bluuebunny/crossref_metadata_2025 huggingface dataset:
451. ISOFORM SWITCHING EVENTS MAY PROVIDE NEW INSIGHT FOR THE IDENTIFICATION OF PROGNOSTIC AND THERAPEUTIC TARGETS IN ESOPHAGEAL ADENOCARCINOMA
Authors: Zhang Yun , Howard Connor , Israel Rachel , Vandenburg Bryce , Barnett Shari , Riethoven Jean-Jack , Clarke Jennifer , Lagisetty Kiran , Lin Jules , Reddy Rishindra , Chang Andrew , Kresty Laura A
Published: August 2023

Background

Esophageal adenocarcinoma (EAC) represents a growing health problem characterized by rising incidence and poor prognosis due to late-stage diagnosis coupled with treatment resistance. Although EAC is a cancer with a high mutational burden, it lacks highly prevalent oncogenic drivers that can be therapeutically targeted. Herein, we investigated whether isoform switching events, defined as a change of the dominant gene isoform, may offer prognostic or therapeutic value in EAC.

Methods

We conducted RNA-sequencing on RNA isolated from patients undergoing esophagectomy following a diagnosis of EAC or Barrett’s with high-grade dysplasia (BE.HGD). Isoform switching events between Barrett’s low-grade dysplasia (BE.LGD) and BE.HGD + EAC alone or in combination with TP53 mutation were identified using IsoformSwitchAnalyzeR. Patients were stratified into tertiles based on isoform expression level, followed by cancer-free survival analysis using the log-rank test. To evaluate whether mortality-linked isoforms influence cancer cell growth, viability, migration and response to standard chemotherapy (Paclitaxel and Carboplatin), isoform-specific siRNA knockdown experiments targeting TTLL12 and HM13 were performed in OE19 and OE33 EAC cell lines.

Results

Isoform switching events were identified in 71 genes comparing BE.LGD with BE.HGD + EAC, with 10 isoforms significantly associated with cancer-specific patient mortality. With the inclusion of TP53 mutation status, 67 genes were isoform-switched and 16 isoforms were significantly linked with cancer-specific mortality. Knockdown of TTLL12 and HM13 isoforms, two survival-linked isoforms, led to significant inhibition of cell viability and inhibition of cell migration in EAC cell lines. Moreover, combination treatment of isoform-specific siRNA and chemotherapeutic agents further decreased cell viability with synergistic effects observed in both cell lines suggesting a role for specific isoform switches in therapeutic sensitization.

Conclusions

Our research identified specific isoform switching events significantly linked to increased cancer mortality among EAC patients. Gene knockdown studies of two identified isoforms led to significant inhibition of EAC cell migration and viability with synergy observed when cells were treated with both siRNA and standard chemotherapeutic agents. In conclusion, identification of isoform switching events may provide fresh insight for the identification of prognostic markers and inform new potential therapeutic targets for EAC treatment or prevention.
453. TREATMENT AND SURVIVAL OF PATIENTS WITH A POSITIVE RESECTION MARGIN AFTER NEOADJUVANT CHEMORADIOTHERAPY AND ESOPHAGECTOMY
Authors: Zijden Charlène , Sluis Pieter , Mostert Bianca , Nuyttens Joost , Spaander Manon , Valkema Roelf , Ruurda Jelle , Wijnhoven Bas , Lagarde Sjoerd
Published: August 2023

Background

Esophagectomy after neoadjuvant chemoradiotherapy (nCRT) is associated with a tumor-positive resection margin in 4–9% of patients. Although survival in patients with a positive margin is decreased, Western guidelines do not recommend adjuvant systemic/local treatment after esophagectomy. The aim of this study was to assess whether patients underwent adjuvant therapy, regardless the lack of evidence from guidelines, and to evaluate the overall survival (OS) in patients that underwent esophagectomy and had a positive resection margin.

Methods

All patients diagnosed with resectable (cT2-4a/cTxN0–3/NxM0) esophageal or junctional cancer that underwent nCRT followed by esophagectomy between 2015 and 2021 were selected from the Netherlands’ Cancer Registry. Included were patients with a tumor-positive resection margin. The primary endpoint was the proportion of patients that started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy, radiotherapy, immunotherapy or targeted therapy. Secondary outcome OS was calculated from date of surgery until date of death or last day of follow-up, using the Kaplan Meier method.

Results

Among the 300 included patients, 98.7% had a microscopically irradical resection (R1), while 1.3% had a macroscopically irradical resection (R2). The median age was 67 (interquartile range 60–72) years and WHO 0–1 (89.3%). Esophagectomy was performed open (8.3%), laparoscopically (57.7%) or robot-assisted (33%) and via transthoracic (89.7%) or transhiatal approach (8.7%). Some 71% of tumors had a partial response (Mandard category 1–3) or no pathological response (Mandard 4–5; 12.7%) to nCRT. One patient underwent external radiotherapy after esophagectomy. Twenty patients (7%) underwent adjuvant immunotherapy (nivolumab), despite their irradical resection. Median OS of all patients was 18.6 months (95% CI 14.7–22.4).

