive events (CBRNE), which is a tool for effect diagnosis functions, response measures and consecutive recommendation for a large variety of scenarios. We have reproduced the event on both systems, using accident time weather data and updated source terms. Current and initial results were cross-compared and evaluated.
Indoor radon concentration in state schools of four Bulgarian districts
Authors: Ivanova Kremena G , Stojanovska Zdenka , Djunakova Desislava K , Djounova Jana N , Kunovska Bistra K , Chobanova Nina A
Published: May 2023

Indoor radon concentrations were surveyed in 230 public schools in four Bulgarian districts for the period November/December 2019 to May/June 2020. The measurements were carried out in 2427 rooms on the basement, ground floor and first floor using the passive track detectors of the Radosys system. The estimated arithmetic and geometric means with standard deviations were 153 ± 154 and 114 Bq/m3 (geometric standard deviation (GSD) = 2.08), respectively. The results are higher than those referred from the National Radon Survey in dwellings. In 9.4% of the rooms, the radon concentrations were above the reference value of 300 Bq/m3. The difference between indoor radon concentrations in the districts was significant, which proves its spatial variation. The hypothesis that the applied energy efficiency measures increase indoor radon values in buildings was confirmed. The surveys demonstrated the importance of indoor radon measurements in school buildings, in order to control and reduce children’s exposure.
Machine learning-assisted antenna modelling for realistic assessment of incident power density on non-planar surfaces above 6 GHz
Authors: Kapetanović Ante , Poljak Dragan
Published: May 2023

In this paper, the analysis of exposure reference levels is performed for the case of a half-wavelength dipole antenna positioned in the immediate vicinity of non-planar body parts. The incident power density (IPD) spatially averaged over the spherical and cylindrical surface is computed at the 6–90 GHz range, and subsequently placed in the context of the current international guidelines and standards for limiting exposure to electromagnetic (EM) fields which are defined considering planar computational tissue models. As numerical errors are ubiquitous at such high frequencies, the spatial resolution of EM models needs to be increased which in turn results in increased computational complexity and memory requirements. To alleviate this issue, we hybridise machine learning and traditional scientific computing approaches through differentiable programming paradigm. Findings demonstrate a strong positive effect the curvature of non-planar models has on the spatially averaged IPD with up to 15% larger values compared to the corresponding planar model in considered exposure scenarios.
Reproduction of shielding concrete activation measurements by simulations
Authors: Hajdú Dávid , Klausz Milán , Zagyvai Péter
Published: May 2023

With the increasing number of decommissioning projects, radioactive waste estimation of biological shielding concretes is becoming more and more important. Simulation tools supporting this activity, like MCNP and Cinder are already available; however, publicly available neutron spectra in shielding concretes are limited. The aim of the study was to present and evaluate possible model arrangements for accurate neutron transport to deeper points of shielding concretes from the reactor pressure vessel. Representation of reality, neutron behavior and activity generation of seven long-lived radioisotopes (54Mn, 60Co, 65Zn, 133Ba, 134Cs, 152Eu and 154Eu) were assessed in each arrangement. After evaluating several model geometries, a conical shape neutron reflecting surface was shown to be the most suitable one to reproduce neutron fields in deeper layers of shielding concretes from a monodirectional initial neutron source.
The role of public engagement in the journey to ALARA
Authors: Bryant PA
Published: May 2023

The ‘As Low As Reasonably Achievable’ (ALARA) principle is one of the three fundamental elements of radiation protection. Noting that ionising radiation is both encountered naturally in the environment as part of everyday life, and artificially as part of a range of practices, the ALARA principle aims to provide a means of optimising radiation exposures. Historically, the stakeholders involved in the application of the ALARA process have primarily been assumed to be internal to an organisation, except for regulatory ‘buy in’. However, could there be instances when the public should be a key stakeholder? This paper explores the area of perceived risk with reference to a particular case study in which the dredging of non-hazardous sediment in the UK near a now decommissioned nuclear power station raised substantial public concern about radiological exposure. This turned what was a straightforward construction activity into a complex public engagement and reassurance task, at a significant cost disproportionate to the level of radiological risk. Learning from this case study is used to highlight the key lessons learnt and the importance of public engagement, and how perceived risk and the associated societal stress could be incorporated into the ALARA process. The paper also highlights the ongoing work and guidance produced by the Society for Radiological Protection in the UK on the development of Guidance for Practitioners to support the Communication of Radiation Risk.
Reprogramming of Acute Myeloid Leukemia Patients Cells: Harboring Cancer Mutations Requires Targeting of AML Hierarchy
Authors: Golubeva Diana , Porras Deanna P , Doyle Meaghan , Reid Jennifer C , Tanasijevic Borko , Boyd Allison L , Vojnits Kinga , Elrafie Amro , Qiao Amy , Bhatia Mickie
Published: May 2023

