bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuroendocrine neoplasms of the orbit: report of three cases and a literature review
Authors: Qiao JunYi , Wang Yujiao , He Weimin
Published: September 2023

Neuroendocrine neoplasms (NENs) originate from neuroendocrine cells, and mainly occur in the gastrointestinal tract and lungs, rarely occurring in the orbit. Here, the clinicopathologic factors, treatments and prognosis of three cases of orbital NENs are described. The mean age of the three patients (two females and one male) was 59 years. Two cases exhibited ocular symptoms, including unilateral proptosis and eyelid mass, while the third case presented systemic symptoms exhibited as Cushing’s syndrome. The tumours were surgically resected in all three patients. Immunohistochemistry assays revealed positive expression for pan cytokeratin and epithelial membrane antigen in all cases. Additionally, neural cell adhesion molecule 1 (also known as CD56) and synaptophysin were positive in two cases. The pathological diagnosis for case 1 and 2 was ‘neuroendocrine carcinoma’ and both patients died three months after diagnosis. Case 3 was diagnosed with a neuroendocrine tumour and the symptoms of Cushing’s syndrome gradually improved following surgery. In addition, no recurrence was observed during the four-year follow-up period. These cases demonstrate that orbital neuroendocrine tumours show different clinical manifestations due to the different types. Pathology may clarify the diagnosis, classification and grading, and provide a reference value for treatment and prognosis.
Double-negative neuromyelitis optica spectrum disorder
Authors: Wu Yan , Geraldes Ruth , Juryńczyk Maciej , Palace Jacqueline
Published: September 2023

Most patients with neuromyelitis optica spectrum disorders (NMOSD) test positive for aquaporin-4 antibody (AQP4-IgG) or myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). Those who are negative are termed double-negative (DN) NMOSD and may constitute a diagnostic and therapeutic challenge. DN NMOSD is a syndrome rather than a single disease, ranging from a (postinfectious) monophasic illness to a more chronic syndrome that can be indistinguishable from AQP4-IgG+ NMOSD or develop into other mimics such as multiple sclerosis. Thus, underlying disease mechanisms are likely to be heterogeneous. This topical review aims to (1) reappraise antibody-negative NMOSD definition as it has changed over time with the development of the AQP4 and MOG-IgG assays; (2) outline clinical characteristics and the pathophysiological nature of this rare entity by contrasting its differences and similarities with antibody-positive NMOSD; (3) summarize laboratory characteristics and magnetic resonance imaging findings of DN NMOSD; and (4) discuss the current treatment for DN NMOSD.
The curious case of the realist trial: Methodological oxymoron or unicorn?
Authors: Nielsen Steffen Bohni , Jaspers Sofie Østergaard , Lemire Sebastian
Published: September 2023

Realist evaluation and experimental designs are both well-established approaches to evaluation. Over the past 10 years, realist trials—evaluations purposefully combining realist evaluation and experimental designs—have emerged. Informed by a comprehensive review of published realist trials, this article examines to what extent and how realist trials align with quality standards for realist evaluations and randomized controlled trials and to what extent and how the realist and trial aspects of realist trials are integrated. We identified only few examples that met high-quality standards for both experimental and realist studies and that merged the two designs.
The influence of information generation on destination memory
Authors: Pinto Raquel , Albuquerque Pedro B
Published: September 2023

To remember to whom we transmit information, we rely on destination memory, with worse performance occurring when participants share personal facts (e.g., my age is . . .) compared with interesting ones (e.g., a shrimp’s heart is in its head). When reporting personal information, the internal attentional focus decreases the attentional resources available to associate that information with recipients, resulting in worse destination memory. Given that the poorer destination memory when participants transmitted personal facts was always compared with the transmission of interesting facts, in Experiment 1 (between-participants design: 41 participants) and Experiment 2 (within-participants design: 30 participants), we compared the generation and transmission of personal facts with the transmission of familiar proverbs. Again, the generation and transmission of personal facts hampered destination memory. Besides the type of information (personal vs. familiar proverbs), the conditions differed regarding the type of process (generation vs. transmission of information). To clarify the influence of generation on destination memory, in Experiment 3 ( N = 31), participants (1) transmitted and (2) generated and transmitted familiar proverbs, and significant differences in destination memory between the conditions was not observed. In general, our experiments seem to support the assumption that transmitting personal information leads to worse destination memory not because participants generated the information but because personal facts drive the attentional focus to the self.
Threat Appraisal and Pediatric Anxiety: Proof of Concept of a Latent Variable Approach
Authors: Bernstein Rachel A. , Smith Ashley R. , Kitt Elizabeth R. , Cardinale Elise M. , Harrewijn Anita , Abend Rany , Michalska Kalina J. , Pine Daniel S. , Kircanski Katharina
Published: September 2023