Conclusion

Real-world population level data showed that 7% of patients were treated with adjuvant immunotherapy, despite lack of evidence of the benefit thereof in patients with an irradical resection. This underlines the need for better neoadjuvant therapy leading to less irradical resections, as well as prospective studies evaluating adjuvant therapy in patients with an irradical resection.
456. PHYSICAL ACTIVITY AND FRAILTY AS PART OF HEALTH RELATED QUALITY OF LIFE ASSESSMENT IN ESOPHAGEAL CANCER SURVIVORS AFTER CURATIVE ESOPHAGECTOMY
Authors: Boyle Ellen , Elliott Jessie , Greene Christine , Murphy Conor , Donlon Noel , Donohoe Claire , Ravi Narayasamy , Reynolds John
Published: August 2023

Background

Survival rates for patients with esophageal cancer are improving, resulting in an increasing population of esophageal cancer survivors. Surgery is the mainstay of treatment but has a high risk of post-operative morbidity. This study aimed to characterise health related quality of life with a specific focus on physical activity and frailty assessment within an esophageal cancer survivor population.

Methods

This was a cross-sectional cohort study of patients who underwent esophageal cancer surgery between 2010 and 2015. A multicomponent questionnaire was distributed to disease-free patients at least one year post completion of treatment. Linear and logistic regression analyses were utilised to determine the impact of treatment and pathologic variables on physical activity and frailty.

Results

On multivariable analysis, age was a significant predictor of level of physical activity (P = 0.001). Male sex, critical care length of stay and eating symptoms were independent predictors of frailty in both the PRISMA7 and SARCF tools (all P < 0.001). Inpatient length of stay (P < 0.001) and persistent eating symptoms following treatment (P < 0.001) were both predictive of physical function following completion of treatment.

Conclusion

Curative esophagectomy can have significant effects on patients physical function, levels of physical activity and risk of frailty. Current methods of assessing health related quality of life in esophageal cancer survivorship may under-investigate the effects of curative esophagectomy on physical activity and frailty. Further research is warranted to investigate how patient pathways can be enhanced to minimise the long-term health-related quality of life impact of curative treatment.
460. INTRAEPITHELIAL EOSINOPHILS IN ACHALASIA PATIENTS ARE NOT UNCOMMON, BUT THEY SEEM NOT RELATED TO THE COURSE OF THE DISEASE
Authors: Costantini Andrea , Forattini Francesca , Ghisa Matteo , Angerilli Valentina , Provenzano Luca , Capovilla Giovanni , Vittori Arianna , Nezi Giulia , Costantini Mario , Valmasoni Michele , Fassan Matteo , Savarino Edoardo , Salvador Renato
Published: August 2023

Background

The presence of intraepithelial eosinophils (IE) was described in patients with esophageal motor disorders (EMD). Conversely, EMD and even achalasia were reported in patients with eosinophilic esophagitis (EoE). The purpose of this study was to further investigate this possible association.

Methods

From February to July 2022, patients with achalasia undergoing laparoscopic myotomy were evaluated. Patients who had previous treatment were excluded. Immediately before the operation, the patients underwent endoscopy with the addition of 4 biopsies from the proximal, middle and distal esophagus and from the Z line, respectively. Two additional samplings of the esophageal muscle were taken while performing the myotomy. The specimens were stained with H&E in order to highlight the presence of eosinophils and the number of IE eventually present in a high-power field (hpf) was recorded. Patients were re-evaluated 6 months after the operation.

Results

A total of 30 patients with a median age of 45.5 years were studied. Their preoperative ES was 6 (5–7) and the median duration of symptoms was 42 months (12–120); there were 18 stage I, 9 stage II, 2 stage III and only one stage IV, respectively; manometric subtype 1 was found in 7 patients, subtype 2 in 18 and subtype 3 in 5. There were no complications. All the patients had a good outcome and the median ES was 0 (0–1). IE were found in 6 patients (20%) [median 6/hpf (2–10)]. Only one patient met the pathologic criteria for EoE, whereas only one additional showed eosinophils in the muscular specimen. No differences in preoperative and postoperative data were found between patients with and without IE, but the maximum diameter of the gullet was narrower in the former than in the latter (3.24 cm vs 22.50 cm, respectively, p < 0.05).

Conclusions

EoE and achalasia are 2 of the commonest causes of dysphagia and an association between them was recently hypothesized. Our study confirmed that IE are present in some patients with achalasia, but seldom meeting the criteria for EoE. Only a narrower esophagus was found in patients with IE as compared to those without, possibly reflecting an earlier stage of the disease.
478. ROBOTIC REPAIR OF EPIPHRENIC DIVERTICULUM
Authors: Bianchi Edno Tales , Szachnowicz Sergio , Cirlinas Alexandra , Sallum Rubens
Published: August 2023

We show a robotic repair of a epiphrenic diverticulum in a patient with a previous treatment 10 years ago by laparoscopic with diverticulectomy with a heller miotomy. This time we performed a complete ressection with a new miotomy in a thoracic aproach https://drive.google.com/file/d/1ancYQoy9csA1NjXhswGuDtkd1EjR0M7B/view?usp = sharing.
483. INTRAOPERATIVE EVALUATION OF HIATAL HERNIA SIZE AND CANDIDACY IN TIF ELIGIBLE PATIENTS
Authors: Harrison Madison , Stiles Erik , Hubka Michal
Published: August 2023

Background

Transoral incisionless fundoplication (TIF) is gaining prominence in treatment of gastroesophageal reflux disease (GERD) for patients with absent or small hiatal hernia. As TIF gains popularity, appropriate patient evaluation and selection is paramount in establishing anatomical candidacy hence successful outcome. We evaluated patients who were intended to be treated with TIF and underwent a standard evaluation but instead underwent robotic hiatal hernia repair. We compared their preoperative evaluation of hernia size with intraoperative findings.