Screening of primary patient acute myeloid leukemia (AML) cells is challenging based on intrinsic characteristics of human AML disease and patient-specific conditions required to sustain AML cells in culture. This is further complicated by inter- and intra-patient heterogeneity, and “contaminating” normal cells devoid of molecular AML mutations. Derivation of induced pluripotent stem cells (iPSCs) from human somatic cells has provided approaches for the development of patient-specific models of disease biology and has recently included AML. Although reprogramming patient-derived cancer cells to pluripotency allows for aspects of disease modeling, the major limitation preventing applications and deeper insights using AML-iPSCs is the rarity of success and limited subtypes of AML disease that can be captured by reprogramming to date. Here, we tested and refined methods including de novo, xenografting, naïve versus prime states and prospective isolation for reprogramming AML cells using a total of 22 AML patient samples representing the wide variety of cytogenetic abnormalities. These efforts allowed us to derive genetically matched healthy control (isogenic) lines and capture clones found originally in patients with AML. Using fluorescently activated cell sorting, we revealed that AML reprogramming is linked to the differentiation state of diseased tissue, where use of myeloid marker CD33 compared to the stem cell marker, CD34, reduces reprogramming capture of AML+ clones. Our efforts provide a platform for further optimization of AML-iPSC generation, and a unique library of iPSC derived from patients with AML for detailed cellular and molecular study.
The Effect of Vitamin D3 and Valproic Acid on the Maturation of Human-Induced Pluripotent Stem Cell-Derived Enterocyte-Like Cells
Authors: Leo Sylvia , Kato Yusuke , Wu Yumeng , Yokota Mutsumi , Koike Masato , Yui Shiro , Tsuchiya Kiichiro , Shiraki Nobuaki , Kume Shoen
Published: May 2023

Cytochrome P450 3A4 (CYP3A4) is involved in first-pass metabolism in the small intestine and is heavily implicated in oral drug bioavailability and pharmacokinetics. We previously reported that vitamin D3 (VD3), a known CYP enzyme inducer, induces functional maturation of iPSC-derived enterocyte-like cells (iPSC-ent). Here, we identified a Notch activator and CYP modulator valproic acid (VPA), as a promotor for the maturation of iPSC-ent. We performed bulk RNA sequencing to investigate the changes in gene expression during the differentiation and maturation periods of these cells. VPA potentiated gene expression of key enterocyte markers ALPI, FABP2, and transporters such as SULT1B1. RNA-sequencing analysis further elucidated several function-related pathways involved in fatty acid metabolism, significantly upregulated by VPA when combined with VD3. Particularly, VPA treatment in tandem with VD3 significantly upregulated key regulators of enterohepatic circulation, such as FGF19, apical bile acid transporter SLCO1A2 and basolateral bile acid transporters SLC51A and SLC51B. To sum up, we could ascertain the genetic profile of our iPSC-ent cells to be specialized toward fatty acid absorption and metabolism instead of transporting other nutrients, such as amino acids, with the addition of VD3 and VPA in tandem. Together, these results suggest the possible application of VPA-treated iPSC-ent for modelling enterohepatic circulation.
A Decade of Hidden Phytoplasmas Unveiled Through Citizen Science
Authors: Brochu Anne-Sophie , Dionne Antoine , Fall Mamadou Lamine , Pérez-López Edel
Published: May 2023

