bluuebunny/crossref_metadata_2025 huggingface dataset:
P09 Attitudes, barriers and difficulties to discharge – a qualitative approach
Authors: Lukaszewicz A , Linganathan S
Published: May 2023

Introduction

It is well accepted that prompt and effective discharges are crucial in order to sustain patient continuity of care, patient flow and create bed space for patients. Systematic difficulties and the health professional staffing crisis may create further barriers to satisfying the above statement. Thus, the authors have investigated the titled characteristics with a view to instigating beneficial changes.

Methods

A curated questionnaire was designed and emailed to all health care professionals who worked within the general surgical department at the authors’ trust who completed discharge summaries. A total of 26 respondents completed the survey.

Results

The main obstacle in completing discharges was lack of patient knowledge (40% of respondents) followed by time pressure (28% of respondents). In addition, each discharge usually took 11 minutes or more. Discharge priority is deemed to be of variable importance, with 52% ranking it as moderate priority and 24% deeming it to be high priority. Multiple symbiotic factors were thought to be important in improving the discharge process. However, the single key factor was dedicated protected time to complete discharge paperwork (17.39% of respondents). 60% of respondents ideally favoured a typed discharge summary with 28% preferring dictation despite a lack of knowledge and understanding of the available resources.

Conclusion

This work has offered a valuable insight into the attitudes, barriers and difficulties surrounding discharges with scope to instigate improvements, such as the use of dictation software, protected time and subsequent possible policy changes.
P11 Satisfaction rates with telephone follow-up clinic appointments
Authors: Murugan V , Wong T , Fouad M , Sanyal S
Published: May 2023

Introduction

Since the onset of the COVID-19 pandemic, telephone follow-up (TFU) clinics have been an integral part of delivering healthcare. Advantages of telephone clinics include reducing costs and increasing efficiency. This quality improvement project (QIP) aims to evaluate patient satisfaction rates in a hot biliary telephone clinic.

Methods

The Likert-scale is a 13-item questionnaire tool ranging from 1-5 (1=strongly disagree, 5=strongly agree) and was used to assess patient satisfaction with TFUs. Satisfactory cut-off point (score of 4) was analysed across all responses. Retrospective questionnaires were completed for 100 consented patients. Outcomes included overall satisfaction rate across gender and age groups.

Results

Overall, 75% of patients were satisfied with TFUs. No statistical difference was found between male and female rates of satisfaction (67.6% and 79.4% respectively, p-value=0.19). Likewise, satisfaction rates did not differ by age (< 50 years: 72.2%, 50-59years: 88.9%, 60-69years: 71.4% and >70years: 72%, p-value: 0.52).

Conclusion

Most patients were satisfied with TFUs. However, despite initial positive findings, there is still room to improve satisfaction. Prior to a re-evaluation, interventions such as offering patients the option of a telephone consult or a face-to-face appointment will be considered.
P13 Entrepreneurship in plastic surgery – a single departmental experience
Authors: Sequeira Campos M , Brady C , Ponniah A
Published: May 2023

Introduction

The specialty of Plastic and reconstructive surgery has long been at the forefront of innovation. However, perceptions of individuals focusing on entrepreneurship, particularly at a junior level, remain unclear. Anecdotally, trainees can be discouraged from participating in entrepreneurial efforts for fear of seniors’ disapproval.

Methods

A questionnaire was circulated amongst doctors at the Royal Free Plastic Surgery department aiming to establish knowledge and perceptions of entrepreneurship. It included 10 questions to be answered anonymously.

Results

18 individuals responded, including Foundation doctors (n=2), Junior clinical fellows (n=2), Core surgical trainees (n=3), Specialty registrars (n=5), Senior clinical fellows (n=2) and Consultants (n=4). All respondents (n=18) understood the meaning of the term “entrepreneurship” and 44.4% (n=8) had prior entrepreneurship experience. Perceptions of the connotations of the word “entrepreneurship” in surgery varied. 33% (n=6) reported “strongly negative” and 33% (n=6) “strongly positive” connotations. Notably, of those reporting “strongly negative” connotations, 80% (n=4) were junior trainees at Core surgical training or below, and 20% (n=1) were specialty registrars. Amongst the 4 consultants, mean perception on a 5-point scale was 3.75, indicating an overall “positive” connotation. Furthermore, 83.3% (n=15) of respondents felt their surgical career had not provided them with opportunities to develop entrepreneurship skills and 94.4% (n=17) would like further opportunities to develop entrepreneurship skills.

Conclusion

Perceptions on involvement in entrepreneurship in surgery are predominantly positive. Those associating entrepreneurial efforts with negative connotations seem to be predominantly junior. This result will hopefully encourage Plastic surgeons at all levels to become involved in entrepreneurial efforts.
P15 Prosthetic venous valves: short history and advancements from 2012 to 2020
Authors: Zervides C , Mahdi H , Staub R , Jouni H
Published: May 2023

Introduction

Venous diseases affect a majority of the population. It has both medical and cosmetic impacts on patients well-being. Patients have severe complications due to deep venous disease with few available therapies. A faulty venous valve is the origin of venous diseases, yet the treatment of such venous valves is invasive with a high recurrence rate. A prosthetic venous valve replacement is imminent and possibly provides better outcomes.