Methods

A cohort of seventy-six patients from a single-center database from January 2020 to March 2023 were retrospectively analyzed. All were deemed candidates for TIF based on our inclusion criteria (pH confirmation of GERD, hiatal hernia <2 cm) and underwent preoperative testing with endoscopy, esophagram, pH and manometry. Twenty-seven of these patients either were denied TIF by their insurance company or had personal preference for surgery (daVHH) over endoscopic intervention and underwent robotic assisted paraesophageal hernia repair. We examined intraoperative measurements of hiatal hernia size and EG junction anatomy and compared them to standard preoperative evaluation.

Results

On pre-operative endoscopy 23 patients were found to have no hiatal hernia, 20 were found to have a small hernia, 3 a medium hernia, and 1 a large hernia. Esophagram evaluation demonstrated no hiatal hernia in 17 patients and a small hernia in 23 patients. The average hiatal hernia size seen during manometry was 0.54 cm (0–2 cm) while the average hernia seen intra-operatively was 3.26 cm (1.5–4.8 cm). There was a significant difference between preoperative hernia size evaluated by manometry and intraoperative hernia size (p-value 0.04).

Conclusion

Standard preoperative evaluation of patients intended to be treated with TIF appears to have a tendency to underestimate the size of hiatal hernia and omits evaluation of paraesophageal anatomy. This can lead to poor patient selection of failure of this treatment modality. Addition of cross-sectional imaging to the evaluation of patients with small hiatal hernias can facilitate a more meaningful therapeutic decision making for endoscopic, surgical, and combination treatment options.
490. SIGNIFICANCE OF NUTRITIONAL EVALUATION USING GLIM CRITERIA IN PATIENTS WITH ESOPHAGEAL CANCER
Authors: Ogata Takashi , Kanematsu Kyohei , Tanabe Mie , Onuma Shizune , Morita Junya , Nagasawa Shinsuke , Yamada Takanobu , Oshima Takashi
Published: August 2023

Background

Patients with advanced esophageal cancer may have dysphagia and weight loss from the first visit, and it is necessary to evaluate their nutritional status before starting treatment, especially for preoperative patients. On the other hand, since 2018, the global diagnostic criteria for malnutrition, the GLIM criteria, have been proposed to define malnutrition and its severity.

Purpose

The aim of the study is to examine the impact of malnutrition severity assessment using the GLIM criteria at the time of first visit in patients with advanced esophageal cancer on short-term prognosis (length of hospital stay after surgery) and long-term prognosis (presence or absence of recurrence, OS) in patients undergoing surgery for esophageal cancer.

Method

From 2011 to 2018, 197 advanced esophageal cancer patients have undergone esophagectomy, and we examined the distribution of malnutrition at the first visit of these patients. Based on the GLIM criteria, low BMI in Asians (<18.5: less than 70 years old, <20: over 70 years old) is defined as malnutrition, and moderate malnutrition and severe malnutrition are defined according to the weight loss rate.

Result

42 patients (21.3%) were judged to be malnourished according to the GLIM criteria at the first visit. 23 patients were judged moderately malnourished, and 19 patients were judged severely malnourished. There was no significant difference in postoperative length of hospital stay between the normal nutrition group and the malnutrition group, regardless of the severity of the disease. There was no significant difference in recurrence, but the severely undernourished group had a significantly high rate of recurrences (p < 0.01). Regarding prognosis, the 3-year survival rate tended to be slightly lower in the malnutrition group (p = 0.081), but the 3-year survival rate was significantly lower in the severely malnutrition group (p < 0.001).

Conclusion

In patients with advanced esophageal cancer, the severe malnutrition group in the GLIM criteria at the time of the first visit was considered to have a poor long-term prognosis, although the short-term prognosis was similar to that of the eutrophic group. Currently, in Japan, NAC is usually performed for operable advanced esophageal cancer, so in the future, we plan to focus on improving the nutritional status from the beginning of NAC to surgery.
The Ga1 locus of the genus Zea is associated with novel genome structures derived from multiple, independent nonhomologous recombination events
Authors: Bapat Amruta R , Moran Lauter Adrienne N , Hufford Matthew B , Boerman Nicholas A , Scott M Paul
Published: August 2023