Climate change is impacting agriculture in many ways, and a contribution from all is required to reduce the imminent losses related to it. Recently, it has been shown that citizen science could be a way to trace the impact of climate change. However, how can citizen science be applied in plant pathology? Here, using as an example a decade of phytoplasma-related diseases reported by growers, agronomists, and citizens in general, and confirmed by a government laboratory, we explored how to better value plant pathogen monitoring data. Through this collaboration, we found that in the last decade, 34 hosts have been affected by phytoplasmas; 9, 13, and 5 of these plants were, for the first time, reported phytoplasma hosts in eastern Canada, all of Canada, and worldwide, respectively. Another finding of great impact is the first report of a ‘Candidatus Phytoplasma phoenicium’-related strain in Canada, while ‘Ca. P. pruni’ and ‘Ca. P. pyri’ were reported for the first time in eastern Canada. These findings will have a great impact on the management of phytoplasmas and their insect vectors. Using these insect-vectored bacterial pathogens, we show the need for new strategies that can allow fast and accurate communication between concerned citizens and those institutions confirming their observations.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Evaluation of Wheat Cultivars and Germplasm Lines for Resistance to Pratylenchus neglectus Populations Collected in North Dakota
Authors: Singh Gurminder , KC Ashmit , Sandhu Karansher Singh , Friskop Andrew J. , Liu Zhoahui , Yan Guiping
Published: May 2023

Root-lesion nematode (RLN; Pratylenchus neglectus) is a migratory endoparasite and a major soilborne pathogen that affects wheat (Triticum spp.) production worldwide. Genetic resistance is one of the most economical and effective ways to manage P. neglectus in wheat. This study evaluated 37 local cultivars and germplasm lines in seven greenhouse experiments, including 26 hexaploid wheat, six durum wheat, two synthetic hexaploid wheat, one emmer wheat, and two triticale for P. neglectus resistance from 2016 to 2020. North Dakota field soils infested with two RLN populations (350 to 1,125 nematodes per kilogram of soil) were used for resistance screening under controlled greenhouse conditions. The final nematode population density for each cultivar and line was counted under the microscope to categorize the resistance ranking of these entries as resistant, moderately resistant, moderately susceptible, and susceptible. Out of the 37 cultivars and lines, one was classified as resistant (Brennan); 18 were moderately resistant (Divide, Carpio, Prosper, Advance, Alkabo, SY Soren, Barlow, Bolles, Select, Faller, Briggs, WB Mayville, SY Ingmar, W7984, PI 626573, Ben, Grandin, and Villax St. Jose); 11 were moderately susceptible; and seven were susceptible to P. neglectus. The resistant to moderately resistant lines identified in this study could be used in breeding programs after the resistance genes or loci are further elucidated. This research provides valuable information about P. neglectus resistance among wheat and triticale cultivars used in the Upper Midwest region of the United States.
Single‐cell transcriptome profiling reveals diverse immune cell populations and their responses to viral infection in the spleen of zebrafish
Authors: Hu Chong‐Bin , Wang Jie , Hong Yun , Li Hao , Fan Dong‐Dong , Lin Ai‐Fu , Xiang Li‐Xin , Shao Jian‐Zhong
Published: May 2023

Teleost fish are indispensable model organisms for comparative immunology research that should lead to an improved understanding of the general principles of vertebrate immune system design. Although numerous studies on fish immunology have been conducted, knowledge about the cell types that orchestrate piscine immune systems remains limited. Here, we generated a comprehensive atlas of immune cell types in zebrafish spleen on the basis of single‐cell transcriptome profiling. We identified 11 major categories from splenic leukocyte preparations, including neutrophils, natural killer cells, macrophages/myeloid cells, T cells, B cells, hematopoietic stem and progenitor cells, mast cells, remnants of endothelial cells, erythroid cells, erythroid progenitors, and a new type of serpin‐secreting cells. Notably, we derived 54 potential subsets from these 11 categories. These subsets showed differential responses to spring viremia of carp virus (SVCV) infection, implying that they have diverse roles in antiviral immunity. Additionally, we landscaped the populations with the induced expression of interferons and other virus‐responsive genes. We found that trained immunity can be effectively induced in the neutrophil and M1‐macrophage subsets by vaccinating zebrafish with inactivated SVCV. Our findings illustrated the complexity and heterogeneity of the fish immune system, which will help establish a new paradigm for the improved understanding of fish immunology.
Effective retreatment with osimertinib in CNS-relapsed epidermal growth factor receptor-mutant non-small cell lung cancer patient following resection and adjuvant osimertinib
Authors: Di Federico Alessandro , De Giglio Andrea , Sperandi Francesca , Melotti Barbara , Ardizzoni Andrea , Gelsomino Francesco
Published: May 2023