Elevated threat appraisal is a postulated neurodevelopmental mechanism of anxiety disorders. However, laboratory-assessed threat appraisals are task-specific and subject to measurement error. We used latent-variable analysis to integrate youths’ self-reported threat appraisals across different experimental tasks; we next examined associations with pediatric anxiety and behavioral- and psychophysiological-task indices. Ninety-two youths ages 8 to 17 ( M = 13.07 years, 65% female), including 51 with a primary anxiety disorder and 41 with no Axis I diagnosis, completed up to eight threat-exposure tasks. Anxiety symptoms were assessed using questionnaires and ecological momentary assessment. Appraisals both before and following threat exposures evidenced shared variance across tasks. Derived factor scores for threat appraisal were associated significantly with anxiety symptoms and variably with task indices; findings were comparable with task-specific measures and had several advantages. Results support an overarching construct of threat appraisal linked with pediatric anxiety, providing groundwork for more robust laboratory-based measurement.
Health Education for Chronic Kidney Disease Patients Not on Dialysis Through the Pictorial Patient Information Leaflet
Authors: Sirimalla Shivaprasad , Mateti Uday Venkat , Shenoy Pradeep , Shetty Shraddha
Published: September 2023

Background: Educating the patient with patient information leaflets is helpful to increase understanding and awareness about chronic kidney disease. Various educational materials are available online, but their quality is mixed. The content was found to be unreliable or incomprehensible. Objective: The study aimed to develop, validate, test the readability, translation, and design of the patient information leaflet and focused on assessing patients’ knowledge levels using questionnaires after providing the validated patient information leaflet. Methods: A prospective study was conducted among chronic kidney disease patients who were not on dialysis. The patient information leaflet was prepared based on experts’ opinions and a thorough review of various resources. Experts validated the content of the patient information leaflet through the content validity index. After being validated, the Baker Able leaflet design scale was used to evaluate the layout and design. Knowledge assessment questions were validated using item-content validity index scores to assess patient knowledge before and after providing the patient information leaflet. Results: A total of 60 randomly selected chronic kidney disease patients were enrolled. The content validity index of the patient information leaflet was found to be 0.9. The Baker Able leaflet design score was found to be 25. Knowledge was assessed and it showed that score had increased from 42 ± 6.95 to 73.5 ± 6.70, respectively, with a P-value <0.000. Conclusion: This study concluded that the patient information leaflet was developed based on standard procedures. Significant improvement was seen in patients’ knowledge after utilizing a validated patient information leaflet.
Medical experience as an influencing parameter in emergency medical care for psychiatric emergencies: retrospective analysis of a multicenter survey
Authors: Schick Benedikt , Mayer Benjamin , Hensel Constanze , Schmid Sebastian , Jungwirth Bettina , Barth Eberhard , Muth Claus-Martin , Katzenschlager Stephan , Schönfeldt-Lecuona Carlos
Published: September 2023

Background

Prehospital care of psychiatric patients often relies on the medical experience of prehospital emergency physicians (PHEPs). The psychiatrists (PSs) involved in the further treatment of psychiatric patients also often rely on their experience. Furthermore, the interaction between PHEPs and PSs is characterized by interaction problems and different approaches in the prehospital care of the psychiatric emergency.

Objectives

To analyze the phenomenon of “medical experience” as a cause of possible interaction-related problems and assess its impact on the prehospital decision-making process between prehospital emergency physicians and psychiatrists.

Methods

The retrospective data analysis was conducted between November 2022 and March 2023. Medical experience was defined as follows, based on the demographic information collected in the questionnaires: For PHEPs, the period since obtaining the additional qualification in emergency medicine was defined as a surrogate marker of medical experience: (i) inexperienced: < 1 year, (ii) experienced: 1–5 years, (iii) very experienced: > 5 years. For PSs, age in years was used as a surrogate parameter of medical experience: (i) inexperienced: 25–35 years, (ii) experienced: 35–45 years, (iii) very experienced: > 45 years.

Results

Inexperienced PSs most frequently expressed anxiety about the psychiatric emergency referred by a PHEP (27.9%). Experienced PHEPs most frequently reported a lack of qualifications in handling the care of psychiatric emergencies (p = 0.002). Very experienced PHEPs were significantly more likely to have a referral refused by the acute psychiatric hospital if an inexperienced PS was on duty (p = 0.01). Experienced PHEPs apply an intravenous hypnotic significantly more often (almost 15%) than PSs of all experience levels (p = 0.001). In addition, very experienced PHEPs sought prehospital phone contact with acute psychiatry significantly more often (p = 0.01).

Conclusion

PHEPs should be aware that the PS on duty may be inexperienced and that treating emergency patients may cause him/her anxiety. On the other hand, PHEPs should be receptive to feedback from PS who have identified a qualification deficiency in them. Jointly developed, individualized emergency plans could lead to better prehospital care for psychiatric emergency patients. Further training in the prehospital management of psychiatric disorders is needed to minimize the existing skills gap among PHEPs in the management of psychiatric disorders.
Effect of Empagliflozin and Pioglitazone on left ventricular function in patients with type two diabetes and nonalcoholic fatty liver disease without established cardiovascular disease: a randomized single-blind clinical trial
Authors: Attaran Fereshte , Emami Sepideh , Sohrabi Masoudreza , Malek Mojtaba , Ajdarkosh Hossein , Khoonsari Mahmoodreza , Ismail-Beigi Faramarz , Khamseh Mohammad E.
Published: September 2023

Background

Nonalcoholic fatty liver disease (NAFLD) is a complex metabolic disorder that increases the risk for cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Global longitudinal strain (GLS) is an indicator of left ventricular (LV) mechanics and can detect subclinical myocardial dysfunction. We compared the effects of pioglitazone and empagliflozin on GLS in patients with T2DM and NAFLD without established atherosclerotic cardiovascular disease.