The Ga1 locus controls cross-incompatibility between field corn and popcorn. The Ga1-S haplotype contains 2 types of pectin methylesterase (PME) genes, ZmPme3 and several copies of ZmGa1P that are expressed in silk and pollen, respectively. The ga1 haplotype contains nonfunctional tandem repeat sequences related to ZmPme3 and ZmGa1P. This haplotype can cross-pollinate freely and is widely present in field corn. The primary objective of this study is to characterize the repeat sequences from a diverse collection of maize and teosinte lines and use this information to understand the evolution of the Ga1 locus. First, we characterized the complexity of the Ga1 genome region in high-quality maize genome assemblies that led to their categorization into 5 groups based on the number and type of PME-like sequences found at this region. Second, we studied duplication events that led to the ga1 and Ga1-S repeats using maximum likelihood phylogenetic reconstruction. Divergence estimates of the ga1 haplotype suggest that the duplication events occurred more than 600 KYA whereas those in Ga1-S occurred at 3 time points, i.e. >600, ∼260, and ∼100 KYA. These estimates suggest that the ga1 and Ga1-S tandem duplication events occurred independently. Finally, analysis of ZmPme3 and ZmGa1P homologs in Zea and Tripsacum genomes suggests that ga1 and Ga1-S repeats originated from an ancestral pair of PME genes that duplicated and diverged through 2 evolutionary branches prior to the domestication of maize.
“We’re Not Patients. We’re Inmates”: Older Black Women’s Experience of Aging, Health, and Illness During and After Incarceration
Authors: James Jennifer Elyse
Published: August 2023

Background and Objectives

The incarcerated population is growing older and by the year 2030, more than one third of people incarcerated in the United States will be over the age of 55. This population shift will have a profound impact on correctional health care systems as older incarcerated people often have multiple chronic illnesses and correctional institutions were not designed with aging and disability in mind. Black women experience greater burdens of comorbid conditions and are disproportionately represented among incarcerated women.

Research Design and Methods

We utilized Black Feminist Epistemological Methodology to explore the intersection of aging, chronic illness, and mass incarceration via in-depth interviews with 13 formerly incarcerated older Black women.

Results

First, participants described needing to prove themselves to be trustworthy prior to becoming ill in order to be believed and granted access to care when they report symptoms. Next, participants report being treated, not as patients, but as “inmates.” The punitive nature of prison health care disrupted the patient–provider relationship and complicated the ability of patients to maintain autonomy in health care interactions. Finally, I describe how carceral health extends beyond the walls of both the clinic and the institution.

Discussion and Implications

For older Black women, medical care and decision making inside prisons occur within a punitive context, which presents unique barriers when seeking care. Their experiences of health and illness while incarcerated may continue to influence if and how they seek care as they age in the community and thus must be interrogated when discussing aging in the Black community.
3. Market Power, Market Definition, and Barriers to Entry
Authors: Jones Alison , Sufrin Brenda , Dunne Niamh
Published: August 2023

Market power is a central concept in EU competition law. This chapter considers what is meant by market power and how it is assessed in EU law using market definition and barriers to entry analysis. It discusses how markets are defined in EU law by looking at demand substitution, supply substitution, and potential competition. It explains that markets may have both a product and a geographic dimension. The chapter examines the draft new Commission Notice on the definition of the relevant market to replace the 1997 Notice, the decisional practice of the Commission, and the case law of the EU Courts on market definition, and it discusses what tests may be employed in the definition of markets, particularly the SSNIP test. The chapter then considers how the power of a firm on a market is affected by barriers to entry. It discusses the definition of a barrier to entry and considers barriers to entry such as sunk costs, structural barriers, and strategic barriers,
7. Article 102 TFEU: Conduct Which Can be an Abuse
Authors: Jones Alison , Sufrin Brenda , Dunne Niamh
Published: August 2023

This chapter discusses the difficult concept of what constitutes an ‘abuse’ of a dominant position for the purposes of Article 102. It considers the case law of the EU Courts, the decisional practice of the Commission, and the Commission’s Guidance Paper on enforcement priorities, and the problem of distinguishing competition on the merits from illegitimate conduct. The chapter looks at the different classifications of abuse, particularly exclusionary and exploitative abuses; the distinction between form- and effects-based approaches to types of abuse; the leveraging of market power between distinct markets as a theory of harm; the objective justification defence; and general issues in respect of abuses concerning prices, including the ‘as efficient competitor’ test. The chapter then examines the application of Article 102 to various forms of conduct, including: price discrimination; predatory pricing; selective low pricing; margin squeeze; exclusive dealing; tying and bundling; refusal to supply; self-preferencing; malicious pursuit of legal proceedings; ‘regulatory gaming’; discrimination abuses; unfairly high and low pricing; and hindering inter-Member State trade.
8. Competition and the State: Article 106 TFEU
Authors: Jones Alison , Sufrin Brenda , Dunne Niamh
Published: August 2023

This chapter examines how competition law applies to the actions of the State when it intervenes in the market through undertakings which it controls or owns or which it places in a privileged position. The discussion includes the principle of Union loyalty in Article 4(3) TEU; Article 106(1); Article 106(2); and the Commission’s supervisory and policing powers in Article 106(3). Article 106(1) is a prohibition addressed to Member States against enacting or maintaining in force any measure in relation to public undertakings or undertakings to which they have granted special or exclusive rights which are contrary to the Treaty rules. The chapter discusses what is meant by ‘public undertakings’ and ‘special or exclusive rights’ and examines in the light of the case law what measures are forbidden by Article 106(1), including those involving the cumulation of rights, the extension of a dominant position from one market to another, and the creation of situations of inequality of opportunity. Article 106(2) gives a limited derogation from Article 106(2) to undertakings entrusted with the operation of services of general economic interest (SGEIs). The chapter discusses the concept of ‘services of general economic interest’ and examines the cases in which the derogation has been applied or not applied, including the application of Article 106(2) to compensation for the provision of SGEIs which constitutes State aid. The chapter also considers Article 106(3) and the question of the direct effect of Article 106(1) and (2).
12. Licensing Agreements and Other Agreements Involving Intellectual Property Rights
Authors: Jones Alison , Sufrin Brenda , Dunne Niamh
Published: August 2023