Methods

Articles addressing emerging implantable venous valve designs were examined. A systematic search resulted in thirty-five papers fitting the inclusion criteria. The focus was on the jugular vein and lower limbs veins and publication after 2012.

Results

Although no commercial model is in the market, many designs and models were studied especially in recent years. It was found that the composition of the valve determines its shape and the presence of inter/intra valve variability improved the approach toward a successful design. Three major models have been tested on animals awaiting further trials. Hence, a criterion for a successful prosthetic valve was formulated to avoid major complications and ensure the stability and durability of the valve.

Conclusion

The aim of the review is to shed light on the possible evolution in deep venous disease management especially since no ideal valve is available. If implemented, it can act as a treatment for early venous disease or to improve the quality of life if no alternative is available.
P17 Platelet-rich plasma as a treatment for vulval lichen sclerosus: a systematic review of safety and efficacy
Authors: Jasionowska S , Goble M , Langridge B , Iakovou D , Kamel F , McKenzie M , Almadori A , Butler P
Published: May 2023

Introduction

Vulval lichen sclerosus (VLS) is an inflammatory skin disease characterised by pain, itching, burning, apareunia, loss of vulval architecture and scarring. VLS has a significant impact on patients’ quality of life and certain patients find no symptomatic relief in the gold standard treatment of topical corticosteroids. Platelet-rich plasma (PRP) is derived from autologous plasma and injected into disease areas, it may provide superior outcomes for patients than current treatment options. This study systematically reviewed the safety and efficacy of platelet-rich plasma as a treatment for VLS.

Methods

This review followed PRISMA guidelines using a registered protocol (PROSPERO:CRD42022379894). Multiple databases were searched, along with grey literature on Clinicaltrials.gov, European Union Clinical Trials, and International Standard Randomised Controlled Trial registries. All studies evaluating the safety and/or efficacy of PRP for VLS were included.

Results

A total of 213 patients were assessed across nine studies. There was significant heterogeneity between studies, in the study design, PRP preparation method and injection volume of plasma used, and outcome measures. Forty-one percent (n=88) of patients reported resolution of symptoms on Quality-of-Life outcome measures or symptom assessment scales, 6% (n=12) patients had histological improvement of inflammation. PRP demonstrated symptom resolution and improvement, however the evidence is insufficient to conclude on its effectiveness or safety, and heterogenous outcome measures preclude pooled data analysis.

Conclusion

PRP may provide superior results than corticosteroids in certain patients with VLS, however further research is needed to ascertain the safety and efficacy profile of this treatment.
Validation of a microwave energy meter to non-lethally estimate energetic reserves in adult sturgeon
Authors: Daigle Nicole J , Djokic Matea A , Kappenman Kevin M , Gaylord T Gibson , Quinn Sierra , Verhille Christine E
Published: May 2023

Whole-body (WB) energetic reserves influence fish survival, growth, and reproduction but are typically quantified using lethal methods (i.e. proximate analyses) or interpreted through body condition indices. Energetic reserves can impact population dynamics through influences on growth rates, age-at-first-reproductive-maturity, and spawning periodicity at the individual-fish level, especially in long-lived sturgeon species. Therefore, a non-lethal tool to track the energetic reserves of endangered sturgeon populations could inform adaptive management and further our understanding of the sturgeon’s biology. The Distell Fatmeter is a microwave energy meter that has been validated to non-lethally estimate energetic reserves in some fish species, but never successfully for sturgeon. Here, stepwise linear regressions were applied to test commonly monitored body metrics and Fatmeter measurements at nine different anatomical sites on captive adult pallid sturgeon (Scaphirhynchus albus; total length of 790–1015 mm; WB lipid of 13.9–33.3%) compared with WB lipid and energy content determined by proximate analyses. Fatmeter measurements alone explained approximately 70% of the variation in WB energetic reserves, which outperformed models considering body metrics alone by a margin of approximately 20%. The top-ranked models based on AICc score (second-order Akaike Information Criterion) included a combination of body metrics and Fatmeter measurements and accounted for up to 76% of the variation in WB lipid and energy. We recommend the incorporation of Fatmeter measurements at a single site located dorsally to the lateral scutes at the posterior end of the fish above the pelvic fins (U-P) into conservation monitoring programs for adult pallid sturgeon (total length [TL] ≥ 790 mm; fork length [FL] ≥ 715 mm) and the cautious application of Fatmeter measurements for sturgeon between 435 and 790 mm TL (375–715 mm FL). Measurements at this U-P site combined with body mass explained approximately 75% of the variation in WB lipid and energy.
Strategies to mitigate emergency department crowding and its impact on cardiovascular patients
Authors: Baugh Christopher W , Freund Yonathan , Steg Philippe Gabriel , Body Richard , Maron David J , Yiadom Maame Yaa A B
Published: May 2023

Emergency department (ED) crowding is a worsening global problem caused by hospital capacity and other health system challenges. While patients across a broad spectrum of illnesses may be affected by crowding in the ED, patients with cardiovascular emergencies—such as acute coronary syndrome, malignant arrhythmias, pulmonary embolism, acute aortic syndrome, and cardiac tamponade—are particularly vulnerable. Because of crowding, patients with dangerous and time-sensitive conditions may either avoid the ED due to anticipation of extended waits, leave before their treatment is completed, or experience delays in receiving care. In this educational paper, we present the underlying causes of crowding and its impact on common cardiovascular emergencies using the input–throughput–output process framework for patient flow. In addition, we review current solutions and potential innovations to mitigate the negative effect of ED crowding on patient outcomes.
The underutilization of preventive cardiovascular measures in patients with cancer: an analysis of the Behavioural Risk Factor Surveillance System, 2011–22
Authors: Sayed Ahmed , Munir Malak , Addison Daniel , Abushouk Abdelrahman I , Dent Susan F , Neilan Tomas G , Blaes Anne , Fradley Michael G , Nohria Anju , Moustafa Khaled , Virani Salim S
Published: May 2023

Aims

This study aimed to characterize the influence of a cancer diagnosis on the use of preventive cardiovascular measures in patients with and without cardiovascular disease (CVD).

