bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic zinc fluxes regulate meiotic progression in Caenorhabditis elegans
Authors: Mendoza Adelita D , Sue Aaron , Antipova Olga , Vogt Stefan , Woodruff Teresa K , Wignall Sarah M , O’Halloran Thomas V 
Published: April 2022

Abstract
Zinc influx and efflux events are essential for meiotic progression in oocytes of several mammalian and amphibian species, but it is less clear whether this evolutionary conservation of zinc signals is also important in late-stage germline development in invertebrates. Using quantitative, single cell elemental mapping methods, we find that Caenorhabditis elegans oocytes undergo significant stage-dependent fluctuations in total zinc content, rising by over sevenfold from Prophase I through the beginning of mitotic divisions in the embryo. Live imaging of the rapid cell cycle progression in C. elegans enables us to follow changes in labile zinc pools across meiosis and mitosis in single embryo. We find a dynamic increase in labile zinc prior to fertilization that then decreases from Anaphase II through pronuclear fusion and relocalizes to the eggshell. Disruption of these zinc fluxes blocks extrusion of the second polar body, leading to a range of mitotic defects. We conclude that spatial temporal zinc fluxes are necessary for meiotic progression in C. elegans and are a conserved feature of germ cell development in a broad cross section of metazoa.
Assessing executive functions in post-stroke aphasia—utility of verbally based tests
Authors: Schumacher Rahel , Halai Ajay D. , Lambon Ralph Matthew A. 
Published: April 2022

Abstract
It is increasingly acknowledged that, often, patients with post-stroke aphasia not only have language impairments but also deficits in other cognitive domains (e.g. executive functions) that influence recovery and response to therapy. Many assessments of executive functions are verbally based and therefore usually not administered in this patient group. However, the performance of patients with aphasia in such tests might provide valuable insights both from a theoretical and clinical perspective. We aimed to elucidate (i) if verbal executive tests measure anything beyond the language impairment in patients with chronic post-stroke aphasia, (ii) how performance in such tests relates to performance in language tests and nonverbal cognitive functions, and (iii) the neural correlates associated with performance in verbal executive tests. In this observational study, three commonly used verbal executive tests were administered to a sample of patients with varying aphasia severity. Their performance in these tests was explored by means of principal component analyses, and the relationships with a broad range of background tests regarding their language and nonverbal cognitive functions were elucidated with correlation analyses. Furthermore, lesion analyses were performed to explore brain–behaviour relationships. In a sample of 32 participants, we found that: (i) a substantial number of patients with aphasia were able to perform the verbal executive tests; (ii) variance in performance was not explained by the severity of an individual’s overall language impairment alone but was related to two independent behavioural principal components per test; (iii) not all aspects of performance were related to the patient’s language abilities; and (iv) all components were associated with separate neural correlates, some overlapping partly in frontal and parietal regions. Our findings extend our clinical and theoretical understanding of dysfunctions beyond language in patients with aphasia.
24: IDEAL IMPLEMENTATION OF THE MINIMALLY INVASIVE CERVICAL ESOPHAGECTOMY (MICE), A JAPANESE-DUTCH COLLABORATION
Authors: Klarenbeek B , Shiozaki A , Fujiwara H , Rosman C 
Published: April 2022

Abstract

Background and aim
MICE is an innovative Japanese surgical technique, combining a laparoscopic transhiatal and a single port cervical mediastinal dissection in patients operated for esophageal cancer. This complex surgical techniques aims to reduce pulmonary morbidity without compromising oncological radicality by avoiding thoracic access, prevailing pleural integrity and facilitating cervical or abdominal instead of pleural drainage of mediastinal infections in case of anastomotic leakage. Potential drawbacks are an increased risk of recurrent laryngeal nerve injury and learning associated morbidity during the implementation phase. Up to date this technique is not routinely performed in European esophageal cancer patients.

Methods
In order to explore the feasibility and safe implementation of the MICE procedure in Dutch esophageal cancer patients, the evidence based IDEAL-framework will be followed. This framework describes 6 stages of evolution for new surgical therapeutic interventions: Pre-clinical, First in human, Development, Exploration, Assessment and Long-term Study. Outcomes of the first two phases will be described.