This chapter examines some of the different types of intellectual property rights (IPRs) before outlining the relationship between intellectual property and both EU competition law and the EU free movement rules. It focuses, however, on IP licensing agreements and their treatment under Article 101. The chapter traces the development of EU competition policy to IP licensing agreements and examine the current Technology Transfer Block Exemption and the Guidelines in detail. It also examines patent settlement agreements (including pay for delay agreements), patent pools, trademark licences, trademark delimitation agreements, and copyright (other than software) licences not covered by the TTBER and Guidelines.
13. Public Enforcement of Article 101 and Article 102 by the Commission and the National Competition Authorities
Authors: Jones Alison , Sufrin Brenda , Dunne Niamh
Published: August 2023

This chapter discusses the public enforcement regime for the application of Articles 101 and 102 under Regulation 1/2003. The chapter examines: the complaints procedure; the powers of the Commission, including the investigation and inter partes stages of its procedure; the decisions which the Commission may take, including decisions imposing fines and commitments decisions; judicial review by the EU Courts; the European Competition Network (ECN) and enforcement by national competition authorities, including the requirements of the ECN+ Directive; and the possibility of sanctions against individuals. The chapter also considers the application of fundamental rights provisions in EU competition proceedings.
15. Mergers
Authors: Jones Alison , Sufrin Brenda , Dunne Niamh
Published: August 2023

This chapter discusses the regime for controlling mergers which have an ‘EU dimension’ under the European Union Merger Regulation (EUMR). The chapter examines: the purposes of merger control; the history of the EUMR; the scheme of the EUMR and the concept of the ‘one-stop shop’; jurisdiction under the EUMR, including the definition of a ‘concentration’ and what amounts to an ‘EU dimension’; procedure, including Phase I and Phase II proceedings; the substantive appraisal of horizontal, and non-horizontal, mergers under the EUMR and the test of significantly impeding effective competition (SIEC); EUMR statistics; appeals; and international issues. It considers current controversial issues, including whether merger control is sufficiently rigorous, how acquisitions of start-ups or impacting on innovation should be assessed, whether a new substantive test for appraisal of mergers is required, and whether, and if so when, public interest (or non-competition) factors, such as the impact of a concentration on jobs, equality, sustainability, democracy, industrial policy, or national security, should affect the appraisal of a merger.
Harris, O'Boyle, and Warbrick: Law of the European Convention on Human Rights
Authors: Harris David , O'Boyle Michael , Bates Ed , Buckley Carla M.
Published: August 2023

This fifth edition of Law of the European Convention on Human Rights builds on the great strengths of earlier editions. An up-to-date account of Strasbourg case law and its underlying principles, this title facilitates an understanding of this key area of law. It explores the extent of the Convention’s influence upon the legal development of the contracting states, and reveals exactly how such a considerable impact has been achieved and maintained. It sets out and critically analyses the Strasbourg jurisprudence on each Convention Article that constitutes the substantive guarantee, and examines the system of supervision. The Convention is firmly established in Europe’s constitutional landscape, providing common human rights standards for the continent. National parliaments and courts must constantly look to the Convention when legislating and deciding cases, or run the risk of adverse Strasbourg judgments with which they must then comply. For all states, the Convention has been made enforceable in their national courts. The fifth edition takes account of Strasbourg jurisprudence responding to new human rights crises in Europe resulting from the erosion of the rule of law in some states, the Covid pandemic and recent inter-state armed conflict.
Understanding communication in community engagement for maternal and newborn health programmes in low- and middle-income countries: a realist review
Authors: Dada Sara , Aivalli Praveenkumar , De Brún Aoife , Barreix Maria , Chelwa Nachela , Mutunga Zaccheous , Vwalika Bellington , Gilmore Brynne
Published: August 2023

As community engagement (CE) is implemented for sustainable maternal and newborn health (MNH) programming, it is important to determine how these approaches work. Low- and middle-income countries (LMICs) have become a particular focus for MNH CE activities due to their high burden of maternal and neonatal deaths. MNH messaging and communication to engage communities are likely to differ by context, but how these approaches are actually developed and implemented within CE is not well understood. Understanding how communications in CE actually work is vital in the translation of learnings across programmes and to inform future projects. The purpose of this realist review is to describe how, why, to what extent and for whom communications in CE contribute to MNH programming in LMICs. After searching academic databases, grey literature and literature suggested by the expert advisory committee, documents were included if they described the CE communication processes/activities used for MNH programming in an LMIC. Relevant documents were assessed for richness (depth of insight) and rigor (trustworthiness and coherence of data/theories). Data were extracted as context–mechanism–outcome configurations (CMOCs) and synthesized into demi-regularities to contribute to theory refinement. After screening 416 records, 45 CMOCs were extracted from 11 documents. This informed five programme theories explaining that communications in CE for an MNH programme work when: communities are actively involved throughout the programme, the messaging and programme are acceptable, communication sources are trusted, the community has a reciprocal relationship with the programme and the community sees value in the programme. While these findings reflect what is often anecdotally known in CE or acknowledged in communications theory, they have implications for policy, practice and research by highlighting the importance of centring the community’s needs and priorities throughout the stages of developing and implementing communications for CE in MNH.
Relationship Between Rectal Swab and Tissue Samples in Mucosa-associated Microbiota in Patients With Inflammatory Bowel Disease
Authors: Liu Tsunglin , Lin Cheng-Han , Chen Yi-Lin , Yeh Chien-Cheng , Chiou Yuan-Yow , Wang Jiu-Yao , Lee Chung-Ta , Lee Kuo-Ting , Shiau Ai-Li , Wu Chao-Liang , Chen Chien-Chin , Kang Jui-Wen , Chen Po-Jun , Kuo Hsin-Yu , Yang Er-Hsiang , Chuang Chiao-Hsiung
Published: August 2023