Methods and results

Data from the Behavioural Risk Factor Surveillance System Survey (spanning 2011–22) were used. Multivariable logistic regression models adjusted for potential confounders were applied to calculate average marginal effects (AME), the average difference in the probability of using a given therapy between patients with and without cancer. Outcomes of interest included the use of pharmacological therapies, physical activity, smoking cessation, and post-CVD rehabilitation. Among 5 012 721 respondents, 579 114 reported a history of CVD (coronary disease or stroke), and 842 221 reported a diagnosis of cancer. The association between cancer and the use of pharmacological therapies varied between those with vs. without CVD (P-value for interaction: <0.001). Among patients with CVD, a cancer diagnosis was associated with a lower use of blood pressure-lowering medications {AME: −1.46% [95% confidence interval (CI): −2.19% to −0.73%]}, lipid-lowering medications [AME: −2.34% (95% CI: −4.03% to −0.66%)], and aspirin [AME: −6.05% (95% CI: −8.88% to −3.23%)]. Among patients without CVD, there were no statistically significant differences between patients with and without cancer regarding pharmacological therapies. Additionally, cancer was associated with a significantly lower likelihood of engaging in physical activity in the overall cohort and in using post-CVD rehabilitation regimens, particularly post-stroke rehabilitation.

Conclusion

Preventive pharmacological agents are underutilized in those with cancer and concomitant CVD, and physical activity is underutilized in patients with cancer in those with or without CVD.

Lay Summary

•This paper compared the use of preventive cardiovascular measures, both pharmaceutical and non-pharmaceutical, in patients with and without cancer.

•In patients with cardiovascular disease and cancer, there is a lower use of preventive cardiovascular medications compared with those with cardiovascular disease but without cancer. This includes a lower utilization of blood pressure-lowering medications, cholesterol-lowering medications, and aspirin.

•Patients with cancer reported lower levels of exercise but higher levels of smoking cessation compared with those without cancer
For a Universal Standard for Conflicts Disclosures
Authors: Mourre Alexis
Published: May 2023

Amongst the many reforms of international arbitration that are currently discussed, the adoption of a universal standard for conflicts disclosures is particularly necessary. Currently, the subjective standard “in the eyes of the parties” that is adopted by the IBA Guidelines and the ICC Rules coexist with the objective standard “from the perspective of a fair-minded and informed observer”, as defined by the English Supreme Court in Halliburton. The author submits that the IBA-ICC standard is preferable for it fosters more complete disclosures and encourages transparency. However, the subjective standard does not eliminate the moral hazard of non-disclosures and the author recommends that it be combined with a purely objective requirement to disclose based on a pre-established list of circumstances.
WTO Rules for Trade with Disputed Territories
Authors: Kanevskaia Olia
Published: May 2023

The legality of trade with territories over which sovereignty is disputed has recently come to the forefront of policy and academic discussions due to emerging case law and escalating territorial conflicts. While considerations shaping the debate on economic activities with disputed territories are typically informed by concerns of international law, little is known about international trade and customs rules applicable to these regimes. This article aims to fill this literature gap by inquiring into the rules that apply to trade with disputed territories under the relevant World Trade Organization (WTO) Agreements, in particular the General Agreement on Tariffs and Trade, the Agreement on Rules of Origin, and the Agreement on Technical Barriers to Trade. In a broader sense, it contributes to the understanding of interactions between the WTO and other self-containing regimes of international law, illustrating the challenges that arise from their different approaches to territories.
Taking Ideas Seriously in Political Science: The Diffusion of Presidentialism in Latin America after Independence
Authors: Parsons Craig , Garcé Adolfo , Béland Daniel
Published: May 2023

Today it is rare to find a political scientist who rejects that “ideas matter”—at least in the abstract. But if ideationally inclined theorists have gained seats at the disciplinary table, their approaches still occupy disadvantaged positions. Ideational theories typically must confront nonideational alternatives to achieve salient publication, but nonideational theorists routinely design and publish research without considering ideational alternatives. This is even true on topics where all scholars seem to agree a priori on the importance of ideas. Erratic attention to ideas appears to be justified by widespread views that even if ideas plausibly “matter,” they are too intractable to address in concrete research: too difficult to measure empirically, to relate in explanatory ways to action, or to connect to goals of theoretical generalization. This article first highlights major problems with these views in the abstract, and then illustrates them in the example of early Latin American constitutional design. On this terrain, there are good reasons to think that an ideational account connects in more concrete ways to available evidence than leading nonideational hypotheses about constitutional choice. Political science should move toward better balanced debates between plausible explanations, upgrading the rigor of the discipline overall.
Under-The-Nose Versus Over-The-Nose Face Mask to Prevent Facial Pressure Sores During Face Mask-Delivered Noninvasive Ventilation for Acute Hypercapnic Respiratory Failure: A Randomized Controlled Trial
Authors: Lemyze Malcolm , Mallat Jihad , Vangrunderbeek Nicolas , Granier Maxime
Published: May 2023

OBJECTIVES:

To determine whether an under-the-nose face mask (FM) as the first-line interface strategy reduces the incidence of facial pressure sores with the same clinical improvement as the one obtained by standard over-the-nose face mask-noninvasive ventilation (FM-NIV) in patients with acute hypercapnic respiratory failure (AHRF).