Methods

This study was a 24-week randomized, single-blind, and parallel-group (1: 1 ratio) clinical trial. Seventy-three participants with T2DM (being treated with metformin) and NAFLD but without established atherosclerotic cardiovascular disease (ASCVD) were randomized to empagliflozin or pioglitazone. Liver steatosis and fibrosis were measured using transient elastography, and GLS was measured by echocardiography. The primary endpoint was the change in GLS from baseline to week 24. Secondary end points include changes in controlled attenuation parameter (CAP) and Liver stiffness measure (LSM).

Results

In this study, GLS improved by 1.56 ± 2.34% (P < 0.01) in the pioglitazone group and 1.06 ± 1.83% (P < 0.01) in the empagliflozin group without a significant difference between the two groups (P = 0.31). At baseline, GLS was inversely associated with the severity of liver fibrosis: r = − 0.311, P = 0.007. LSM in the pioglitazone and empagliflozin group [(-0.73 ± 1.59) and (-1.11 ± 1.33)] kpa (P < 0.01) decreased significantly. It was without substantial difference between the two groups (P = 0.26). Empagliflozin and pioglitazone both improved controlled attenuation parameter. The improvement was more critical in the empagliflozin group: -48.22 + 35.02 dB/m vs. -25.67 + 41.50 dB/m, P = 0.01.

Conclusion

Subclinical cardiac dysfunction is highly important in patients with T2DM and with NAFLD. Empagliflozin and Pioglitazone improve LV mechanics and fibrosis in patients without established ASCVD. This has a prognostic importance on cardiovascular outcomes in high-risk patients with T2DM. Moreover, empagliflozin ameliorates liver steatosis more effectively them pioglitazone. This study can serve as a start point hypothesis for the future. Further studies are needed to explore the concept in larger populations.

Trial registration

: This trial was registered in the Iranian Registry of Clinical Trials (IRCT): “A Comparison between the Effect of Empagliflozin and Pioglitazone on Echocardiographic Indices in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease” IRCT20190122042450N5, 29 November 2020. https://www.irct.ir/search/result?query=IRCT20190122042450N5.
Rupture of 40-year-old silicone gel breast implants: a case report
Authors: Wu Hsin-Hsuan , Weng Yu-Tse , Chou Yu-Yu , Wang Chih-Hsin
Published: September 2023

Background

Implant rupture is one of the complications of breast augmentation surgery. The rupture of silicone implants is often insidious, potentially causing problems at any time. This is a case report of the rupture of 145-cc breast implants manufactured by Dow Corning Corporation and their removal at 40 years after augmentation.

Case Presentation

A 70-year-old female patient was admitted for the removal of a lump in the upper and inner quadrants of the right breast. After a detailed examination, a rupture of the bilateral breast implants was diagnosed. Explantation without replacement was performed; the entire procedure proceeded smoothly. Immunohistochemical staining revealed siliconoma with lymphoid hyperplasia and calcification in the bilateral breasts with no signs of malignancy.

Conclusions

Silicone breast augmentation is one of the most popular aesthetic surgical procedures worldwide. Therefore, it is important to educate patients on the need for close monitoring of their implants after augmentation through magnetic resonance imaging or ultrasound to facilitate early detection of any changes before a rupture occurs. Early detection of the implant rupture, in turn, will facilitate early and effective management.
Racial disparities in adequacy of prenatal care during the COVID-19 pandemic in South Carolina, 2018–2021
Authors: Julceus Emmanuel Fabrice , Olatosi Bankole , Hung Peiyin , Zhang Jiajia , Li Xiaoming , Liu Jihong
Published: September 2023

Background

During the COVID-19 pandemic, hospitals’ decision of not admitting pregnant women’s partner or support person, and pregnant women’s fear of contracting COVID-19 in hospitals may disrupt prenatal care. We aimed to examine whether prenatal care utilization in South Carolina varied before and during the COVID-19 pandemic, and whether the variation was different by race.

Methods

We utilized 2018–2021 statewide birth certificate data using a pre-post design, including all women who delivered a live birth in South Carolina. The Kotelchuck Index - incorporating the timing of prenatal care initiation and the frequency of gestational age-adjusted visits - was employed to categorize prenatal care into inadequate versus adequate care. Self-reported race includes White, Black, and other race groups. Multiple logistic regression models were used to calculate adjusted odds ratio of inadequate prenatal care and prenatal care initiation after first trimester by maternal race before and during the pandemic.