Background

Gut mucosa-associated microbiota is more closely correlated with disease phenotypes than fecal microbiota; however sampling via tissue biopsy is more invasive and uncomfortable. Rectal swab may be a suitable substitute for tissue biopsy, but its effectiveness is controversial. This study aimed to evaluate differences in the microbiota at these sites in patients with inflammatory bowel disease (IBD).

Methods

Inflammatory bowel disease patients and a control group were enrolled when surveillance colonoscopy was scheduled. Samples of colon biopsy tissues, rectal swabs during colonoscopy, and feces before bowel preparation were collected to analyze microbial composition. To explore the short-term effects of bowel preparation on swab microbiota, prepreparation swab samples were also collected from 27 IBD patients.

Results

A total of 33 Crohn’s disease, 54 ulcerative colitis, and 21 non-IBD patients were enrolled. In beta diversity analysis, fecal microbiota clearly differed from swab and tissue microbiota in the 3 disease groups. The swab microbiota was closer to, but still different from, the tissue microbiota. Consistently, we identified that swab samples differed more in abundant genera from feces than from tissue. Beta diversity analysis did not reveal a difference in swab microbiota before and after bowel preparation, but the genus composition of most individuals varied markedly.

Conclusions

Swab microbiota more closely resembled tissue microbiota relative to fecal microbiota, but there were still differences. Bowel preparation did not alter the overall swab microbiota in the short term but markedly changed the microbial composition in most patients.
Pooling Different Placebos as a Control Group in a Randomized Platform Trial: Benefits and Challenges From Experience in the ACTIV-2 COVID-19 Trial
Authors: Moser Carlee B , Chew Kara W , Ritz Justin , Newell Matthew , Javan Arzhang Cyrus , Eron Joseph J , Daar Eric S , Wohl David A , Currier Judith S , Smith Davey M , Hughes Michael D ,   for the ACTIV-2/A5401 Study Team, Hosey Lara , Roa Jhoanna , Patel Nilam , Aldrovandi Grace , Murtaugh William , Cooper Marlene , Gutzman Howard , Knowles Kevin , Bowman Rachel , Giganti Mark , Erhardt Bill , Adams Stacey
Published: August 2023

Adaptive platform trials were implemented during the coronavirus disease 2019 (COVID-19) pandemic to rapidly evaluate therapeutics, including the placebo-controlled phase 2/3 ACTIV-2 trial, which studied 7 investigational agents with diverse routes of administration. For each agent, safety and efficacy outcomes were compared to a pooled placebo control group, which included participants who received a placebo for that agent or for other agents in concurrent evaluation. A 2-step randomization framework was implemented to facilitate this. Over the study duration, the pooled placebo design achieved a reduction in sample size of 6% versus a trial involving distinct placebo control groups for evaluating each agent. However, a 26% reduction was achieved during the period when multiple agents were in parallel phase 2 evaluation. We discuss some of the complexities implementing the pooled placebo design versus a design involving nonoverlapping control groups, with the aim of informing the design of future platform trials.

Clinical Trials Registration. NCT04518410.
Variant-Specific Viral Kinetics in Acute COVID-19
Authors: Ribeiro Ruy M , Choudhary Manish C , Deo Rinki , Giganti Mark J , Moser Carlee , Ritz Justin , Greninger Alexander L , Regan James , Flynn James P , Wohl David A , Currier Judith S , Eron Joseph J , Hughes Michael D , Smith Davey M , Chew Kara W , Daar Eric S , Perelson Alan S , Li Jonathan Z ,   for the ACTIV-2/A5401 Study Team, Hosey Lara , Roa Jhoanna , Patel Nilam , Aldrovandi Grace , Murtaugh William , Science Frontier , Cooper Marlene , Gutzman Howard , Knowles Kevin , Bowman Rachel , Erhardt Bill , Adams Stacey
Published: August 2023

Understanding variant-specific differences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics may explain differences in transmission efficiency and provide insights on pathogenesis and prevention. We evaluated SARS-CoV-2 kinetics from nasal swabs across multiple variants (Alpha, Delta, Epsilon, Gamma) in placebo recipients of the ACTIV-2/A5401 trial. Delta variant infection led to the highest maximum viral load and shortest time from symptom onset to viral load peak. There were no significant differences in time to viral clearance across the variants. Viral decline was biphasic with first- and second-phase decays having half-lives of 11 hours and 2.5 days, respectively, with differences among variants, especially in the second phase. These results suggest that while variant-specific differences in viral kinetics exist, post–peak viral load all variants appeared to be efficiently cleared by the host.

