bluuebunny/crossref_metadata_2025 huggingface dataset:
A study on the effect of surface topography of antifouling coatings on the settlement of fouling organisms
Authors: Kardar Pooneh , Amini Reza
Published: November 2022

Purpose

The purpose of this paper is to study the correlation between different topographies and the reaction of Ulva Linza fouling species.

Design/methodology/approach

In this research, topographies with a different method, such as hot embossing and hot pulling, were achieved, and biological analyses were done with macroalgae Ulva Linza cells. The effect of topography via local binding geometry (honeycomb size gradients) and Wenzel roughness on the settling of Ulva microorganisms was tested.

Findings

As a result, Ulva spores confirmed different reactions to a similar set of tapered microstructures that was in agreement with the results on distinct honeycombs. The local binding geometry and the Wenzel roughness factor “r” were dominant on settling of Ulva Linza spores.

Research limitations/implications

The reaction of an organism at the interface of vehicles’ substrate is powerfully affected by surface topographies.

Practical implications

The best embedment occurred on structures with bigger sizes than Ulva Linza’s spores. The density of settled spores was proportional to Wenzel roughness and the spores favour to attach to “kink sites” positions.

Social implications

Unfortunately, unpleasant aggregation of marine biofouling on marine vehicles’ surfaces, generate terrific difficulties in the relevant industry.

Originality/value

There was a sharp relationship between Wenzel roughness and settle of Ulva Linza spores. The local binding geometry and the Wenzel roughness factor “r” were dominant on settling of Ulva Linza spores.
Electrical resistivity tomography and ground‐penetrating radar methods to detect archaeological walls of Babylonian houses near Ishtar temple, ancient Babylon city, Iraq
Authors: AL‐Hameedawi Mohammed M. , Thabit Jassim M. , AL‐Menshed Firas H.
Published: November 2022

A survey was conducted to investigate buried archaeological walls near the Ishtar temple in the ancient Babylon city using electrical resistivity tomography and ground‐penetrating radar methods. The survey includes applying 12 electrical resistivity tomography profiles using dipole–dipole array and a ground‐penetrating radar grid of 55 m × 50 m using 250 MHz antenna. Although the buried walls are consisting of mudbrick masonry and are embedded in a clayey environment, the electrical resistivity tomography method is still able to differentiate the tiny differences between the host materials and the buried walls, which show distinctive wall‐like features with resistivity values ranging between 9 and 15 Ω m. These features may reflect underground‐buried walls with a general width reaching about 2.5 m. The comparison of ground‐penetrating radar profiles and their corresponding electrical resistivity tomography profiles presents that the main architectures are coinciding well. The analysis of the geometry and composition of the walls around the Ishtar temple suggested that the wall‐like reflections on the ground‐penetrating radar slice at a depth between 140 and 150 cm (may be shallower) are underground‐buried walls. These wall‐like reflections show a special trend and orientation that indicate that they may be the remains of rooms belonging to two small houses or the remains of one big private house.
Warmer temperatures are linked to widespread phenological mismatch among native and non‐native forest plants
Authors: Miller Tara K. , Heberling J. Mason , Kuebbing Sara E. , Primack Richard B.
Published: November 2022

Deciduous trees, shrubs and forest wildflowers may be advancing their leaf‐out phenology at different rates in response to a warming climate. A mismatch between understory and overstory phenology may lead to a reduction of understory light levels in the early spring, which is a critical period when many spring‐blooming wildflowers achieve highest photosynthetic rates. However, the extent of this phenomenon beyond a single site or region is largely unknown.

Using 3083 herbarium specimens collected between 1870 and 2019 across eastern North America, we assessed leaf‐out and flowering times of 10 tree species (6 native, 4 non‐native), 4 shrub species (2 native, 2 non‐native) and 7 wildflower species (6 native, 1 non‐native). We paired phenological data with historical climate data to quantify differences in phenological sensitivity to spring temperature across canopy strata, across species' geographical ranges and between native and non‐native species.