DESIGN:

A multicenter, prospective randomized controlled study.

SETTING:

Two ICUs from two French tertiary hospitals.

PATIENTS:

A total of 108 patients needed NIV for AHRF.

INTERVENTIONS:

participants were randomized (1/1) to receive either the under-the-nose FM (intervention group) or the over-the-nose FM (control group). The primary endpoint was the reduction of facial pressure sores. Secondary endpoints included patients outcome, NIV failure (intubation or death), arterial blood gas improvement, and interface failure (the need to switch to a total face mask).

MEASUREMENTS AND MAIN RESULTS:

Despite less protective dressings in the intervention group (n = 4, 5% vs n = 27, 51%; p < 0.001), pressure sores developed less frequently than in the control group (n = 3, 5% vs n = 39, 74%; p < 0.001). Similar mortality, NIV failure, and arterial blood gas improvement occurred in the two groups. However, under-the-nose FM resulted in a higher interface failure rate than conventional FM (n = 18, 33% vs n = 5, 9%; p = 0.004), mainly because of excessive unintentional air leaks (n = 15, 83% vs n = 0, 0%; p < 0.001).

CONCLUSIONS:

In patients with AHRF, under-the-nose FM significantly reduced the incidence of facial pressure sores compared to the most commonly used first-line interface, the standard FM. However, with this new mask, excessive unintentional air leaks more often compelled the attending clinician to switch to another interface to pursue NIV.
Clinicopathological demographics of malignant melanomas of the vulva and vagina in Japan
Authors: Ogata Dai , Nishio Shin , Hatta Naohito , Kaji Tatsuya , Fujii Kazuyasu , Mikami Mikio , Kiyohara Yoshio , Enomoto Takayuki
Published: May 2023

Malignant vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of rare malignant melanomas with critical biological properties that differ from other cancers. In Japan, adequate surveys have yet to be conducted. This study aimed to elucidate the clinicopathological demographics and outcomes of VuM and VaM in Japan. This retrospective observational study included women with invasive VuM or VaM identified from older medical records in Japan. We collected clinical data and used the Kaplan–Meier method to analyze progression-free survival (PFS) and overall survival (OS). Univariate and multivariate regression models were used to identify factors significantly related to survival. We identified 217 patients, 109 (50.2%) with VuM and 108 (49.8%) with VaM. The median PFS was 16.8 months in patients with VuM [95% confidence interval (CI), 23.1–87.7] and 15.6 months in those with VaM (95% CI, 8.4–12.6). The median OS was 43.9 months (95% CI, 60–138) and 31.1 months (95% CI, 24.8–45.3) in patients with VuM and VaM, respectively. Multivariate analysis showed that a disease stage higher than stage III, based on the American Joint Committee on Cancer (AJCC) guidelines, was associated with poorer PFS [hazard ratio (HR), 2.063; 95% CI, 0.995–4.278] and an unknown surgical margin was the only independent factor influencing OS (HR, 2.188; 95% CI, 1.203–3.977). The overall outcomes of invasive VuM and VaM in Japan remain poor. AJCC staging and surgical margins were significant predictors of survival.
18F-FDG PET/CT in Extensive Follicular Dendritic Cell Sarcoma With Response Assessment to Chemotherapy
Authors: Prakash Kavali David Jaya , Sharma Siddharth , Nazar Aftab Hasan , Ora Manish , Gambhir Sanjay
Published: May 2023

Follicular dendritic cell sarcoma (FDCS) is a low-grade sarcoma of mesenchymal dendritic cell origin, and it constitutes <0.4% of soft tissue sarcomas. We report a rare case of FDCS in a 32-year-old man. 18F-FDG PET/CT demonstrated the involvement of cervical, axillary, mediastinal, abdominal, and pelvic groups of lymph nodes and spleen. A cervical lymph node biopsy suggested FDCS. 18F-FDG PET/CT scan done after 3 cycles of chemotherapy (CHOP regime) revealed a complete metabolic response. This case presents the rarity of extensive presentation and complete response to the CHOP regime.
Kodamaea samutsakhonensis f.a., sp. nov., a novel ascomycetous yeast species isolated from wild mushrooms in Thailand
Authors: Nualthaisong Panadda , Sakolrak Baramee , Panicharoen Thitaya , Limtong Savitree , Khunnamwong Pannida
Published: May 2023