For years, adjuvant chemotherapy has been the only standard treatment for resected non-small cell lung cancer patients (NSCLC), offering a dismal survival improvement at 5 years. Following the outstanding results of the recent ADAURA trial, osimertinib has become a new standard treatment for resected epidermal growth factor receptor (EGFR)-mutant non-squamous NSCLC, regardless of the administration of chemotherapy. For patients whose disease relapses after completion of the adjuvant therapy, there is no consensus about the optimal treatment. Herein, we report the case of a 74-year-old woman diagnosed with stage IIIA non-squamous NSCLC, harboring the EGFR p.L858R mutation. After complete tumor resection, the patient received adjuvant chemotherapy with cisplatin and vinorelbine, followed by osimertinib 80 mg daily for 3 years within the ADAURA trial. Brain disease relapse was documented 18 months after treatment completion by computed tomography scans. The patient was then retreated with osimertinib obtaining a deep intracranial partial response, which is still lasting after 21 months. The retreatment with osimertinib in patients whose disease relapsed following adjuvant therapy with the third-generation EGFR inhibitor might be a valid option, especially in patients with intracranial disease relapse. Studies are warranted to confirm this finding and to define the impact of the disease-free interval in this regard.
Complete response to first-line osimertinib monotherapy in a complex epidermal growth factor receptor mutant (L833V/H835L) lung adenocarcinoma patient: a case report
Authors: Luo Zhilin , Luo Chengwen , Zhou Runquan , Xiao Yajie , Wang Tianhu
Published: May 2023

Although uncommon epidermal growth factor receptor (EGFR) mutations account for 10–15% EGFR mutant non-small cell lung cancer (NSCLC) patients, clinical evidence for uncommon EGFR mutations, such as complex mutations remain limited. In this study, we reported a NSCLC patient harboring complex EGFR L833V/H835L mutation in exon 21, who had a complete response to first-line osimertinib monotherapy. The patient admitted to our hospital for space-occupying lesions of right lower lung during an annual health checkup, and was diagnosed as stage IIIA lung adenocarcinoma. Targeted next-generation sequencing (NGS) on tumor samples showed a complex EGFR mutation: L833V/H835L in exon 21. Therefore, she was treated with osimertinib monotherapy and complete remission achieved soon. During follow-up period, no metastasis was found and serum carcinoembryonic antigen returned to normal. In addition, NGS monitoring of mutations in circulating tumor DNA maintained negative. The patient remain benefitted for osimertinib monotherapy over 22 months with no disease progression. Our case firstly provided clinical evidences of first-line osimertinib therapy in lung cancer patients with rare L833V/H835L EGFR mutation.
Recognizing and Reducing Delirium in the Intensive Care Unit
Authors: Dechant Thomas , Smith Lauren , Chavez Jose
Published: May 2023

This article discusses a quality improvement study conducted on intensive care unit (ICU) staff nurses that assessed their ability to utilize the CAM-ICU tool for delirium detection properly. Staff members' expertise in identifying and managing delirious patients directly correlates with reducing the long-term sequelae associated with ICU delirium. The cohort of ICU nurses participating in this research study took a questionnaire on 4 separate occasions. The survey ascertained quantitative and qualitative data, reflecting personal knowledge about the CAM-ICU tool and delirium. After each round of assessment, group and one-on-one educational sessions were provided by the researchers. The study culminated with providing each staff member a delirium reference card (badge buddy) containing relevant and easily accessible clinical information that supported the ICU staff nurses in correctly implementing the CAM-ICU tool.
Evaluating Metformin Strategies for Cancer Prevention: A Target Trial Emulation Using Electronic Health Records
Authors: Dickerman Barbra A. , García-Albéniz Xabier , Logan Roger W. , Denaxas Spiros , Hernán Miguel A.
Published: May 2023

Background:

Metformin users appear to have a substantially lower risk of cancer than nonusers in many observational studies. These inverse associations may be explained by common flaws in observational analyses that can be avoided by explicitly emulating a target trial.