Predicted phenological mismatches between native trees and wildflowers differed across large spatial scales, with wildflower populations in warmer regions of North America more likely to be affected. Overall, native tree species leafed out 3.6 days earlier per °C spring warming, while native wildflower species advanced their flowering times by 3.2 days per °C, resulting in phenological mismatch as wildflowers experience fewer days before tree leaf‐out at warmer temperatures. Native trees and wildflowers in the warmer, southern part of their ranges advanced their spring phenology 2 and 1.5 times faster, respectively, than those in colder, northern locations. The phenological sensitivity of non‐native plants was less variable across their ranges. Non‐native trees and shrubs exhibited greater phenological sensitivity than native wildflowers. Notably, phenological sensitivities differed substantially among wildflower species, suggesting that certain species are more likely to be affected by phenological mismatch as climate warming progresses.

Synthesis: Our results provide new insight into novel phenological responses within and among species across a wide geographical range and the potential impact of competition and interactions with non‐native invasive species. This research highlights the value of newly‐available digitized museum collections in phenological research to cover longer time periods, wider spatial areas and a greater diversity of species than otherwise possible.
Hormone replacement cycles are associated with a higher risk of hypertensive disorders: Retrospective cohort study in singleton and twin pregnancies
Authors: Pape Janna , Levy Jérémy , von Wolff Michael
Published: November 2022

Objective

To elaborate the associations of different cycle regimens (natural cycle [NC], stimulated cycle [SC], hormone replacement cycle [HRC]) on maternal and neonatal adverse pregnancy outcomes after frozen–thawed embryo transfers (FET).

Design

Population‐based registry study.

Setting

Swiss IVF Registry.

Population or Sample

Singleton (n = 4636) and twin (n = 544) live births after NC‐FET (n = 776), SC‐FET (n = 758) or HRC‐FET (n = 3646) registered from 2014 to 2019.

Methods

Fifteen pregnancy pathologies were modelled for singleton and twin pregnancies using mixed models adjusted for cycle regimen, delivery, fertilisation technique, chronic anovulation, age of mother and centre.

Main outcome measures

Maternal (vaginal bleeding, isolated arterial hypertension and pre‐eclampsia) and neonatal (gestational age, birthweight, mode of delivery) adverse pregnancy outcomes.

Results

In singleton pregnancies, the incidences of bleeding in first trimester, isolated hypertension and pre‐eclampsia were highest in HRC‐FET with doubled odds of bleeding in first trimester (adjusted odds ratio [aOR] 2.23; 95% CI 1.33–3.75), isolated hypertension (aOR 2.50; 95% CI 1.02–6.12) and pre‐eclampsia (aOR 2.16; 95% CI 1.13–4.12) in HRC‐FET vs. NC‐FET and with doubled respectively sixfold odds of bleeding (aOR 2.08; 95% CI 1.03–4.21) and pre‐eclampsia (6.02; 95% CI 1.38–26.24) in HRC‐FET versus SC‐FET. In twin pregnancies, the incidence of pre‐eclampsia was highest in HRC‐FET with numerically higher odds of pre‐eclampsia in HRC‐FET versus NC‐FET and versus SC‐FET.

Conclusions

Our data implied the highest maternal risks of hypertensive disorders in HRC‐FET, therefore clinicians should prefer SC‐FET or NC‐FET if medically possible.
Dityrosine in food: A review of its occurrence, health effects, detection methods, and mitigation strategies
Authors: Li Bowen , Yang Yuhui , Ding Yinyi , Ge Yueting , Xu Yuncong , Xie Yanli , Shi Yonghui , Le Guowei
Published: November 2022