Results
The Pre-clinical phase consisted of on-site visits to a Japanese expert center, protocol development, prospective risk assessment, instrument collection and extensive cadaveric training on six fresh frozen human bodies. A ‘virtual supervision platform’ has been developed to proceed with the implementation process despite the COVID pandemic. After thorough evaluation with Dutch upper GI surgical experts and esophageal cancer patients, we have proceeded to the ‘First in Human’ phase.

Conclusion
The IDEAL framework was used as an evidence based tool for safe implementation of the MICE procedure. We will present the results of the ‘pre-clinical’ and ‘first in human’ stage as well as the surgical technique of the MICE procedure.
36: ANASTOMOTIC STRICTURE AFTER IVOR LEWIS OESOPHAGECTOMY—AN EVALUATION OF INCIDENCE, RISK FACTORS AND TREATMENT
Authors: Koshy R , Brown J , Chmelo J , Watkinson T , Phillips A W 
Published: April 2022

Abstract

Background and aim
Anastomotic stricture is a recognised complication after oesophagectomy. It can impact on patient quality of life with some patients requiring multiple dilatations. The aim of this study was to evaluate the frequency of strictures, contributing factors and the long-term outcomes of management in patients undergoing oesophagectomy with thoracic anastomosis using a standardised circular stapled technique.

Methods
All patients who underwent a two-stage transthoracic oesophagectomy with curative intent between January 2010 and December 2019 at the Northern Oesophago-Gastric Unit (NOGU) in Newcastle upon Tyne, UK were included. All patients who underwent a stapled (circular) intrathoracic anastomosis using a gastric conduit were included. Stricture incidence, number of dilatations to treat strictures and refractory stricture rate were recorded.

Results
Overall 705 patients were included with 192 (27.2%) developing strictures. Refractory strictures occurred in 38 patients (5.4%). One, two and three dilatations were needed for resolution of symptoms in 46 (37.4%), 23 (18.7%) and 20 (16.3%) patients respectively. Multivariable analysis identified the occurrence of an anastomotic leak (OR 1.906, 95% CI 1.088–3.341, P = 0.024) and circular stapler size less than 28 mm (OR 1.462, 95% CI 1.033–2.070, P = 0.032) as independent predictors of stricture occurrence. Patients with anastomotic leaks were more likely to develop refractory strictures (13.1% vs. 4.7%, OR 3.089, 95% CI 1.349–7.077, P = 0.008).

Conclusion
This study highlighted that 27.2% of patients having a circular stapled anastomosis required dilatation after surgery. However, most strictures were successfully treated after two dilatations, but 5% of patients had longer-term problems with refractory strictures.
53: SIGNIFICANCE OF NEOADJUVANT DOWNSTAGING IN ADENOCARCINOMA OF THE STOMACH
Authors: Prasad P , Sivaharan A , Navidi M , Phillips A 
Published: April 2022

Abstract

Background and aim
Neoadjuvant chemotherapy is established in the treatment of gastric adenocarcinoma. Histopathological regression as a result of neoadjuvant treatment may have important prognostic implications. There is little data comparing the prognosis of clinical versus pathological stage in patients receiving neoadjuvant treatment. Equally, comparison of outcomes of patients with comparable pathological stage that have received neoadjuvant treatment with those having surgery as their initial treatment is not known. The aim of this study is to determine the impact of neoadjuvant chemotherapy upon the prognosis of patients treated for gastric adenocarcinoma.

Methods
Consecutive patients with gastric cancer from a single, centre between 2007 and 2017 were evaluated. All patients with gastric adenocarcinoma were treated with either a subtotal or total gastrectomy and D2 lymphadenectomy. The impact of downstaging on outcomes and a stage-by-stage comparison of pTNM with ypTNM was performed.

Results
654 patients underwent gastrectomy, 345 patients received neoadjuvant chemotherapy. Patients with downstaged disease had improved overall survival than patients with tumours that did not respond to neoadjuvant chemotherapy (P &lt; 0.001). Downstaging by more than 3 stages was the strongest independent predictor of overall survival when compared with patients who did not respond to neoadjuvant treatment (median survival: 122 vs 66 months, P &lt; 0.001). Survival was significantly improved for patients with advanced overall staging when a stage-wise comparison was performed between patients in like-for-like ypTNM and pTNM groups (ypT 3/4 N2/3 vs pT3/4 N2/3 median survival: 33 vs 16 months, P = 0.001).