Two strains of genus Kodamaea, representing a novel anamorphic yeast species, were isolated from two samples of Marasmiellus sp. collected in Thailand. Analysis of the sequences of the internal transcribed spacer (ITS) regions and the D1/D2 domains of the large subunit (LSU) rRNA gene showed that the two strains differed by 27–42 nucleotide substitutions in the D1/D2 domains of the LSU rRNA gene and 7–34 nucleotide substitutions in the ITS region of a group of related species, Kodamaea smagusa CBS 11430T, Kodamaea fungicola JCM 10142T, Kodamaea plutei ATCC MYA-4329T, Kodamaea lidongshanica SD5S01T and Kodamaea jinghongensis NYNU 167162T. Phylogenetic analysis based on the concatenated sequences of the ITS and the D1/D2 domains of the LSU rRNA gene showed that the two strains were placed in the Kodamaea clade and clearly separated from other recognized species of the genus. Therefore, the two strains were assigned as a novel species of the genus Kodamaea, for which we propose the name Kodamaea samutsakhonensis f.a., sp. nov. The holotype is TBRC 16043T (=DMKU-BP19T) and the isotype is PYCC 9354. The MycoBank number of the novel species is MB 846490.
Comparison of machine-learning and logistic regression models to predict 30-day unplanned readmission: a development and validation study
Authors: Iwagami Masao , Inokuchi Ryota , Kawakami Eiryo , Yamada Tomohide , Goto Atsushi , Kuno Toshiki , Hashimoto Yohei , Michihata Nobuaki , Goto Tadahiro , Shinozaki Tomohiro , Sun Yu , Taniguchi Yuta , Komiyama Jun , Uda Kazuaki , Abe Toshikazu , Tamiya Nanako
Published: May 2023

We compared the predictive performance of gradient-boosted decision tree (GBDT), random forest (RF), deep neural network (DNN), and logistic regression (LR) with the least absolute shrinkage and selection operator (LASSO) for 30-day unplanned readmission, according to the number of predictor variables and presence/absence of blood-test results. We used electronic health records of patients discharged alive from 38 hospitals in 2015–2017 for derivation (n=339,513) and in 2018 for validation (n=118,074), including basic characteristics (age, sex, admission diagnosis category, number of hospitalizations in the past year, discharge location), diagnosis, surgery, procedure, and drug codes, and blood-test results. We created six patterns of datasets having different numbers of binary variables (that ≥5% or ≥1% of patients or ≥10 patients had) with and without blood-test results. For the dataset with the smallest number of variables (102), the c-statistic was highest for GBDT (0.740), followed by RF (0.734), LR-LASSO (0.720), and DNN (0.664). For the dataset with the largest number of variables (1543), the c-statistic was highest for GBDT (0.764), followed by LR-LASSO (0.755), RF (0.751), and DNN (0.720). We found that GBDT generally outperformed LR-LASSO, but the difference became smaller when the number of variables was increased and blood-test results were used.
Optimized sampling method for fecal microbiome and metabolome preservation under room temperature
Authors: Nomaguchi Tatsuhiro , Yamauchi Yohsuke , Nishimoto Yuichiro , Togashi Yuka , Ito Masaki , Salim Felix , Fujisawa Kota , Murakami Shinnosuke , Yamada Takuji , Fukuda Shinji
Published: May 2023

Background

The relationship among the human gut microbiome, microbially produced metabolites, and health outcomes remains of great interest. To decrease participant burden, room-temperature storage methods for fecal samples have become increasingly important. However, kits for storing the fecal microbiome and metabolome have not been well explored. We hypothesized that storing fecal samples by drying them with silica gel may be suitable.

Objectives

The objective was to evaluate the performance of storage at room temperature by drying feces for subsequent examination of the microbiome, microbial pathways, and the metabolome.

Methods

Feces from ten healthy adults (6 male and 4 female) were sampled and immediately processed, as controls, and stored at room temperature in an incubator, on an FTA card, in RNAlater, or dried by silica gel. Storage at room temperature continued for 7 days. Drying by the silica gel method was assessed for 14 days. The fecal microbiome was assessed by sequencing the bacterial 16S ribosomal RNA-encoding gene (V1-V2 region), fecal microbial pathway profiles were analyzed by whole-genome shotgun metagenomics, and fecal metabolome profiles were analyzed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS).

Results

Qualitative and β-diversity analyses of the microbiome, microbial pathways, and the metabolome showed that drying by silica gel were closest to those immediately after processing. When focusing on the abundances of individual microbes, microbial pathways, and metabolites, some were found to be significantly different. However, the intra-method ranking of individual items showed that 100%, 87-97%, and 63-76% of microbes, microbial pathways, and metabolites, respectively, were significantly correlated between silica gel preserving and immediately processing method.

Conclusions

The results showed that fecal sample drying could be effectively used for the preservation of the fecal microbiome and metabolome.
COVID-19 in meat plants: activation of a Target Prevention Plan, in Italy
Authors: Di Leone Giorgio , Bertinato Luigi , Brambilla Gianfranco , Manno Valerio , Napolano Flavio , Savi Simona , Settimo Gaetano , Lagravinese Domenico
Published: May 2023