Protein and amino acid oxidation in food products produce many new compounds, of which the reactive and toxic compound dityrosine, derived from oxidized tyrosine, is the most widely studied. The high reactivity of dityrosine enables this compound to induce oxidative stress and disrupt thyroid hormone function, contributing to the pathological processes of several diseases, such as obesity, diabetes, cognitive dysfunction, aging, and age‐related diseases. From the perspective of food safety and human health, protein‐oxidation products in food are the main concern of consumers, health management departments, and the food industry. This review highlights the latest research on the formation pathways, toxicity, detection methods, occurrence in food, and mitigation strategies for dityrosine. Furthermore, the control of dityrosine in family cooking and food‐processing industry has been discussed. Food‐derived dityrosine primarily originates from high‐protein foods, such as meat and dairy products. Considering its toxicity, combining rapid high sensitivity dityrosine detection techniques with feasible control methods could be an effective strategy to ensure food safety and maintain human health. However, the current dityrosine detection and mitigation strategies exhibit some inherent characteristics and limitations. Therefore, developing technologies for rapid and effective dityrosine detection and control at the industrial level is necessary.
Occupational Mobility in the ALife Data: How Reliable are Occupational Patterns from Administrative Australian Tax Records?*
Authors: Hathorne Clara , Breunig Robert
Published: November 2022

The purpose of this paper is to compare the distribution of occupation and rates of occupational mobility in the ATO Longitudinal Information Files (ALife) and the Household, Income and Labour Dynamics in Australia (HILDA) datasets. As tax is not occupation dependent, occupation data from tax records may not be reliable. We find that occupational mobility in the ALife data is less than half that in the nationally representative HILDA data. In contrast, the distribution of occupation and its relationship with most key socio‐economic characteristics appear relatively similar across the two datasets. However, occupation evolves differently over time in the two datasets and there are some differences between the sexes.
The T stage of esophageal cancer can be effectively predicted by muscularis propria thickness and muscularis propria + mucosa thickness under ultrasonic gastroscopy
Authors: Yu Yongkui , Wei Xiufeng , Chen Xiankai , Li Haomiao , Liu Qi , Sun Haibo , Wang Wei , Wang Lifeng , Li Yin , Xing Wenqun
Published: November 2022

Objectives

The latest version of the National Comprehensive Cancer Network recommends neoadjuvant therapy followed by surgical treatment or radical chemoradiotherapy for patients with cT3N0M0. Neoadjuvant therapy can improve the prognosis of patients with locally advanced esophageal cancer. Therefore, the evaluation or prediction of T stage is particularly important because the treatment could differently affect the prognosis. Here, we establish a model to predict the T stage of patients with T2‐3N0M0 to help choose the best treatment strategy.

Methods

From 1637 patents with esophageal cancer, we enrolled 48 patients and performed least absolute shrinkage and selection operator regression to screen for independent factors influencing pathological T stage. We, then, trained the decision tree to obtain the decision tree diagram and divided the T stages obtained by different methods into two categories, T2 and T3, for survival analysis.

Results

A total of 21 and 27 cases were predicted to be T2 and T3, respectively, under ultrasonic gastroscopy, 19 and 29 under magnetic resonance imaging, and 22 and 26 under pathological examination. Multivariate logistic regression analysis revealed that the muscularis propria thickness (MPT) (p = 0.0097) and the muscularis propria + mucosa thickness (MPMT) in the largest tumor cross‐section (p = 0.0239) were independent influencing factors. We plotted a decision tree diagram with these two factors. MPT in the largest tumor cross‐section >1.3 mm could be judged as pT3; if ≤1.3 mm, MPMT should be considered a thickness ≥1.7 mm could be judged as pT2 (otherwise pT3). Corresponding survival analysis was performed according to the T stage under different examination modalities.

Conclusion

MPT in the largest tumor cross‐section and MPMT in the largest tumor cross‐section are independent predicting factors of pathological T stage.
Developing nondestructive species‐specific tree allometry with terrestrial laser scanning
Authors: Stovall Atticus E. L. , Vorster Anthony , Anderson Ryan , Evangelista Paul
Published: November 2022

Allometric equations predict organism attributes from simple measurements and underlie many global‐scale estimates, from plant productivity to ecosystem carbon stocks. In forests, destructive harvesting of trees in common groups (e.g. plant functional type) or at the species level is necessary to develop allometry but, since sampling is extremely difficult, predictions from these equations have high uncertainty due to low sample size, spatial bias and unrepresentative sampling of tree size. Terrestrial laser scanning (TLS) is a promising remote sensing technology that enables efficient and nondestructive estimates of tree‐level structure for developing allometric equations.