Results

A total of 118,925 women became pregnant before the pandemic (before March 2020) and 29,237 women during the COVID-19 pandemic (March 2020 – June 2021). Regarding race, 65.2% were White women, 32.0% were Black women and 2.8% were of other races. Lack of adequate prenatal care was more prevalent during the pandemic compared to pre-pandemic (24.1% vs. 21.6%, p < 0.001), so was the percentage of initiating prenatal care after the first trimester (27.2% vs. 25.0%, p < 0.001). The interaction of race and pandemic period on prenatal care adequacy and initiation was significant. The odds of not receiving adequate prenatal care were higher during the pandemic compared to before for Black women (OR 1.26, 95% CI 1.20–1.33) and White women (OR 1.10, 95% CI 1.06–1.15). The odds of initiating prenatal care after the first trimester were higher during the pandemic for Black women (OR 1.18, 95% CI 1.13–1.24) and White women (OR 1.09, 95% CI 1.04–1.13).

Conclusions

Compared to pre-pandemic, the odds of not receiving adequate prenatal care in South Carolina was increased by 10% for White women and 26% for Black women during the pandemic, highlighting the needs to develop individual tailored interventions to reverse this trend.
Korean women’s perceptions of traumatic childbirth: a qualitative descriptive study
Authors: Yeo Jung Hee , Sagong Hae
Published: September 2023

Background

Previous studies have established that negative or traumatic childbirth can create childbirth-related post-traumatic stress disorder (CB-PTSD). Because of the negative implications of CB-PTSD for mothers, children, and families, global qualitative research on traumatic or negative childbirth has risen in recent years. However, few studies have been conducted in South Korea. This study aims to explore women’s various perceptions of traumatic childbirth in South Korea.

Methods

This qualitative descriptive study examined nine women who were at high risk of PTSD (IES-R-K > 24) at the time of the interview, between 1 and 11 years after childbirth. Semi-structured interviews were conducted. Interview transcripts were subjected to thematic analysis.

Results

The analysis identified two themes with six subthemes, as follows: (1) person-centred factors (pain, guilt, maternal identity conflict, and damaged femininity); (2) society-centred factors (threatened dignity and disrupted relationships). These findings may be attributed to Korean culture (excessive motherhood and lookism), as well as unbearable pain, disrespectful childbirth environments, lack of spouse’s support, loss of their lifestyle, and unrealistic expectations.

Conclusions

This study demonstrates various negative consequences, ranging from psychological damage to conflict in women’s relationships with their spouses, and others. This highlights the various perceptions stemming from traumatic childbirth and emphasizes the significance of clinical intervention. Therefore, healthcare professionals’ greater understanding of women’s perceptions and increased concern about childbirth and respectful childbirth environments are required. In addition, based on our findings, there is a need to develop interventions that can alleviate CB-PTSD and further improve women’s mental health, particularly through women-centred interventions.
Association of stress on eating competence in mothers during pregnancy and six months postpartum
Authors: Sara Ghasem Pour , Ryesa Mansoor , Muzayyana Akhmadjonova , Myles S. Faith , Leah Lipsky , Tonja Nansel , Kyle S. Burger , Siega-Riz Anna Maria , Shearrer E. Grace
Published: September 2023

Background

Perceived stress is related to poor diet quality and unhealthy dietary patterns in women of reproductive age. Eating competence represents a variety of contextual skills reflecting a comfortable and flexible approach to eating and is associated with diet quality and health related behavior. In non-pregnant samples, perceived stress is negatively associated with eating competence. Given that pregnancy and the postpartum period can be periods of high stress, we hypothesized that higher stress in pregnancy would result in lower pregnancy eating competence.

Methods

Women (n = 296, mean BMIbaseline pregnancy = 26.3 ± SD 6.0) in the Pregnancy Eating Attributes Study (PEAS) were recruited from the Chapel Hill, North Carolina area. Perceived stress was assessed using the Perceived Stress Scale and eating competence using the ecSatter Inventory at their first trimester and 6-month postpartum visits. We used a mixed effect model to assess the effect of stress by time on eating competence, controlling for baseline pregnancy BMI, race and ethnicity, poverty to income ratio, and WIC status.

Results

Perceived stress was negatively associated with eating competence (b= -0.23, SE = 0.06, p < 0.001). The interaction of stress by time was negatively associated with eating competence (b = -0.15, SE = 0.08, p = 0.03), indicating that the association of stress with eating competence was stronger in postpartum than in pregnancy.

Conclusions

Perceived stress may adversely impact eating competence during both pregnancy and postpartum. Future studies intervening upon stress or eating competence during pregnancy and postpartum may inform potential causal relations.
Establishing a prognostic model based on immune-related genes and identification of BIRC5 as a potential biomarker for lung adenocarcinoma patients
Authors: Ren Qianhe , Li Qifan , Shao Chenye , Zhang Pengpeng , Hu Zhuangzhuang , Li Jun , Wang Wei , Yu Yue
Published: September 2023

Background

Lung adenocarcinoma (LUAD) is an extraordinarily malignant tumor, with rapidly increasing morbidity and poor prognosis. Immunotherapy has emerged as a hopeful therapeutic modality for lung adenocarcinoma. Furthermore, a prognostic model (based on immune genes) can fulfill the purpose of early diagnosis and accurate prognostic prediction.