Conclusion
Pathological staging following neoadjuvant chemotherapy is better for survival prognostication compared to clinical stage. Downstaging is associated with improved prognosis. There is a significant improvement in survival when comparing pathological stage post neoadjuvant treatment compared to those with a similar stage who had surgical treatment initially.
145: THE USE OF MACHINE LEARNING FOR REAL-TIME DETECTION OF OESOPHAGEAL AND GASTRIC CANCER BASED ON DIFFUSE REFLECTANCE SPECTROSCOPY: A VALIDATION STUDY
Authors: Gkouzionis I , Nazarian S , Kawka M , Peters C , Elson D S 
Published: April 2022

Abstract

Background and aim
The lack of a fast and accurate intraoperative tumour margin assessment tool contributes to high positive circumferential resection margin rates for oesophageal and gastric cancers, which is associated with local recurrence and poor long-term survival. Diffuse reflectance spectroscopy (DRS) can provide non-invasive, accurate, and real-time tissue classification based on quantification of light reflectance in tissue, providing a unique optical fingerprint of the tissue. This study aimed to validate the use of DRS for discrimination between normal and cancerous tissues based on ex-vivo gastric and oesophageal cancer resection specimens.

Methods
Consecutive patients undergoing resections for gastric and oesophageal carcinomas at a tertiary referral centre in London between July 2020 and June 2021 were included. Reflectance data in the 468-720 nm spectral range were recorded on ex-vivo specimens within 15 minutes of surgical specimen excision. Based on video recordings of the data acquisition procedure and probe tip tracking, sampling sites were correlated with histological reports manually labeled as either normal or cancer (Figure 1). Following spectral data normalisation and feature selection, four supervised machine learning approaches were tested for classification using 5-fold cross-validation. Overall classification accuracy and Area Under the Curve (AUC) across machine learning approaches were compared.

Results
A total of 32 patients (median age 68, 75% male) were included. 11,862 mean spectra (2990 spectra for normal oesophagus, 4628 for normal stomach, 2305 for gastric cancer, and 1939 for oesophageal cancer) were collected. For oesophageal cancer, classification accuracy was 96.22 ± 0.50 and AUC was 99.24 ± 0.19, while for gastric cancer, the accuracy was 93.86 ± 0.66, and AUC 98.50 ± 0.28 for gastric cancer. For both malignancy types, Extreme Gradient Boosting was the best performing classifier. The differences in spectral data between patients receiving neoadjuvant treatment and treatment naïve were non-significant.

Conclusion
Machine learning can be used to accurately differentiate between normal and cancerous oesophageal and gastric tissues in an ex-vivo setting, based on DRS data. Features used for class discrimination should be investigated to find possible physiological correlates of spectral data differences. Future intraoperative validation is required to assess the utility of this technology for real-time tumour margin mapping and its effect on long-term outcomes.
189: THE EFFECT OF COVID -19 ON THE NEW DIAGNOSIS OF ESOPHAGOGASTRIC CANCER IN THE UK: A SINGLE-CENTRE EXPERIENCE
Authors: Mcquillan P , Ahmed S , Hayes N , Wahed S , Navidi M , Immanual A , Phillips A 
Published: April 2022

Abstract

Background and aim
Covid-19 has had a devastating global impact and resulted in over 4.4 million directly attributed deaths. The UK entered lockdown in March 2020, redistributing its medical workforce and resources. Early estimations suggested at least 4700 extra cancer deaths at 5 years if there was a 3-month delay to surgery. Delays to diagnosis and treatment for esophagogastric (EG) cancers can be particularly detrimental to survival. The aim of this study is to assess the impact of Covid-19 on new cancer referrals to a centralised UK EG cancer centre, including presentation, decision making and treatment.

Methods
Patients with EG cancer referred to a tertiary, high-volume centre between March 2019 and March 2021 were reviewed. Patients were stratified into Pre-covid (March 2019–March 2020) and Covid (March 2020–2021) cohorts. Number of new referrals, clinical stage, treatment decision, and time to treatment were compared for gastric adenocarcinoma (GA), esophagogastric-junction adenocarcinoma (EGJA), esophageal adenocarcinoma (EA) and esophageal SCC (ESCC).