Clinical Trials Registration. NCT04518410.
Dichotomous roles of RIPK3 in regulating the IFN response and NLRP3 inflammasome in human monocytes
Authors: Yang Chao , Yuan Ruoxi , Brauner Caroline , Du Yong , Ah Kioon Marie Dominique , Barrat Franck J , Ivashkiv Lionel B
Published: August 2023

Regulation of the profile and magnitude of toll-like receptor (TLR) responses is important for effective host defense against infections while minimizing inflammatory toxicity. The chemokine CXCL4 regulates the TLR8 response to amplify inflammatory gene and inflammasome activation while attenuating the interferon (IFN) response in primary monocytes. In this study, we describe an unexpected role for the kinase RIPK3 in suppressing the CXCL4 + TLR8–induced IFN response and providing signal 2 to activate the NLRP3 inflammasome and interleukin (IL)-1 production in primary human monocytes. RIPK3 also amplifies induction of inflammatory genes such as TNF, IL6, and IL1B while suppressing IL12B. Mechanistically, RIPK3 inhibits STAT1 activation and activates PI3K-Akt–dependent and XBP1- and NRF2-mediated stress responses to regulate downstream genes in a dichotomous manner. These findings identify new functions for RIPK3 in modulating TLR responses and provide potential mechanisms by which RIPK3 plays roles in inflammatory diseases and suggest targeting RIPK3 and XBP1- and NRF2-mediated stress responses as therapeutic strategies to suppress inflammation while preserving the IFN response for host defense.
Mitochondria-induced formation of neutrophil extracellular traps is enhanced in the elderly via Toll-like receptor 9
Authors: Pastorek Michal , Konečná Barbora , Janko Jakub , Janovičová Ľubica , Podracká Ľudmila , Záhumenský Jozef , Šteňová Emöke , Dúbrava Martin , Hodosy Július , Vlková Barbora , Celec Peter
Published: August 2023

Neutrophil extracellular traps are potent antimicrobial weapons; however, their formation during sterile inflammation is detrimental, and the mechanism of induction is still unclear. Since advanced age is the primary clinical risk factor for poor outcomes in inflammatory diseases, we hypothesized that sterile stimuli, represented by mitochondria, would induce neutrophil extracellular trap formation in an age-dependent manner. Therefore, we analyzed induction of neutrophil extracellular traps in patients grouped according to age or immune status and observed that neutrophils from elderly patients responded to the presence of mitochondria with enhanced neutrophil extracellular trap formation. These neutrophil extracellular traps were also found to be more oxidized and exhibited higher resistance to DNase I degradation. Additionally, a higher concentration of residual neutrophil extracellular traps was detected in the plasma of the elderly. This plasma was capable of priming neutrophils through TLR9-mediated signaling, leading to further neutrophil extracellular trap formation, which was successfully inhibited with chloroquine. Finally, in a mouse model of mitochondria-induced acute lung injury, we observed that neutrophils from aged mice displayed impaired chemotactic activity but exhibited a trend of higher neutrophil extracellular trap formation. Thus, we propose that residual neutrophil extracellular traps circulating in the elderly preactivate neutrophils, making them more prone to enhanced neutrophil extracellular trap formation when exposed to mitochondria during sterile inflammation. Further investigation is needed to determine whether this vicious circle could be a suitable therapeutic target.
The potential invasion into North America and Europe by non-native mosquito, Aedes koreicus (Diptera: Culicidae)
Authors: Seok Sangwoo , Kim Zhonghyun , Nguyen Valerie T , Lee Yoosook
Published: August 2023

Aedes koreicus (Edward, 1917) (Diptera: Culicidae), a mosquito species native to East Asia, has spread to parts of Europe and Central Asia since 2008. The species shares ecological characteristics with Aedes japonicus (Theobald, 1901) (Diptera: Culicidae), which has already successfully invaded and established in North America and Europe. Given these similarities, it is plausible that Ae. koreicus may also invade North America in the future. However, the invasion of Ae. koreicus may be masked or have delayed detection due to their similar morphologies with Ae. japonicus. This study highlights the potential risks of invasion of Ae. koreicus into North America, especially in the northeastern United States, and for further expansion in Europe. We used the maximum entropy model to identify areas with a high likelihood of presence in North America and Europe using comprehensive occurrence records from East Asia, Central Asia, and Europe. We have identified 15 additional countries in Europe and 7 states in the United States that will likely have suitable environments for Ae. koreicus. Additionally, we reviewed the morphological characteristics of Ae. koreicus and Ae. japonicus and provided morphological keys to distinguish the 2 species. Morphological results contradicting previous studies suggested that finding the origin by morphological comparison between Ae. koreicus populations may need re-evaluation. The information presented here will be useful for researchers and public health professionals in high-risk areas to be informed about morphological characteristics to distinguish Ae. koreicus from similar-looking Ae. japonicus. These tools will allow more careful monitoring of the potential introduction of this highly invasive species.
Undocumented Bordering Practices: Protagonism and Spaces of Making
Authors: Biorklund Linn
Published: August 2023