Methods:

We emulated target trials of metformin therapy and cancer risk using population-based linked electronic health records from the UK (2009–2016). We included individuals with diabetes, no history of cancer, no recent prescription for metformin or other glucose-lowering medication, and hemoglobin A1c (HbA1c) <64 mmol/mol (<8.0%). Outcomes included total cancer and 4 site-specific cancers (breast, colorectal, lung, and prostate). We estimated risks using pooled logistic regression with adjustment for risk factors via inverse-probability weighting. We emulated a second target trial among individuals regardless of diabetes status. We compared our estimates with those obtained using previously applied analytic approaches.

Results:

Among individuals with diabetes, the estimated 6-year risk differences (metformin – no metformin) were −0.2% (95% CI = −1.6%, 1.3%) in the intention-to-treat analysis and 0.0% (95% CI = −2.1%, 2.3%) in the per-protocol analysis. The corresponding estimates for all site-specific cancers were close to zero. Among individuals regardless of diabetes status, these estimates were also close to zero and more precise. By contrast, previous analytic approaches yielded estimates that appeared strongly protective.

Conclusions:

Our findings are consistent with the hypothesis that metformin therapy does not meaningfully influence cancer incidence. The findings highlight the importance of explicitly emulating a target trial to reduce bias in the effect estimates derived from observational analyses.
Applied Usage and Tips of High Stretch Fixation NPWTi-d for Sternal Osteomyelitis
Authors: Cho Hoyu , Eura Shigeyoshi , Watanabe Kumi , Kamii Yukie , Ogawa Rei
Published: May 2023

Sternal osteomyelitis is a rare but devastating complication of median sternotomy. To achieve good outcomes, it should be diagnosed early and treated appropriately. Standard treatment involves antibiotics, debridement, and reconstruction with flaps. To prevent flap complications and recurrence, the wound bed must be prepared carefully. One approach, a recent development, is negative pressure wound therapy with instillation and dwell time (NPWTi-d), where suction cycles are interspersed with wound instillation with solutions. NPWTi-d is currently cautioned against for large trunk wounds and cavities because it might alter core body temperature. Here, we report a new NPWTi-d dressing technique that is associated with successful reconstruction in two severe sternal osteomyelitis cases with wound sizes of 29 × 10 and 28 × 8 cm. This “delay-dressing technique” involves manually pulling the wound edges together; inserting a thin strip of dressing foam; applying dressing film strips from one side of the chest wall to the other, thus placing strong stretching tension on the normal skin around the wound; and then applying NPWTi-d. In our cases, we used the V.A.C. Ulta system for 20 and 17 days. The successful reconstruction in both cases may reflect good wound bed preparation and flap preconditioning due to the mechanical stress imposed by NPWTi-d. Thus, this dressing technique with the V.A.C. Ulta system may be an effective treatment option for sternal osteomyelitis cases.
Insemination “Fraud”: Potentially Criminal Actions in Reproductive Medicine
Authors: King Louise P. , Kettering Caroline , Sanfilippo Joseph S.
Published: May 2023

Case law and statutory provisions ensure marital rules of paternity apply when artificial insemination is associated with the pregnancy. Virtually all jurisdictions in the United States provide for gamete donors to remain anonymous. Much of this has been challenged with access to donor information via 23 and me. A breach of trust and a number of lawsuits involving physician provider(s) have resulted. We provide case law examples related to artificial insemination and the identification of the sperm donor. Proposed future legislation to protect patients and offspring from harm in relation to the process of donor sperm inseminations is provided.
Retinal vasculitis severity assessment: intra- and inter-observer reliability of a new scheme for grading wide-field fluorescein angiograms in retinal vasculitis
Authors: Dhirachaikulpanich Dhanach , Madhusudhan Savita , Parry David , Babiker Salma , Zheng Yalin , Beare Nicholas AV
Published: May 2023

Purpose:

Wide-field fluorescein angiography (WFFA) is commonly used to assess retinal vasculitis (RV), which manifests as vascular leakage and occlusion. Currently, there is no standard grading scheme for RV severity. We propose a novel RV grading scheme and assess its reliability and reproducibility.