Here, we nondestructively estimated component biomass of three coniferous tree species (Pinus ponderosa, Pinus contorta and Pseudotsuga menziesii) in Colorado, USA using TLS. We evaluated the suitability for this nondestructive data to be supplanted for destructive data in the development of species‐specific allometric equations and compared the prediction accuracy against a commonly used national‐scale allometry.

We found TLS biomass estimates were consistently more precise across species (RMSE = ~19%) than nation‐scale allometry (RMSE = ~39%). Nondestructive biomass estimates from TLS are a suitable addition to or replacement for traditional sampling methods, with indistinguishable biomass predictions across most of the tested diameter range. We further show how TLS can be used to develop allometric equations compatible with airborne LiDAR and other remote sensing variables (e.g. height and crown area), developing generalized biomass predictions from crown area and tree height (R2 = 0.87).

The ability for TLS to support the development of nondestructive allometry at a global scale will enable a more nuanced understanding of the drivers of individual tree architecture, while supporting the next generation of biomass remote sensing.
Lack of amygdala habituation to negative emotional faces in alcohol use disorder and the relation to adverse childhood experiences
Authors: Gerhardt Sarah , Berhe Oksana , Moessnang Carolin , Horning Maibritt , Kiefer Falk , Tost Heike , Vollstädt‐Klein Sabine
Published: November 2022

Aberrant limbic circuit reactivity to negative stimuli might be related to alterations in emotion processing and regulation in alcohol use disorder (AUD). The current study tested for the first time in AUD the hypothesis of aberrant amygdala habituation to repeated aversive stimuli—a robust and reliable neuroimaging marker for emotion processing. We explored the link between deficits in habituation to adverse childhood experience (ACE), a common risk factor for impaired emotion regulation and AUD. AUD individuals (N = 36) and healthy controls (HC; N = 26) participated in an observational case–control functional magnetic resonance imaging (fMRI) study. An established habituation index was used to investigate processing of aversive emotional faces of the amygdala. AUD individuals showed an overall deficit in amygdala habituation (right: t = 4.26, pFWE = 0.004; left: t = 4.79, pFWE ≤ 0.001). Amygdala habituation was significantly related to increased exposure to ACE in HC (t = 3.88, pFWE = 0.012), whereas this association was not observed in AUD individuals (T = 1.80, pFWE = 0.662). Further, a significant association between higher alcohol consumption and reduced amygdala habituation (right: R2 = −0.356, F = 8.736, p = 0.004; left: R2 = −0.309, F = 6.332, p = 0.015) was observed. We found novel evidence for neural alterations in emotion processing in AUD individuals, indexed by deficient amygdala habituation to negative emotional content. We replicated a prior report on a link between ACE and amygdala habituation, a well‐established environmental risk factor for mental disorders and emotion dysregulation, in our control sample. Additionally, deficient amygdala habituation related to the amount of alcohol consumption in the overall sample might indicate a short‐term substance effect.
Carer‐reported measures for a dementia registry: A systematic scoping review and a qualitative study
Authors: Lin Xiaoping , Ward Stephanie A. , Pritchard Elizabeth , Ahern Susannah , Gardam Madeleine , Brodaty Henry , Ryan Joanne , McNeil John , Tsindos Tess , Wallis Kasey , Jeon Yun‐Hee , Robinson Sandra , Krysinska Karolina , Ayton Darshini
Published: November 2022

Objectives

Informal carers play a critical role in supporting people with dementia. We conducted a scoping review and a qualitative study to inform the identification and development of carer‐reported measures for a dementia clinical quality registry.