Methods

Immune-related mRNAs (IRmRNAs) were utilized to construct a prognostic model that sorted patients into high- and low-risk groups. Then, the prediction efficacy of our model was evaluated using a nomogram. The differences in overall survival (OS), the tumor mutation landscape, and the tumor microenvironment were further explored between different risk groups. In addition, the immune genes comprising the prognostic model were subjected to single-cell RNA sequencing to investigate the expression of these immune genes in different cells. Finally, the functions of BIRC5 were validated through in vitro experiments.

Results

Patients in different risk groups exhibited sharply significant variations in OS, pathway activity, immune cell infiltration, mutation patterns, and immune response. Single-cell RNA sequencing revealed that the expression level of BIRC5 was significantly high in T cells. Cell experiments further revealed that BIRC5 knockdown markedly reduced LUAD cell proliferation.

Conclusion

This model can function as an instrumental variable in the prognostic, molecular, and therapeutic prediction of LUAD, shedding new light on the optimal clinical practice guidelines for LUAD patients.
Vaccine promotion strategies in community pharmacy addressing vulnerable populations: a scoping review
Authors: Chadi Alexandre , Thirion Daniel J. G. , David Pierre-Marie
Published: September 2023

Context

Social determinants of health are drivers of vaccine inequity and lead to higher risks of complications from infectious diseases in under vaccinated communities. In many countries, pharmacists have gained the rights to prescribe and administer vaccines, which contributes to improving vaccination rates. However, little is known on how they define and target vulnerable communities.

Objective

The purpose of this study is to describe how vulnerable communities are targeted in community pharmacies.

Methods

We performed a systematic search of the Embase and MEDLINE database in August 2021 inspired by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols (PRISMA ScR). Articles in English, French or Spanish addressing any vaccine in a community pharmacy context and that target a population defined as vulnerable were screened for inclusion.

Results

A total of 1039 articles were identified through the initial search, and 63 articles met the inclusion criteria. Most of the literature originated from North America (n = 54, 86%) and addressed influenza (n = 29, 46%), pneumococcal (n = 14, 22%), herpes zoster (n = 14, 22%) or human papilloma virus vaccination (n = 14, 22%). Lifecycle vulnerabilities (n = 48, 76%) such as age and pregnancy were most often used to target vulnerable patients followed by clinical factors (n = 18, 29%), socio-economical determinants (n = 16, 25%) and geographical vulnerabilities (n = 7, 11%). The most frequently listed strategy was providing a strong recommendation for vaccination, promotional posters in pharmacy, distributing leaflet/bag stuffers and providing staff training. A total of 24 barriers and 25 facilitators were identified. The main barriers associated to each vulnerable category were associated to effective promotional strategies to overcome them.

Conclusion

Pharmacists prioritize lifecycle and clinical vulnerability at the expense of narrowing down the definition of vulnerability. Some vulnerable groups are also under targeted in pharmacies. A wide variety of promotional strategies are available to pharmacies to overcome the specific barriers experienced by various groups.
“The pandemic only gave visibility to what is invisible”: a qualitative analysis of structural violence during COVID-19 and impacts on gender-based violence in Brazil
Authors: Vahedi Luissa , McNelly Samantha , Lukow Nina , Fonseca Anna Carolina , Erskine Dorcas , Poulton Catherine , Stark Lindsay , Seff Ilana
Published: September 2023

Background

The COVID-19 pandemic produced alarming rates of disease and mortality globally, yet few nations were as severely impacted as Brazil. The pandemic also exposed and exacerbated persistent forms of structural violence across Brazil, which complicated gender-based violence (GBV) prevention and response efforts. While structural violence is not new, the systemic pressure and uncertainty introduced by COVID-19 intensified the detrimental impact of structural violence on the lives of Brazilians impacted by GBV. This work qualitatively investigated how the COVID-19 pandemic amplified structural violence and GBV in Brazil.

Methods

We analyzed key informant interviews (KII) conducted with 12 service providers working in sectors related GBV prevention and response in Roraima, Boa Vista, and Rio de Janeiro. Interviews were audio-recorded, transcribed, and translated from Portuguese or Spanish into English, before applying deductive and inductive coding approaches through a collaborative data reduction process. The theoretical lens of structural violence outlined by Farmer and Rylko-Bauer guided the thematic development.

Results

Analyses identified three themes. First, structural violence manifests as policies of inaction and erasure, which reduce the opportunity for upward social mobility among GBV survivors including Black women, trans persons, and people who live in the favelas. Policies of inaction and erasure fail to acknowledge/adequately respond to the significant health and safety needs of these communities. Second, structural violence is a fundamental cause of violence against women and children. Finally, service providers described community driven responses that address the dire survival needs (i.e., food insecurity) imposed by COVID-19, within a context of structural violence. These community driven responses were innovative, agile, and based on dire needs expressed to, and observed by, the service providers interviewed.