During the COVID-19 pandemics, several outbreaks have been recorded all other the world in industrial slaughterhouses and meat processing plants. Occupational preventive medicine in such non-healthcare frontline essential services accounts for combined different environmental, social, and economic factors, to reduce the burden of COVID-19 in the workplaces and in the connected residential settings. In Italy, during the first year of the pandemics, an advocacy action has been activated, targeted on meat plant managers and related food business operators. A risk-oriented control plan was agreed by competent Italian Health Authorities at Region/Province level. A questionnaire focused on the inventoried risk factors reported in the literature in such working places have been developped as supporting tool, and administered on voluntary basis to the interested stakeholders. In addition, an outbreak questionnaire was proposed to the Prevention Depts of the Local Health Units. In the 2021 – 2022 years timeframe, we collected 333 advocacy and 24 outbreak questionnaires, respectively, on 4,765 inventoried plants at national level. Responses came mainly from those districts that locally activated the risk-oriented control plan. The lack of awareness to update the Risk Assessment Document of the meat plant for COVID-19, non instrumental body Temperature checks of workers at the entrance, working force from different subcontractors, poor hygiene in the shared places and insufficient ventilation represented the main critical points recorded. The cross-checks between the results from the advocacy and from the outbreak questionnaires are feeding an after-action review for such food-chain related essential work settings within a One Health approach.
A Yersinia effector activates JAK-STAT signaling in human macrophages
Authors: Berneking Laura , Bekere Indra , Schnapp Marie , Huang Jiabin , Ruckdeschel Klaus , Aepfelbacher Martin
Published: May 2023

The multifunctionalYersiniaeffector YopM inhibits effector triggered immunity and increases production of the anti-inflammatory cytokine Interleukin-10 (IL-10) to suppress the host immune response. Previously it was shown that YopM induces IL-10 gene expression by elevating phosphorylation of the serine-threonine kinase RSK1 in the nucleus of human macrophages. Using transcriptomics, we now show that YopM affects expression of genes encoding components of the JAK-STAT signaling pathway. Further analysis revealed that YopM mediates nuclear translocation of the transcription factor Stat3 inY. enterocoliticainfected macrophages and that knockdown of Stat3 inhibited YopM-induced IL-10 gene expression. YopM-induced Stat3 translocation did not depend on autocrine IL-10, activation of RSK1 or tyrosine phosphorylation of Stat3. Thus, besides activation of RSK1, stimulation of nuclear translocation of Stat3 is another mechanism by which YopM increases IL-10 gene expression in macrophages.
Body Shaming vs. Body Positivity: Exploring What Words Hurt and What Words Heal
Authors: Wansink Valerie , Wansink Brian
Published: May 2023

What can a health professional say to a bullied and body shamed child? This research elicited and categorized the words that were reported as being most memorably hurtful and helpful to 341 young people (79.5% female; average age 25.03 years) who had been body shamed. The most memorably hurtful comments generally involved either vivid comparisons or derogatory nicknames. Fortunately, the supportive words of health professionals, peers, and parents can heal. They include 1)reframing commentsthat redirect attention to positive features (such as feminine, healthy, etc.), 2)impact-related commentsthat emphasize how a physical feature influences or is admired by other people (such one’s eyes or smile that “lights up the room”), and 3)identity-related commentsthat redefine one’s physical identify or self-concept (such as striking or mesmerizing). Knowing the type of words that were helpful in healing can be useful to healthcare professionals as well as parents and peers.
Identification of pan-cancer/testis genes and validation of therapeutic targeting in triple-negative breast cancer: Lin28a- and Siglece-based vaccination induces anti-tumor immunity and inhibits metastasis
Authors: Carter Jason A. , Matta Bharati , Battaglia Jenna , Somerville Carter , Harris Benjamin D. , LaPan Margaret , Atwal Gurinder S. , Barnes Betsy J.
Published: May 2023

Background

Cancer-testis (CT) genes are targets for tumor antigen-specific immunotherapy given that their expression is normally restricted to the immune-privileged testis in healthy individuals with aberrant expression in tumor tissues. While they represent targetable germ-tissue antigens and play important functional roles in tumorigenesis, there is currently no standardized approach for identifying clinically relevant CT genes. Optimized algorithms and validated methods for accurate prediction of reliable CT antigens with high immunogenicity are also lacking.

Methods

Sequencing data from the Genotype-Tissue Expression (GTEx) and The Genomic Data Commons (GDC) databases was utilized for the development of a bioinformatic pipeline to identify CT exclusive genes. A CT germness score was calculated based on the number of CT genes expressed within a tumor type and their degree of expression. The impact of tumor germness with clinical outcome was evaluated using healthy GTEx and GDC tumor samples. We then used a triple-negative breast cancer mouse model to develop and test an algorithm that predicts epitope immunogenicity based on the identification of germline sequences with strong MHCI and MHCII binding affinities. Germline sequences for CT genes were synthesized as long synthetic peptide vaccines and tested in the 4T1 triple-negative model of invasive breast cancer with Poly(I:C) adjuvant. Vaccine immunogenicity was determined by flow cytometric analysis ofin vitroandin vivoT cell responses. Primary tumor growth and lung metastasis was evaluated by histopathology, flow cytometry and colony formation assay.

Results

We developed a new bioinformatic pipeline to reliably identify CT exclusive genes as immunogenic targets for immunotherapy. We identified CT genes that are exclusively expressed within the testis, lack detectable thymic expression, and are significantly expressed in multiple tumor types. High tumor germness correlated with tumor progression but not with tumor mutation burden, supporting CT antigens as appealing targets in low mutation burden tumors. Importantly, tumor germness also correlated with markers of anti-tumor immunity. Vaccination of 4T1 tumor bearing mice with Siglece and Lin28a antigens resulted in increased T cell anti-tumor immunity and reduced primary tumor growth and lung metastases.