Methods:

A grading scheme was developed to assess both leakage and occlusion in RV. WFFA images from 50 RV patients were graded by four graders, and one grader graded them twice. Intra-class correlation coefficient (ICC) was used to determine intra-interobserver reliability. Generalized linear models (GLM) were calculated to associate the scoring with visual acuity.

Results:

Repeated grading by the same grader showed good intraobserver reliability for both leakage (ICC = 0.85, 95%CI 0.78-0.89) and occlusion (ICC = 0.82, 95%CI 0.75-0.88) scores. Interobserver reliability among 4 independent graders showed good agreement for both leakage (ICC = 0.66, 95%CI 0.49-0.77) and occlusion (ICC = 0.75, 95%CI 0.68-0.81) scores. Increasing leakage score was significantly associated with worse concurrent visual acuity (GLM, β=0.090, p<0.01) and at 1-year follow-up (GLM, β=0.063, p<0.01).

Conclusion:

Our proposed grading scheme for RV has good to excellent intra and interobserver reliability across a range of graders. The leakage score related to present and future visual acuity.
Clinical Utility of Ileal Motility in Children With Defecation Disorders and Children With Chronic Intestinal Pseudo-Obstruction
Authors: Colliard Kitzia , Nurko Samuel , Flores Alejandro , Rodriguez Leonel
Published: May 2023

Background:

Little is known about ileal motility patterns and their utility in children. Here, we present our experience with children undergoing ileal manometry (IM).

Methods:

A retrospective review of children with ileostomy comparing IM between 2 groups: A [chronic intestinal pseudo-obstruction (CIPO)] and B (feasibility of ileostomy closure in children with defecation disorders). We also compared the IM findings with those from antroduodenal manometry (ADM), and evaluated the joint effect of age, sex, and study indication group on IM results.

Results:

A total of 27 children (median age 5.8 years old, range 0.5–16.74 years, 16 were female) were included (12 in group A and 15 in group B). There was no association between IM interpretation and sex; however younger age was associated with abnormal IM (P = 0.021). We found a significantly higher proportion of patients with presence of phase III of the migrating motor complex (MMC) during fasting and normal postprandial response in group B than in group A (P < 0.001). Logistic regression analysis revealed that only Group B was associated with normal IM (P < 0.001). We found a moderate agreement for the presence of phase III MMC and postprandial response between IM and ADM (kappa = 0.698, P = 0.008 and kappa = 0.683, P = 0.009, respectively).

Conclusion:

IM is abnormal in patients with CIPO and normal in patients with defecation disorders, suggesting that IM may be not needed for ostomy closure in those with defecation disorders. IM has a moderate agreement with ADM and could be used as a surrogate for small bowel motility.
NOD2 Polymorphisms May Direct a Crohn Disease Phenotype in Patients With Very Early-Onset Inflammatory Bowel Disease
Authors: Watson Ashleigh , Forbes Satter Lisa , Reiland Sauceda Ashley , Kellermayer Richard , Karam Lina B.
Published: May 2023

NOD2/CARD15 was the first susceptibility gene recognized for adult-onset Crohn’s (or Crohn) disease (CD). Recessive inheritance of NOD2 polymorphisms has been implicated as a mechanistic driver of pediatric-onset CD. In patients with very early-onset inflammatory bowel disease (VEO-IBD), however, the clinical relevance of NOD2 polymorphisms has not been fully established. Ten VEO-IBD patients with NOD2 polymorphisms (NOD2+) were compared to 16 VEO-IBD patients without genetic variants in NOD2 or any other VEO-IBD susceptibility genes (NOD2−). The majority of NOD2+ patients exhibited a CD-like phenotype (90%), linear growth impairment (90%), and arthropathy (60%), all of which were significantly more common than in the NOD2− group (P = 0.037, P = 0.004, P = 0.026, respectively). We propose that the presence of NOD2 polymorphisms in patients with VEO-IBD might confer a CD-like phenotype, linear growth impairment, and arthropathy. These findings should be validated in larger cohorts and may guide precision medicine for patients with VEO-IBD in the future.
Work of Eels Setting a Dilemma for Forensic Pathologist
Authors: Goel Rohit , S Agnes Daney Angela , Amarnath Arthy , Subramanyam Sunil
Published: May 2023