Conclusion

This analysis highlights how the COVID-19 pandemic exacerbated existing forms of structural violence prevalent throughout Brazil. Findings stress the urgency with which the Brazilian government and international organization must act to support community driven programs that strive to address the most basic human needs.
Intranasal administration with recombinant vaccine PRVXJ-delgE/gI/TK-S induces strong intestinal mucosal immune responses against PDCoV
Authors: Huang Bingzhou , Huang Yao , Deng Lishuang , Xu Tong , Jian Zhijie , Lai Siyuan , Ai Yanru , Zhu Ling , Xu Zhiwen
Published: September 2023

Porcine deltacoronavirus (PDCoV) is a novel coronavirus that causes enteric diseases in pigs leading to substantial financial losses within the industry. The absence of commercial vaccines and limited research on PDCoV vaccines presents significant challenges. Therefore, we evaluated the safety and immunogenicity of recombinant pseudorabies virus (PRV) rPRVXJ-delgE/gI/TK-S through intranasal mucosal immunization in weaned piglets and SPF mice. Results indicated that rPRVXJ-delgE/gI/TK-S safely induced PDCoV S-specific and PRV gB-specific antibodies in piglets, with levels increasing 7 days after immunization. Virus challenge tests demonstrated that rPRVXJ-delgE/gI/TK-S effectively improved piglet survival rates, reduced virus shedding, and alleviated clinical symptoms and pathological damage. Notably, the recombinant virus reduced anti-inflammatory and pro-inflammatory responses by regulating IFN-γ, TNF-α, and IL-1β secretion after infection. Additionally, rPRVXJ-delgE/gI/TK-S colonized target intestinal segments infected with PDCoV, stimulated the secretion of cytokines by MLVS in mice, stimulated sIgA secretion in different intestinal segments of mice, and improved mucosal immune function. HE and AB/PAS staining confirmed a more complete intestinal mucosal barrier and a significant increase in goblet cell numbers after immunization. In conclusion, rPRVXJ-delgE/gI/TK-S exhibits good immunogenicity and safety in mice and piglets, making it a promising candidate vaccine for PDCoV.
CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of AEC2s
Authors: Sun Jianhui , Zhang Huacai , Liu Di , Liu Wenyi , Du Juan , Wen Dalin , Li Luoxi , Zhang Anqiang , Jiang Jianxin , Zeng Ling
Published: September 2023

Background

Functional alveolar regeneration is essential for the restoration of normal lung homeostasis after acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Lung is a relatively quiescent organ and a variety of stem cells are recruited to participate in lung repair and regeneration after lung tissue injury. However, there is still no effective method for promoting the proliferation of endogenous lung stem cells to promote repair and regeneration.

Methods

Using protein mass spectrometry analysis, we analyzed the microenvironment after acute lung injury. RNA sequencing and image cytometry were used in the alveolar epithelial type 2 cells (AEC2s) subgroup identification. Then we used Sftpc+AEC2 lineage tracking mice and purified AEC2s to further elucidate the molecular mechanism by which CTGF regulates AEC2s proliferation both in vitro and in vivo. Bronchoalveolar lavage fluid (BALF) from thirty ARDS patients who underwent bronchoalveolar lavage was collected for the analysis of the correlation between the expressing of Krt5 in BALF and patients’ prognosis.

Results

Here, we elucidate that AEC2s are the main facultative stem cells of the distal lung after ALI and ARDS. The increase of connective tissue growth factor (CTGF) in the microenvironment after ALI promoted the proliferation of AEC2s subpopulations. Proliferated AEC2s rapidly expanded and differentiated into alveolar epithelial type 1 cells (AEC1s) in the regeneration after ALI. CTGF initiates the phosphorylation of LRP6 by promoting the interaction between Krt5 and LRP6 of AEC2s, thus activating the Wnt signaling pathway, which is the molecular mechanism of CTGF promoting the proliferation of AEC2s subpopulation.

Conclusions

Our study verifies that CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of AEC2s subpopulation.
Phosphoflow cytometry to assess cytokine signaling pathways in peripheral immune cells: potential for inferring immune cell function and treatment response in patients with solid tumors
Authors: Toney Nicole J. , Schlom Jeffrey , Donahue Renee N.
Published: September 2023

Tumor biopsy is often not available or difficult to obtain in patients with solid tumors. Investigation of the peripheral immune system allows for in-depth and dynamic profiling of patient immune response prior to and over the course of treatment and disease. Phosphoflow cytometry is a flow cytometry‒based method to detect levels of phosphorylated proteins in single cells. This method can be applied to peripheral immune cells to determine responsiveness of signaling pathways in specific immune subsets to cytokine stimulation, improving on simply defining numbers of populations of cells based on cell surface markers. Here, we review studies using phosphoflow cytometry to (a) investigate signaling pathways in cancer patients’ peripheral immune cells compared with healthy donors, (b) compare immune cell function in peripheral immune cells with the tumor microenvironment, (c) determine the effects of agents on the immune system, and (d) predict cancer patient response to treatment and outcome. In addition, we explore the use and potential of phosphoflow cytometry in preclinical cancer models. We believe this review is the first to provide a comprehensive summary of how phosphoflow cytometry can be applied in the field of cancer immunology, and demonstrates that this approach holds promise in exploring the mechanisms of response or resistance to immunotherapy both prior to and during the course of treatment. Additionally, it can help identify potential therapeutic avenues that can restore normal immune cell function and improve cancer patient outcome.
Efficacy of the latest new stimulation patterns of spinal cord stimulation for intractable neuropathic pain compared to conventional stimulation: study protocol for a clinical trial
Authors: Tanei Takafumi , Maesawa Satoshi , Nishimura Yusuke , Nagashima Yoshitaka , Ishizaki Tomotaka , Ando Masahiko , Kuwatsuka Yachiyo , Hashizume Atsushi , Kurasawa Shimon , Saito Ryuta
Published: September 2023