Conclusion

Our results present a novel strategy for the identification of highly immunogenic CT antigens for the development of targeted vaccines that induce anti-tumor immunity and inhibit metastasis.
Molecular mechanisms for activation of the 26S proteasome
Authors: Lee Donghoon , Zhu Yanan , Colson Louis , Wang Xiaorong , Chen Siyi , Tkacik Emre , Huang Lan , Ouyang Qi , Goldberg Alfred L. , Lu Ying
Published: May 2023

Various hormones, kinases, and stressors (fasting, heat shock) stimulate 26S proteasome activity. To understand how its capacity to degrade ubiquitylated protein can increase, we studied ZFAND5, which promotes protein degradation during muscle atrophy. Cryo-electron microscopy showed that ZFAND5 induces large conformational changes in the 19S regulatory particle. ZFAND5’s AN1 Zn finger interacts with the Rpt5 ATPase and its C-terminus with Rpt1 ATPase and Rpn1, a ubiquitin-binding subunit. Surprisingly, these C-terminal interactions are sufficient to activate proteolysis. With ZFAND5 bound, entry into the proteasome’s protein translocation channel is wider, and ZFAND5 dissociation causes opening of the 20S gate for substrate entry. Using single-molecular microscopy, we showed that ZFAND5 binds ubiquitylated substrates, prolongs their association with proteasomes, and increases the likelihood that bound substrates undergo degradation, even though ZFAND5 dissociates before substrate deubiquitylation. These changes in proteasome conformation and reaction cycle can explain the accelerated degradation and suggest how other proteasome activators may stimulate proteolysis.
Equivalent physical dose (EPD) for improved precision in voxelized dosimetry
Authors: Abbott Elliot M. , Jones Bleddyn , Vojnovic Borivoj , Falzone Nadia , Turner Adam , Vallis Katherine A.
Published: May 2023

Purpose

Equivalent dose in 2 Gy fractions (EQD2), based on the original biological effective dose (BED) equation, is frequently used to guide treatment in the clinic. This work addresses the limitations of EQD2 in the context of voxelized dosimetry, clarifies potential sources of confusion, and provides an alternative formulation for improved precision.

Methods and Materials

The EQD2 formula was evaluated by a simple insertion of the EQD2 dose into the BED equation. The mathematically exact form of EQD2, referred to here as equivalent physical dose (EPD), was provided by solving the linear-quadratic model BED equation for dose using the quadratic formula. The EPD derivation was compared in terms of absolute error to the EQD2 derivation, which separates the Relative Effect term from the BED equation.

Results

The EQD2 expression implicitly assumed a homogenous dose, demonstrating that its use in voxelized dosimetry can mislead. As an alternative formulation, EPD was shown to adhere more closely to the first principles of radiobiological modeling. An error analysis identified absolute errors from EQD2 sometimes in excess of 10%.

Conclusions

Assumptions in the standard EQD2 equation are inappropriate in the context of voxelized dosimetry, where voxels within a structure, such as a target volume, may receive a dose that differs from the prescribed dose. Using EPD (or BED) instead of EQD2 would address these areas of confusion. Optimizing therapy according to biological properties in this way could provide enhanced and more reliable radiobiological input to radiotherapy treatment planning.
Distinct genetic liability profiles define clinically relevant patient strata across common diseases
Authors: Trastulla Lucia , Moser Sylvain , Jiménez-Barrón Laura T. , Andlauer Till F.M. , von Scheidt Moritz ,   Schizophrenia Working Group of the Psychiatric Genomics Consortium, Budde Monika , Heilbronner Urs , Papiol Sergi , Teumer Alexander , Homuth Georg , Falkai Peter , Völzke Henry , Dörr Marcus , Schulze Thomas G. , Gagneur Julien , Iorio Francesco , Müller-Myhsok Bertram , Schunkert Heribert , Ziller Michael J.
Published: May 2023

Genome-wide association studies have unearthed a wealth of genetic associations across many complex diseases. However, translating these associations into biological mechanisms contributing to disease etiology and heterogeneity has been challenging. Here, we hypothesize that the effects of disease-associated genetic variants converge onto distinct cell type specific molecular pathways within distinct subgroups of patients. In order to test this hypothesis, we develop the CASTom-iGEx pipeline to operationalize individual level genotype data to interpret personal polygenic risk and identify the genetic basis of clinical heterogeneity. The paradigmatic application of this approach to coronary artery disease and schizophrenia reveals a convergence of disease associated variant effects onto known and novel genes, pathways, and biological processes. The biological process specific genetic liabilities are not equally distributed across patients. Instead, they defined genetically distinct groups of patients, characterized by different profiles across pathways, endophenotypes, and disease severity. These results provide further evidence for a genetic contribution to clinical heterogeneity and point to the existence of partially distinct pathomechanisms across patient subgroups. Thus, the universally applicable approach presented here has the potential to constitute an important component of future personalized medicine concepts.
EphrinB2 knockdown in cervical spinal cord preserves diaphragm innervation in a mutant SOD1 mouse model of ALS
Authors: Urban Mark W. , Charsar Brittany A. , Heinsinger Nicolette M. , Markandaiah Shashirekha S. , Sprimont Lindsay , Zhou Wei , Brown Eric V. , Henderson Nathan T. , Thomas Samantha J. , Ghosh Biswarup , Cain Rachel E. , Trotti Davide , Pasinelli Piera , Wright Megan C. , Dalva Matthew B. , Lepore Angelo C.
Published: May 2023