After the death of an individual, the body may be affected by various natural processes, including the effects of environmental factors and predation by micro-organisms and macro-organisms, which can produce a variety of artifacts. These artifacts can then pose a challenge to forensic personnel, such as whether such activity was antemortem or postmortem in nature and, if antemortem, whether such animal activities contributed to the death of an individual. This case report is a rare example of an interesting postmortem artifact of the presence of moray eels within a corpse. To the best of our knowledge, this is the first reported case of such a finding.
Trigeminal Nerve Isolation Application in Microvascular Decompression for Treating Trigeminal Neuralgia: A Retrospective Study
Authors: Song Wenxiong , Ding Feiyu , Hu Xinhua , Yang Kun , Liu Yong , Chen Yongyan , Huang Qingjiu , Zou Yuanjie , Geng Liangyuan
Published: May 2023

This study aimed to compare the outcomes of trigeminal nerve isolation (TNI) with conventional microvascular decompression (CMVD) in cases of trigeminal neuralgia (TN). We retrospectively reviewed 143 TN cases who underwent microvascular decompression from January 2017 to January 2020. The surgical management of TNI or CMVD in all patients was randomized. The cases were divided into two groups, one group underwent a TNI and the other one received CMVD. The general data, postoperative outcomes, and complications were reviewed retrospectively. Cases with a narrow cistern of cerebellopontine, short trigeminal nerve root, and arachnoid adhesion were defined as difficult cases. All of the cases were followed up for at least 1 year. Surgical outcomes were assessed and compared between the two groups. In results, we found no significant differences in the general data, duration of hospitalization and blood loss between the two procedures. However, of the 143 cases, 12 cases (17.1%) recurred after surgery in the CMVD group, and four cases (5.5%) recurred after TNI operation. The rates of pain relief were 69 (94.5%) in the CMVD group, and 58 (82.9%) for TNI (P=0.027). In the TNI group, there was only one difficult case among four no pain-relief cases, while in the CMVD group, 10 difficult cases were found among the 12 no pain-relief cases (P=0.008). In conclusion, the TNI technique is more effective than the CMVD procedure and could also be performed on patients with classical TN. Future double-blind and randomized controlled trials are necessary to confirm this result.
Large Lipoma with Focal Cartilage Metaplasia of the Under-tongue Region
Authors: Russo Federico , Berardi Luigi , Karligkiotis Apostolos
Published: May 2023

Lipomas are benign connective tissue tumors. They are common lesions in the human body, but they rarely appear in the oral cavity. We present a case of a 31-year-old female with a 2 months history of painful swelling of the under-tongue region, without dysphagia and dyspnea. The neoformation was surgically removed with a trans-oral approach. The pathological diagnosis was lipoma with focal cartilage metaplasia. Good healing of surgical site was observed, without complications and persistence of the lesion.
Patient Tailored Surgery in Saethre-Chotzen Syndrome: Analysis of Reoperation for Intracranial Hypertension
Authors: Kurzbuch Arthur R. , Cooper Ben , Duncan Christian , Ellenbogen Jonathan , Richardson David , Sinha Ajay , Weber Astrid , Sithambaram Sivagamy , Hennedige Anusha , Parks Chris
Published: May 2023

Saethre-Chotzen syndrome (SCS) is a syndromic craniosynostosis with pathogenic variants in the TWIST1 gene showing a broad phenotypic spectrum. Controversies exist in the literature regarding surgical management with single one-stage versus patient-tailored surgery and the related reoperation rate for intracranial hypertension of up to 42%. At our center, SCS patients are offered patient-tailored surgery with single-stage fronto-orbital advancement and remodeling or fronto-orbital advancement and remodeling and posterior distraction in an individually determined order. The authors’ database identified 35 confirmed SCS patients between 1999 and 2022. Involved sutures in craniosynostosis were left unicoronal (22.9%), bicoronal (22.9%), sagittal (8.6%), bicoronal and sagittal (5.7%), right unicoronal (2.9%), bicoronal and metopic (2.9%), bicoronal, sagittal and metopic (2.9%), and bilateral lambdoid (2.9%). There was pansynostosis in 8.6% and no craniosynostosis in 14.3% of the patients. Twenty-six patients, 10 females, and 16 males were operated on. Mean age at the first surgery was 1.70 years, and 3.86 years at the second surgery. Eleven of 26 patients had invasive intracranial pressure monitoring. Three patients presented with papilledema before the first surgery and 4 afterward. Four of the 26 operated patients were operated initially elsewhere. The other 22 patients were initially referred to our unit and underwent patient-tailored surgery. Nine of these patients (41%) had a second surgery, and 3 (14%) of them were because of raised intracranial pressure. Seven (27%) of all operated patients had a complication. Median follow-up was 13.98 years (range, 1.85–18.08). Patient-tailored surgery in a specialized center and long-term follow-up allow for a low reoperation rate for intracranial hypertension.
The Vibrio vulnificus stressosome is dispensable in nutrient-rich media
Authors: Cutugno Laura , Mc Cafferty Jennifer , Pané-Farré Jan , O'Byrne Conor , Boyd Aoife
Published: May 2023