Background

Spinal cord stimulation (SCS) is one of the neuromodulation therapies for chronic neuropathic pain. The conventional paresthesia-based SCS involves the application of tonic stimulation that induces a sense of paresthesia. Recently, new SCS stimulation patterns without paresthesia have been developed. Differential target multiplexed (DTM) stimulation and fast-acting subperception therapy (FAST) stimulation are the latest paresthesia-free SCS patterns.

Methods

A single-center, open-label, crossover, randomized clinical trial to investigate the superiority of SCS using the latest new stimulation patterns over conventional tonic stimulation for neuropathic pain is planned. This study consists of two steps: SCS trial (first step) and SCS system implantation (second step). In the SCS trial, participants will be randomly assigned to 4 groups receiving stimulation, including tonic, DTM, and FAST. Each stimulation will then be performed for 2 days, and a visual analog scale (VAS) for pain will be evaluated before and after each stimulation pattern. A stimulation-off period for 1 day is set between each stimulation pattern to wash out the residual previous stimulation effects. Pain improvement is defined as more than 33% reduction in the pain VAS. The primary analysis will compare pain improvement between the new stimulation patterns and the conventional tonic stimulation pattern in the SCS trial. The secondary outcomes will be evaluated as follows: (1) the relationships between causative disease and improvement rate by each stimulation pattern; (2) comparison of pain improvement between the DTM and FAST stimulation patterns in all cases and by causative disease; (3) changes in assessment items preoperatively to 24 months after the implantation; (4) preoperative factors associated with long-term effects defined as continuing for more than 12 months; and (5) adverse events related to this study 3 months after the implantation.

Discussion

This study aims to clarify the effectiveness of the latest new stimulation patterns compared to the conventional tonic stimulation. In addition, which stimulation pattern is most effective for which kind of causative disease will be clarified.

Trial registration

Japan Registry of Clinical Trials (jRCT) 1,042,220,094. Registered on 21 November 2022, and last modified on 6 January 2023. jRCT is an approved member of the Primary Registry Network of WHO ICTRP.
Enzymatic synthesis of novel pyrrole esters and their thermal stability
Authors: Hu Jingyi , Zhou Meng , Zhang Yujie , Zhang Xi , Ji Xiaoming , Zhao Mingqin , Lai Miao
Published: September 2023

In the present work a simple enzymatic approach (Novozym 435) for transesterification to synthesize pyrrole esters was reported. To generate the best reaction conditions, which resulted in the optimum yield of 92%, the effects of lipase type, solvent, lipase load, molecular sieves, substrate molar ratio of esters to alcohol, reaction temperature, reaction duration, and speed of agitation were evaluated. The range of alcohols was assessed under optimal circumstances. The spectrum observations conclusively demonstrated that the compounds could be generated with high yield under the circumstances utilized for synthesis. The odor characteristics of the pyrrolyl esters obtained were examined by gas chromatography–mass spectrometry-olfactometry (GC–MS–O). Among them, compounds of benzhydryl 1H-pyrrole-2-carboxylate (3j), butyl 1H-pyrrole-2-carboxylate (3k) and pentyl 1H-pyrrole-2-carboxylate (3l) present sweet and acid aroma. In addition, the thermal degradation process was further studied using the Py–GC/MS (pyrolysis–gas chromatography/mass spectrometry), TG (thermogravimetry), and DSC (differential scanning calorimeter) techniques. The outcomes of the Py–GC/MS, TG, and DSC techniques show that they have excellent thermal stability.
Schistosoma japonicum EKLF/KLF1 is a potential immune target to tackle schistosomiasis
Authors: Piao Xianyu , Jiang Ning , Liu Shuai , Duan Jiamei , dai Hang , Hou Nan , Chen Qijun
Published: September 2023

Background

Interruption of parasite reproduction by targeting migrating schistosomula is a promising strategy for managing schistosomiasis. Hepatic schistosomula proteins previously identified based on second-generation schistosome DNA sequencing were found to hold excellent potential for schistosomiasis japonica diagnosis and as vaccine candidates. However, there are still many unknown schistosomula proteins that warrant further investigations. Herein, a novel schistosomula protein, the Schistosoma japonicum erythroid Krüppel-like factor (SjEKLF/KLF1), was explored.

Methods

Sequence alignment was carried out to detect the amino acid sequence characteristics of SjEKLF. The expression profile of SjEKLF was determined by western blot and immunofluorescence analysis. Enzyme-linked immunosorbent assay was used to determine the antigenicity of SjEKLF in hosts. Mice immunised with recombinant SjEKLF were challenged to test the potential value of the protein as an immunoprotective target.