Results
There was an 11% reduction in new cancer referrals (485 vs 431). GA, EGJA and EA did not have significant change in treatment intent, although there was a significant increase in the decision for definitive non-surgical treatment of EA (P = 0.046). GA and EA patients had a small, but significant increase in average clinical stage at presentation (P &lt; 0.05). There was no increase in time to treatment for GA, EGJA and EA. A significantly higher proportion of ESCC patients were given curative intent treatment in the Covid-19 cohort (P = 0.0006) however, this was accompanied with an increased time to treatment (35.8 days vs 27.9 days P = 0.0198).

Conclusion
This high-volume centre has seen a reduction in new cancer referrals since the first UK lockdown. This was associated with a small, but significant, increase in clinical stage of GA and EA at presentation. This may represent an early indication of excess esophagogastric cancer deaths due to the impact of Covid-19. This data also confirms initial results showing that oncological decisions were not compromised, although Covid-19 remains a dynamic challenge.
Satisfaction With Life and Risk of Dementia: Findings From the Korean Longitudinal Study of Aging
Authors: Zhu Xianghe , Luchetti Martina , Aschwanden Damaris , Sesker Amanda A , Stephan Yannick , Sutin Angelina R , Terracciano Antonio 
Published: April 2022

Abstract

Objectives
Life satisfaction is increasingly viewed as an asset associated with better general health, but its association with cognitive health and risk of dementia is less examined. We tested the hypothesis that higher life satisfaction would be associated with lower risk of dementia.

Methods
Participants were a nationally representative sample of adults (n = 8,021; age range: 45–93 years) from the Korean Longitudinal Study of Aging assessed every 2 years for up to 12 years. Multilevel modeling analysis examined whether life satisfaction is associated with cognitive functioning and decline. The primary analysis used Cox regression to examine the association between baseline life satisfaction and risk of incident dementia.

Results
Between-person differences and within-person changes in life satisfaction were associated with cognitive functioning, but life satisfaction was unrelated to the rate of cognitive decline. Higher life satisfaction was also associated with lower risk of dementia, even after accounting for demographic factors, depressive symptoms, cardiovascular and functional risk factors, health behaviors, and social contact.

Discussion
Satisfaction with life may function as a positive psychological resource for maintaining cognitive functioning and protecting against the risk of dementia.
Geodesics in the Space of m-Subharmonic Functions With Bounded Energy
Authors: Åhag Per , Czyż Rafał 
Published: April 2022

Abstract
We raise our cups to Urban Cegrell, gone but not forgotten, gone but ever here. Until we meet again in Valhalla!
With inspiration from the Kähler geometry, we introduce a metric structure on the energy class, $\mathcal {E}_{1,m}$, of $m$-subharmonic functions with bounded energy and show that it is complete. After studying how the metric convergence relates to the accepted convergences in this Caffarelli–Nirenberg–Spruck model, we end by constructing geodesics in a subspace of our complete metric space.
A small molecule targeting hepatitis B surface antigen inhibits clinically relevant drug-resistant hepatitis B virus
Authors: Kiruthika S , Bhat Ruchika , Jayaram B , Vivekanandan Perumal 
Published: April 2022

Abstract

Background
Currently approved oral antivirals for chronic HBV infection target the reverse transcriptase (RT) domain of the HBV polymerase. Emergence of drug resistance has been reported in a small proportion of chronic HBV patients on prolonged treatment with antivirals. We recently reported ZINC20451377, a small molecule targeting hepatitis B surface antigen (HBsAg) that effectively inhibits both WT HBV and tenofovir-resistant HBV. Due to the partial overlap between the RT domain and HBsAg, drug-resistant mutants are associated with corresponding mutations in HBsAg.

Objectives
To evaluate the efficacy of ZINC20451377 against nine clinically relevant drug-resistant HBV mutants that lead to simultaneous mutations in the overlapping HBsAg gene.

Methods
Huh7 cells were transfected with 1.2× HBV replicons corresponding to WT HBV or drug-resistant HBV mutants and treated with different concentrations of ZINC20451377. We assessed the IC50 values of ZINC20451377 for HBsAg levels in the culture supernatants using ELISAs. HBV secretion was measured by immunocapture of secreted virions followed by real-time PCR quantitation of virion-associated DNA.

Results
ZINC20451377 led to a dose-dependent inhibition of secreted HBsAg encoded by WT HBV and all nine drug-resistant mutants tested and the IC50 values were in the low micromolar range. ZINC20451377 inhibited HBV secretion from drug-resistant mutants except for mutants harbouring the rtL180M + rtM204V (MV) mutation.