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss. Importantly, non-neuronal cell types such as astrocytes also play significant roles in disease pathogenesis. However, mechanisms of astrocyte contribution to ALS remain incompletely understood. Astrocyte involvement suggests that transcellular signaling may play a role in disease. We examined contribution of transmembrane signaling molecule ephrinB2 to ALS pathogenesis, in particular its role in driving motor neuron damage by spinal cord astrocytes. In symptomatic SOD1G93Amice (a well-established ALS model), ephrinB2 expression was dramatically increased in ventral horn astrocytes. Reducing ephrinB2 in the cervical spinal cord ventral horn via viral-mediated shRNA delivery reduced motor neuron loss and preserved respiratory function by maintaining phrenic motor neuron innervation of diaphragm. EphrinB2 expression was also elevated in human ALS spinal cord. These findings implicate ephrinB2 upregulation as both a transcellular signaling mechanism in mutant SOD1-associated ALS and a promising therapeutic target.
Genome streamlining in CPR bacteria transitioning from soil to groundwater
Authors: Chaudhari Narendrakumar M. , Pérez-Carrascal Olga M. , Overholt Will A. , Totsche Kai U. , Küsel Kirsten
Published: May 2023

To better understand the influence of habitat on the genetic content of Candidate Phyla Radiation (CPR) bacteria, we studied the effects of transitioning from soil to groundwater on genomic divergences of these organisms. Bacterial metagenome-assembled genomes (318 total, 35 of CPR bacteria) were generated from seepage waters and compared directly to groundwater counterparts. Seepage water CPR bacteria exhibited 1.24-fold greater mean genome size, while their inferred mean replication rate was 21.1% lower than groundwater lineages. While exploring gene loss and adaptive gains in closely related lineages in groundwater, we identified a zinc transporter, a surface protein, and a lipogylcopeptide resistance gene unique to a seepage Parcubacterium. A nitrite reductase gene unique to the groundwater Parcubacterium, likely acquired from pelagic microbes via horizontal gene transfer, was also identified. Groundwater Parcubacteria harbored nearly double the fraction (9.4%) of pseudogenes than their seepage kin (4.9%), suggesting further genome streamlining.
PandoGen: Generating complete instances of future SARS-CoV-2 sequences using Deep Learning
Authors: Ramachandran Anand , Lumetta Steven S. , Chen Deming
Published: May 2023

One of the challenges in a viral pandemic is the emergence of novel variants with different phenotypical characteristics. An ability to forecast future viral individuals at the sequence level enables advance preparation by characterizing the sequences and closing vulnerabilities in current preventative and therapeutic methods. In this article, we explore, in the context of a viral pandemic, the problem of generating complete instances of undiscovered viral protein sequences, which have a high likelihood of being discovered in the future using protein language models. Current approaches to training these models fit model parameters to a known sequence set, which does not suit pandemic forecasting as future sequences differ from known sequences in some respects. To address this, we develop a novel method, called PandoGen, to train protein language models towards the pandemic protein forecasting task. PandoGen combines techniques such as synthetic data generation, conditional sequence generation, and reward-based learning, enabling the model to forecast future sequences, with a high propensity to spread. Applying our method to modeling the SARS-CoV-2 Spike protein sequence, we find empirically that our model forecasts twice as many novel sequences with five times the case counts compared to a model that is thirty times larger. Our method forecasts unseen lineages months in advance, whereas models 4× and 30× larger forecast almost no new lineages. When trained on data available up to a month before the onset of important Variants of Concern, our method consistently forecasts sequences belonging to those variants within tight sequence budgets.

PandoGen is available at:https://github.com/UIUC-ChenLab/PandoGen
YidC fromEscherichia coliforms an ion-conducting pore upon activation by ribosomes
Authors: Knyazev Denis G. , Winter Lukas , Vogt Andreas , Posch Sandra , Siligan Christine , Goessweiner-Mohr Nikolaus , Hagleitner-Ertugrul Nora , Koch Hans-Georg , Pohl Peter
Published: May 2023

The universally conserved protein YidC aids the insertion and folding of transmembrane polypeptides independently or as a part of the SecYEG translocon complex. In the former scenario, the lipid-exposed YidC surface equipped with a highly conserved positively charged arginine is thought to facilitate membrane insertion of the nascent chain by providing a countercharge for the acidic residues at the polypeptide’s N-terminal region. Here we show that the purified and reconstitutedE. coliYidC forms an ion-conducting transmembrane pore upon binding a ribosome or ribosome-nascent chain complex (RNC). This pore is closed in the absence of ribosomes. As this pore is not visible in the published monomeric YidC structure, we used AlphaFold to construct the model of a parallel YidC dimer. Experimental evidence for a dimeric assembly comes from our BN-PAGE analysis of native vesicles, fluorescence correlation spectroscopy studies, and single-molecule fluorescence microscopy. In the dimeric model, the conserved positively charged arginine and many residues interacting with nascent chains point into the putative pore. This result suggests the possibility of an alternative mode of YidC-assisted membrane protein insertion.