Methods

Phase 1—Scoping review: Searches to identify carer‐reported health and well‐being measures were conducted in three databases (MEDLINE, PsycINFO and Embase). Data were extracted to record how the measures were administered, the domains of quality‐of‐life addressed and whether they had been used in a registry context. Phase 2—Qualitative study: Four focus groups were conducted with carers to examine the acceptability of selected measures and to identify outcomes that were important but missing from these measures.

Results

Phase 1: Ninety‐nine carer measures were identified with the top four being the Zarit Burden Interview (n = 39), the Short‐Form12/36 (n = 14), the Brief Coping Orientation to Problems Experienced scale and the Sense of Coherence scale (both n = 9). Modes of administration included face‐to‐face (n = 50), postal (n = 11), telephone (n = 8) and online (n = 5). No measure had been used in a registry context. Phase 2: Carers preferred brief measures that included both outcome and experience questions, reflected changes in carers' circumstances and included open‐ended questions.

Conclusions

Carer‐reported measures for a dementia clinical quality registry need to include both outcome and experience questions to capture carers' perceptions of the process and outcomes of care and services. Existing carer‐reported measures have not been used in a dementia registry context and adaption and further research are required.
Behavior change training for pregnant women's communication during birth: A randomized controlled trial
Authors: Derksen Christina , Dietl Johanna Elisa , Haeussler Freya Elise , Steinherr Zazo Miriam , Schmiedhofer Martina , Lippke Sonia
Published: November 2022

Applying health psychological theories can improve communication interventions to empower pregnant women and ensure safe births. The aim was to test a short digital communication intervention based on the health action process approach. A randomized‐controlled trial was conducted with pregnant women at two German university hospitals. The intervention group (NT1 = 225; NT2 = 142) received a 2.5 h online training focusing on communication planning, self‐efficacy and communicating personal needs and preferences under difficult circumstances. This group was compared with a passive control group (NT1 = 199; NT2 = 144). Data from the N = 286 women with complete datasets were used for multilevel analyses. Data from all recruited N = 424 women were used for intention‐to‐treat analyses with multiple imputation. Both groups improved regarding communication behavior, quality of birth, action planning, coping planning and coping self‐efficacy after birth, which was more pronounced in the intervention group. The intention‐to‐treat analyses confirmed the higher improvement for communication behavior, perceived quality of birth and coping planning. The intervention was related to improvements in pregnant women's communication behavior and quality of birth. Hence, future research and practice should apply and evaluate health psychological theories when targeting communication and empowerment.
Synchronous vs independent reading of prostate‐specific membrane antigen positron emission tomography (PSMA‐PET) and magnetic resonance imaging (MRI) to improve diagnosis of prostate cancer
Authors: Doan Paul , Counter William , Papa Nathan , Sheehan‐Dare Gemma , Ho Bao , Lee Jonathan , Liu Victor , Thompson James E. , Agrawal Shikha , Roberts Matthew J. , Buteau James , Hofman Michael S. , Moon Daniel , Lawrentschuk Nathan , Murphy Declan , Stricker Phillip D. , Emmett Louise
Published: November 2022

Objectives

To identify whether synchronous reading of multiparametric magnetic resonance imaging (mpMRI) and 68Ga‐PSMA‐11 positron emission tomography (PET)/computed tomography (prostate‐specific membrane antigen [PSMA‐PET]) images can improve diagnostic performance and certainty compared with mpMRI/PSMA‐PET reported independently and synthesized, while also assessing concordance between imaging modalities and agreement with histopathology.

Methods

This was a retrospective analysis of 100 patients randomly selected from the PRIMARY trial, a prospective Phase II multicentre imaging trial. Three dual‐trained radiologist/nuclear medicine physicians re‐reported the mpMRI and PSMA‐PET both independently and synchronously for the same patients in random order, blinded to previous results. Diagnostic performance was assessed for mpMRI/PSMA‐PET images read synchronously or independently and then synthesized. Agreement between imaging results and histopathology was examined. ‘Concordance’ between imaging modalities was defined as overlapping lesions. Reporting certainty was evaluated by the individual reporters for each modality.