Conclusions
The small molecule ZINC20451377 inhibits HBsAg and virion secretion in some of the clinically relevant drug-resistant HBV mutants. ZINC20451377 has a modest overall effect, and it was not effective against the MV mutants (lamivudine- and entecavir-resistant mutants).
Evidence for Multiple Origins of Knockdown Resistance (kdr) in Spodoptera exigua (Hübna) (Lepidoptera: Noctuidae) From China
Authors: Zuo Yayun , Wang Zeyu , Ren Xuan , Pei Yakun , Aioub Ahmed A A , Hu Zhaonong 
Published: April 2022

Abstract
The beet armyworm, Spodoptera exigua (Hübna) is a serious agricultural pest that is challenging to control due to resistance to most pesticides, including pyrethroids. This resistance has previously been linked to the knockdown resistance (kdr) mutation (L1014F) of the voltage-gated sodium channel (VGSC) in S. exigua. To better understand the frequencies of the kdr mutation of SeVGSC and identify the evolutionary origins of kdr mutation in S. exigua, seven populations of S. exigua were collected in China, and partial SeVGSC genomic sequences for each individual were acquired. The bioassays showed that the survival rates of seven populations of S. exigua larvae exposed to the discriminating dose of beta-cypermethrin (0.05 mg/cm2) ranged from 91.66% to 100%, indicating that all seven populations had evolved resistance to beta-cypermethrin. The frequencies of kdr mutation (CTT to TTT) of SeVGSC of field populations ranged China were from 60% to 89.6%. The CTT to CAT substitution at this coding position resulting in the L1014H (kdr-H) mutation was found in only one individual from the QP18 population. Based on the phylogeny of SeVGSC alleles, it appeared that the kdr mutation in S. exigua populations had multiple origins, which has major consequences for pyrethroid effectiveness in the field. Thus, it is recommended to limit the use of pyrethroid and encourage rotation of insecticides with different modes of action for control of S. exigua to alleviate resistance development.
Indirect Investor Protection: The Investment Ecosystem and Its Legal Underpinnings
Authors: Spamann Holger 
Published: April 2022

Abstract
This article argues that the key mechanisms protecting portfolio investors in public corporate securities are indirect. They do not rely on actions by the investors or by any private actor charged with looking after investors’ interests. Rather, they are provided by the ecosystem that investors (are legally forced to) inhabit, as a byproduct of the self-interested, mutually and legally constrained behavior of third parties without a mandate to help the investors such as speculators, activists, and plaintiff lawyers. This elucidates key rules, resolves the mandatory versus enabling tension in corporate/securities law, and exposes the current system’s fragile reliance on trading.
Establishing the Content Validity of a Modified Bank of School Anxiety Inventory Items for Use Among Adolescents With Chronic Pain
Authors: Gibler Robert C , Abelson Elana , Williams Sara E , Lynch-Jordan Anne M , Kashikar-Zuck Susmita , Jastrowski Mano Kristen E 
Published: April 2022

Abstract

Objective
School anxiety is a prevalent mental health concern that drives school-related disability among youth with chronic pain. The only available measure of school anxiety—the School Anxiety Inventory, Short Version (SAI-SV)—lacks content specificity for measuring school anxiety in pediatric pain populations. We aimed to refine the SAI-SV by obtaining qualitative data about unique school situations that are anxiety-provoking for youth with pain and characterizing the nature of symptoms experienced in these situations.

Methods
Adolescents with chronic pain (n = 16) completed a semistructured interview focused on experiences with anxiety in school-related academic and social contexts. We employed thematic analysis to extend the empirical understanding of school anxiety from the perspective of patients suffering from pain and to generate new item content. The content was refined with iterative feedback from a separate group of adolescents with chronic pain (n = 5) and a team of expert pain psychologists (n = 3).

Results
We identified six themes within the data and generated new items designed to capture anxiety related to negative interactions with teachers and peers, falling behind with schoolwork, and struggles with concentration and fatigue. Participants and experts rated new item content as highly relevant for use among youth with pain. The updated item bank was named the School Anxiety Inventory for Chronic Pain.

Conclusions
Future research is needed to complete the psychometric evaluation of the item bank and finalize items to be included in a measure that can be used in research and clinical settings. Implications for treating school-related anxiety among youth with pain are also discussed.