The stressosome is a protein complex that senses environmental stresses and mediates the stress response in several Gram-positive bacteria, through the activation of the alternative sigma factor SigB. The stressosome locus is found in 44% of Gram-negative Vibrio vulnificus isolates. However, V. vulnificus does not possess SigB. Nonetheless, in nutrient-limited media, the stressosome modulates gene transcription and bacterial behaviour.
In this work, the expression of the stressosome genes was proven during stationary phase in nutrient-rich media and the co-transcription as one operonic unit of the stressosome locus and its putative downstream regulatory locus was demonstrated. The construction of a stressosome mutant lacking the genes encoding the four proteins constituting the stressosome complex (VvRsbR, VvRsbS, VvRsbT, VvRsbX) allowed us to examine the role of this complex in vivo. Extensive phenotypic characterisation of the ΔRSTX mutant in nutrient-rich media showed that the stressosome does not contribute to growth of V. vulnificus. Moreover, the stressosome did not modulate the tolerance or survival response of V. vulnificus to the range of stresses tested, which included ethanol, hyperosmolarity, hypoxic, high temperature, acidity and oxidative stress. Furthermore, the stressosome was dispensable for motility and exoenzyme production of V. vulnificus in nutrient-rich media-.
Therefore, in conclusion, although stressosome gene transcription occurs in nutrient-rich media, the stressosome neither has an essential role in stress responses of V. vulnificus, nor does it seem to modulate these activities in these conditions. We hypothesise that the stressosome is expressed in nutrient-rich conditions as a sensor complex, but that activation of the complex does not occur in this environment.
Real-world performance and safety of Halova®ovules in reducing the vaginal symptoms associated with vulvovaginal atrophy and postmenopausal sexual dysfunction
Authors: Iliescu Dominic-Gabriel , Petrita Ramona , Teodorescu Cristina , Olaru Raluca Alexandra , Alexa Andreea Anda , Petre Izabella
Published: May 2023

Decreasing sex hormones levels during the postmenopausal period results in tissue atrophy and physiological changes, such as thinning of the vaginal epithelium, prolapse, and decreased pelvic floor strength and control. Sexual dysfunction associated with vaginal dryness has frequently been reported in postmenopausal women. The present study was designed as an observational, multicenter, real-world clinical investigation to evaluate the performance and safety of the medical device Halova®ovules in reducing vaginal symptoms associated with vulvovaginal atrophy and sexual dysfunction. A total of 249 female participants were treated with Halova®ovules, both in monotherapy and in combination with concomitant medication. The primary objective of this study was to evaluate the tolerability of Halova®ovules in the management of symptoms associated with perimenopause or genitourinary syndrome of menopause. The evolution of clinical manifestations such as vaginal dryness, dysuria, dyspareunia, and endometrial thickness in patients with the aforementioned conditions was defined as a secondary objective. Halova®ovules were rated with “excellent” clinical performance by 92.74% of the study participants as a standalone treatment and 95.71% of the study participants when used in association. Sexual dysfunction-related parameters, such as vaginal dryness and dyspareunia, were reduced by similar percentages in each arm. No adverse reactions related to treatment with Halova®have been reported. Halova®may be a therapeutic alternative for patients with controversial local estrogenic treatment. The study and its details are registered withNCT05654610.