Borders are at the centre of everyday lives, often with gendered and violent outcomes exacerbating harm across space and time. The feminization of waiting is embedded in the power structures of borders. Yet, feminized waiting in the context of displacement can also be a necessary pre-condition for generating affective geographies of making, and transformative spaces of solidarity and contestation across borders. This paper draws on ethnographic and feminist participatory action research carried out in southern Mexico to document bordering practices ‘from below’, Undocumented Bordering Practices performed by women from Central America experiencing waiting in the Mexico–Guatemala borderlands. I expand the definitions of bordering and refugee protection by centring on women’s protagonism (self-authorship) and collective acts of making (art, food, and spaces of care) as they wait. I illustrate three processes of making while waiting: The making of a ‘mural-on-the-move’, a newsletter titled Breaking Barriers: When women migrate, life migrates, and intimate geopolitics of making and sharing food in borderlands.
Characterizing Two New Henneguya Species in the Respiratory Organs of African Sharptooth Catfish
Authors: Emeish Walaa F A , Fawaz Marwa M , Hussein Nermean M , Al-Amgad Zeinab , Abd-ElHafeez Hanan H , Rutland Catrin Sian , Bakry Karima A
Published: August 2023

Henneguya species are myxozoans, a suborder of Cnidaria, which can affect the gills and extrarespiratory organs of the African sharptooth catfish, Clarias gariepinus. This research describes natural infection-induced histological alterations caused by the Henneguya species present. The Henneguya species were also identified molecularly using DNA sequenced from infected tissue cysts, and phylogenetically analyzed. Clinical investigations revealed cyst-like nodules on the fish gill filaments and extrarespiratory organs. Within a milky fluid inside the cysts were several Henneguya-like spores. Henneguya sp. infested 27.5% of the fish, with the highest prevalence in the gills compared to the extrarespiratory organs. The Henneguya species parasitized the gill and the dendritic tissues, resulting in histopathological characteristics. The plasmodia's developmental stages resulted in destructive damage which manifested as marked necrosis, which was replaced by a focal aggregation of inflammatory cells. Amplification of the 18S ribosomal DNA from the fish parasites was followed by sequencing, which confirmed their identities as new species Henneguya qenabranchiae n. sp. and Henneguya qenasuprabranchiae n. sp. with 99.53 and 99.64% identities, respectively, to Henneguya sp. 1 HS-2015. The two C. gariepinus myxozoans shared some characteristics based on morphologic and phylogenetic analysis as previously published, where it was proposed that they were a sister lineage to Henneguya species in Egypt, and it is now proposed that they are new species.
Asteroseismology of δ Scuti stars: emulating model grids using a neural network
Authors: Scutt Owen J , Murphy Simon J , Nielsen Martin B , Davies Guy R , Bedding Timothy R , Lyttle Alexander J
Published: August 2023

Young δ Scuti (Sct) stars have proven to be valuable asteroseismic targets, but obtaining robust uncertainties on their inferred properties is challenging. We aim to quantify the random uncertainties in grid-based modelling of δ Sct stars. We apply Bayesian inference using nested sampling and a neural network emulator of stellar models, testing our method on both simulated and real stars. Based on results from simulated stars, we demonstrate that our method can recover plausible posterior probability density estimates while accounting for both the random uncertainty from the observations and neural network emulation. We find that the posterior distributions of the fundamental parameters can be significantly non-Gaussian and multimodal, and have strong covariance. We conclude that our method reliably estimates the random uncertainty in the modelling of δ Sct stars and paves the way for the investigation and quantification of the systematic uncertainty.
Updated Phylogeny and Protein Structure Predictions Revise the Hypothesis on the Origin of MADS-box Transcription Factors in Land Plants
Authors: Qiu Yichun , Li Zhen , Walther Dirk , Köhler Claudia
Published: August 2023

MADS-box transcription factors (TFs), among the first TFs extensively studied, exhibit a wide distribution across eukaryotes and play diverse functional roles. Varying by domain architecture, MADS-box TFs in land plants are categorized into Type I (M-type) and Type II (MIKC-type). Type I and II genes have been considered orthologous to the SRF and MEF2 genes in animals, respectively, presumably originating from a duplication before the divergence of eukaryotes. Here, we exploited the increasing availability of eukaryotic MADS-box sequences and reassessed their evolution. While supporting the ancient duplication giving rise to SRF- and MEF2-types, we found that Type I and II genes originated from the MEF2-type genes through another duplication in the most recent common ancestor (MRCA) of land plants. Protein structures predicted by AlphaFold2 and OmegaFold support our phylogenetic analyses, with plant Type I and II TFs resembling the MEF2-type structure, rather than SRFs. We hypothesize that the ancestral SRF-type TFs were lost in the MRCA of Archaeplastida (the kingdom Plantae sensu lato). The retained MEF2-type TFs acquired a Keratin-like domain and became MIKC-type before the divergence of Streptophyta. Subsequently in the MRCA of land plants, M-type TFs evolved from a duplicated MIKC-type precursor through loss of the Keratin-like domain, leading to the Type I clade. Both Type I and II TFs expanded and functionally differentiated in concert with the increasing complexity of land plant body architecture. The recruitment of these originally stress-responsive TFs into developmental programs, including those underlying reproduction, may have facilitated the adaptation to the terrestrial environment.