Results

International Society of Urological Pathology Grade Group ≥2 cancer was present in 60% of patients on biopsy. Synchronous reading of mpMRI/PSMA‐PET increased sensitivity compared to mpMRI or PSMA‐PET alone (93% vs 80% vs 88%, respectively), although specificity was not improved (63% vs 58% vs 78%, respectively). No significant difference in diagnostic performance was noted between mpMRI/PSMA‐PET read synchronously and mpMRI or PSMA‐PET reported independently and then synthesized. Most patients had concordant imaging (60%), while others had discordant lesions only (28%) or a mixture (concordant and discordant lesions; 12%). When mpMRI/PSMA‐PET findings were concordant and positive, 95% of patients had clinically significant prostate cancer (csPCa). When PSMA‐PET alone was compared to synchronous PSMA‐PET/MRI reads, there was an improvement in reader certainty in 20% of scans.

Conclusion

Synchronous mpMRI/PSMA‐PET reading improves reader certainty and sensitivity for csPCa compared to mpMRI or PSMA‐PET alone. However, synthesizing the results of independently read PSMA‐PET and mpMRI reports provided similar diagnostic performance to synchronous PSMA‐PET/MRI reads. This may provide greater flexibility for urologists in terms of referral patterns, reducing healthcare system costs and improving efficiencies in prostate cancer diagnosis.
Rift kinematics preserved in deep‐time erosional landscape below the northern North Sea
Authors: Wrona Thilo , Whittaker Alexander C. , Bell Rebecca E. , Gawthorpe Robert L. , Fossen Haakon , Jackson Christopher A.‐L. , Bauck Marit Stokke
Published: November 2022

Our understanding of continental rifting is, in large parts, derived from the stratigraphic record. This record is, however, incomplete as it does not often capture the geomorphic and erosional signal of rifting. New 3D seismic reflection data reveal a Late Permian‐Early Triassic landscape incised into the pre‐rift basement of the northern North Sea. This landscape, which covers at least 542 km2, preserves a drainage system bound by two major tectonic faults. A quantitative geomorphic analysis of the drainage system reveals 68 catchments, with channel steepness and knickpoint analysis of catchment‐hosted palaeo‐rivers showing that the landscape preserved a >2 Myr long period of transient tectonics. We interpret that this landscape records a punctuated uplift of the footwall of a major rift‐related normal fault (Vette Fault) at the onset of rifting. The landscape was preserved by a combination of relatively rapid subsidence in the hangingwall of a younger fault (Øygarden Fault) and burial by post‐incision sediments. As such, we show how and why erosional landscapes are preserved in the stratigraphic record, and how they can help us understand the tectono‐stratigraphic evolution of ancient continental rifts.
Mitochondrial DNA haplogroup M7: A predictor of poor prognosis for colorectal cancer patients in Chinese population
Authors: Yan Zeyu , Yuan Qing , He Yiwei , Peng Fan , Liu Yang , Zhang Huanqin , Ji Xiaoying , He Xianli , Zhao Qi , Xing Jinliang , Guo Xu
Published: November 2022