Results

SjEKLF is defined as EKLF/KLF1 for its C-terminal DNA-binding domain. SjEKLF is mainly expressed in hepatic schistosomula and male adults and located within the intestinal intima of the parasites. Notably, high levels of SjEKLF-specific antibodies were detected in host sera and SjEKLF exhibited outstanding sensitivity and specificity for schistosomiasis japonica immunodiagnosis but failed to distinguish between ongoing infection and previous exposure. In addition, SjEKLF immunisation reduced the infection in vivo, resulting in decreased worm and egg counts, and alleviated body weight loss and hepatomegaly in infected mice.

Conclusions

Overall, these findings demonstrate that SjEKLF is critical for the infection of S. japonicum and may be a potential target to help control S. japonicum infection and transmission.

Graphical Abstract
What can the citations of systematic reviews of ethical literature tell us about their use?—an explorative empirical analysis of 31 reviews
Authors: Nobile Hélène , Moshtaghin Natali Lilie Randjbar , Lüddecke Zoë , Schnarr Antje , Mertz Marcel
Published: September 2023

Background

Systematic reviews of ethical literature (SREL) aim at providing an overview of ethical issues, arguments, or concepts on a specific ethical topic. As SREL are becoming more common, their methodology and possible impact are increasingly subjected to critical considerations. Because they analyse and synthetise normative literature, SREL are likely to be used differently than typical systematic reviews. Still, the uses and the expected purposes of SREL were, to date, mainly theoretically discussed. Our explorative study aimed at gaining preliminary empirical insights into the actual uses of SREL.

Methods

Citations of SREL in publications, both scientific and non-scientific, were taken as proxy for SREL uses. The citations of 31 published SREL were systematically searched on Google Scholar. Each citation was qualitatively analysed to determine its function. The resulting categorisation of SREL citations was further quantitatively investigated to unveil possible trends.

Results

The analysis of the resulting sample of SREL citations (n=1812) showed that the selected SREL were mostly cited to support claims about ethical issues, arguments, or concepts, but also to merely mention the existence of literature on a given topic. In this sample, SREL were cited predominantly within empirical publications in journals from various academic fields, indicating a broad, field-independent use of such systematic reviews. The selected SREL were also used as methodological orientations either for the conduct of SREL or for the practical and ethically sensitive conduct of empirical studies.

Conclusions

In our sample, SREL were rarely used to develop guidelines or to derive ethical recommendations, as it is often postulated in the theoretical literature. The findings of this study constitute a valuable preliminary empirical input in the current methodological debate on SREL and could contribute to developing strategies to align expected purposes with actual uses of SREL.
Bilirubin potentiates etomidate-induced sedation by enhancing GABA-induced currents after bile duct ligation
Authors: Gao Hao , Zhao Qian , Song Jian-Gang , Hu Guo-Xia , Yu Wei-Feng , Jiao Ying-Fu , Song Jin-Chao
Published: September 2023

Objectives

Our previous clinical trial showed that etomidate requirements to reach an appropriate level of anesthesia in patients with obstructive jaundice were reduced, which means that these patients are more sensitive to etomidate. However, the mechanism is still not completely clear. The present study was aimed to investigate the mechanism by which bilirubin facilitates etomidate induced sedation.

Methods

A bile duct ligation (BDL) rat model was used to simulate obstructive jaundice. Anesthesia sensitivity to etomidate was determined by the time to loss of righting reflex (LORR). Intrathecal injection of bilirubin was used to test the effects of bilirubin on etomidate induced sedation. The modulating effects of bilirubin on GABA responses were studied using the whole-cell patch clamp technique.

Results

The time to LORR induced by etomidate was significantly decreased in the BDL groups (p < 0.05), and unconjugated bilirubin in serum and cerebrospinal fluid (CSF) were markedly increased (p < 0.05). The time to LORR induced by etomidate was decreased after intrathecal injection of bilirubin (p < 0.05). A bilirubin concentration of 1.0 μM increased the GABA-induced currents of rat cortical pyramidal neurons (p < 0.05). Furthermore, 1.0 μM bilirubin enhanced GABA-induced currents modulated by etomidate (p < 0.05).

Conclusions

Our results demonstrated that pathologic bilirubin in CSF could enhance etomidate induced sedation. The mechanism may be that bilirubin increase the GABA-induced currents of rat pyramidal neurons.
Territorial mimetics and room types: the spatial development of Swedish district courthouses 1970–2020
Authors: Kärrholm Mattias
Published: September 2023

In this article I investigate the spatial development of Swedish district courthouses and their different room types from 1970 to 2020, with attention to the specificities and commonalities with other building types. How have spatial form and use travelled between building types during this period, and how has this contributed to the recent, quite radical developments and transformation of the courthouse as a building type? In the article, I focus particularly on aspects relating to the architectural and spatial culture of citation, and on what I call territorial mimetics here. Based on a mixed-method approach, the study traces and discusses five spatial themes of typological change in district courthouses, trends that also can be seen as a part of deeper spatial and mimetic tendencies circulating in Swedish society during these decades. I conclude with a discussion of the specific mimetic style of the courthouse as characterised by an ongoing negotiation between type-specific rules and cross-type models.