Haplogroups and single‐nucleotide polymorphisms (SNP) of mitochondrial DNA (mtDNA) were associated with the prognosis of many types of cancer patients. However, whether mtDNA haplogroups contribute to clinical outcomes of colorectal cancer (CRC) in Chinese population remains to be determined. In this study, mtDNA of tissue samples from 445 CRC patients from Northwestern China was sequenced to evaluate the association between haplogroup and prognosis. The mtDNA sequencing data of 1015 CRC patients from Southern China were collected for validation. We found patients with mtDNA haplogroup M7 had a significantly higher death risk when compared with patients with other haplogroups in both Northwestern (Hazard ratio [HR] = 3.093, 95% CI = 1.768–5.411, p < 0.001) and Southern (HR = 1.607, 95% CI = 1.050–2.459, p = 0.029) China. Then, a haplogroup M7–based mtSNP classifier was selected by using LASSO Cox regression analysis. A nomogram comprising the mtSNP classifier and clinicopathological variables was developed to predict the prognosis of CRC patients (area under the curve [AUC] 0.735, 95% CI = 0.679–0.791). Furthermore, patients with high‐ and low‐risk scores calculated by the haplogroup M7–based mtSNP classifier exhibited significantly different overall survival (OS) and recurrence‐free survival (RFS) (all p < 0.001). Finally, RNA‐seq and immunohistochemical analyses indicated the poor prognosis of patients with haplogroup M7 may be related to mitochondrial dysfunction and immune abnormalities in CRC tissues. In conclusion, the haplogroup M7 and haplogroup M7–based mtSNP classifier seems to be a practical and reliable prognostic predictor for CRC patients, which provides a potential tool of clinical decision‐making for patients with haplogroup M7 in Chinese population.
Identification of odontogenic ameloblast associated as a novel target gene of the Wnt/β‐catenin signaling pathway
Authors: Yamaguchi Kiyoshi , Horie Chiaki , Takane Kiyoko , Ikenoue Tsuneo , Nakagawa Saya , Isobe Yumiko , Ota Yasunori , Ushiku Tetsuo , Tanaka Mariko , Fujishiro Jun , Hoshino Noriko , Arisue Atsuhiro , Nishizuka Satoshi , Aikou Susumu , Shida Dai , Furukawa Yoichi
Published: November 2022

The Wnt/β‐catenin signaling pathway plays a key role in development and carcinogenesis. Although some target genes of this signaling have been identified in various tissues and neoplasms, the comprehensive understanding of the target genes and their roles in the development of human cancer, including hepatoma and colorectal cancer remain to be fully elucidated. In this study, we searched for genes regulated by the Wnt signaling in liver cancer using HuH‐7 hepatoma cells. A comparison of the expression profiles between cells expressing an active form of mutant β‐catenin and cells expressing enhanced green fluorescent protein (EGFP) identified seven genes upregulated by the mutant β‐catenin gene (CTNNB1). Among the seven genes, we focused in this study on ODAM, odontogenic, ameloblast associated, as a novel target gene. Interestingly, its expression was frequently upregulated in hepatocellular carcinoma, colorectal adenocarcinoma, and hepatoblastoma. We additionally identified a distant enhancer region that was associated with the β‐catenin/TCF7L2 complex. Further analyses revealed that ODAM plays an important role in the regulation of the cell cycle, DNA synthesis, and cell proliferation. These data may be useful for clarification of the main molecular mechanism(s) underlying these cancers.
Dual targeted therapy with pyrotinib and trastuzumab forHER2‐positive advanced colorectal cancer: A phase 2 trial
Authors: Fu Xianhua , Ying Jieer , Yang Liu , Fang Weijia , Han Weidong , Hu Hanguang , Zhang Suzhan , Yuan Ying
Published: November 2022

This trial was initiated to evaluate the efficacy and safety of pyrotinib in combination with trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)‐positive recurrent/metastatic colorectal cancer (CRC). In this single‐arm, open‐label, multicenter, phase 2 trial patients with HER2‐positive recurrent/metastatic CRC were enrolled and received oral pyrotinib 400 mg once a day plus intravenous trastuzumab 8 mg/kg loading dose followed by 6 mg/kg once every 3 weeks. The primary endpoint was the objective response rate (ORR). Disease control rate (DCR), progression‐free survival (PFS), duration of response, and safety were assessed as secondary endpoints. From December 2019 to October 2021, a total of 20 patients were enrolled and 18 of them were evaluable for response. All patients were B‐rapidly accelerated fibrosarcoma (BRAF) wild type. Four patients achieved partial response, with an ORR of 22.2% (4/18, 95% confidence interval [CI] 6.4–47.6) and DCR of 61.1% (11/18, 95% CI 35.8–82.7), while the ORR and DCR were 33.3% (4/12, 95% CI 13.8–60.9) and 83.3% (10/12, 95% CI 51.6–97.9), respectively, inRASwild‐type patients. At the time of cut‐off day, median follow‐up was 10.7 months (range 3.8–13.8). The median PFS was 3.4 months (95% CI 1.8–4.3) in the overall population and 4.3 months (95% CI 3.2–8.5) in theRASwild‐type group. The most common adverse event of grade ≥3 was diarrhea (13/20, 65.0%). Pyrotinib combined with trastuzumab showed promising antitumor activity and a manageable safety profile in patients withRAS/BRAFwild‐type HER2‐positive advanced CRC.
Putative founder effect of Arg338* AP4M1 (SPG50) variant causing severe intellectual disability, epilepsy and spastic paraplegia: Report of three families
Authors: Becker Aurélie , Felici Charlotte , Lambert Laëtitia , de Saint Martin Anne , Abi‐Warde Marie‐Thérèse , Schaefer Elise , Zix Christian , Zamani Mina , Sadeghian Saeid , Zeighami Jawaher , Seifi Tahereh , Azizimalamiri Reza , Shariati Gholamreza , Galehdari Hamid , Selig Mareike , Ding Can , Duerinckx Sarah , Pirson Isabelle , Abramowicz Marc , Clément Guillemette , Leheup Bruno , Jonveaux Philippe , Lefort Geneviève , Bronner Myriam , Renaud Mathilde , Bonnet Céline
Published: November 2022

Bi‐allelic variants affecting one of the four genes encoding the AP4 subunits are responsible for the “AP4 deficiency syndrome.” Core features include hypotonia that progresses to hypertonia and spastic paraplegia, intellectual disability, postnatal microcephaly, epilepsy, and neuroimaging features. Namely, AP4M1 (SPG50) is involved in autosomal recessive spastic paraplegia 50 (MIM#612936). We report on three patients with core features from three unrelated consanguineous families originating from the Middle East. Exome sequencing identified the same homozygous nonsense variant: NM_004722.4(AP4M1):c.1012C>T p.Arg338* (rs146262009). So far, four patients from three other families carrying this homozygous variant have been reported worldwide. We describe their phenotype and compare it to the phenotype of patients with other variants in AP4M1. We construct a shared single‐nucleotide polymorphism (SNP) haplotype around AP4M1 in four families and suggest a probable founder effect of Arg338* AP4M1 variant with a common ancestor most likely of Turkish origin.
Can cooperatives help commercial farms to access credit in China? Evidence from Jiangsu Province
Authors: Peng Yuanyuan , Wang H. Holly , Zhou Yueshu
Published: November 2022

Chinese agriculture is experiencing a transition from smallholder farming to the emergence of commercial farms that are characterized by intensification and specialization in production, as well as commercialization and cooperation in management. It requires substantial capital to facilitate such a transition, but it is very difficult for farmers in China to access bank credit. One way that commercial farms have to overcome such handicap is by organizing themselves into cooperatives. To assess the effect of cooperatives on the credit accessibility of commercial farms, we have developed a theoretical model as well as an empirical study of commercial farms in Jiangsu Province based on data from a survey of 754 commercial farm owners. Instrumental variable (IV) methods and the Propensity Score Matching (PSM) method that control endogeneity problem are used in the analysis. The empirical results show that cooperatives have a significant positive impact on the credit access of commercial farms. Commercial farms participating in cooperatives may alleviated their credit constraints by about 17.3 percentage points and increase the average credit per capita by nearly 80,000 Yuan. Cooperatives improve the credit access of commercial farms by exerting strong market power and reputation effect based on its organizational advantages. A disaggregated analysis also reveals that small commercial farms tend to benefit more from cooperatives in improving credit access than large commercial farms.
Empowering drug development: Leveraging insights from imaging technologies to enable the advancement of digital health technologies
Authors: Izmailova Elena S. , Maguire R. Paul , McCarthy Timothy J. , Müller Martijn L. T. M. , Murphy Philip , Stephenson Diane
Published: November 2022

The US Food and Drug Administration (FDA) has publicly recognized the importance of improving drug development efficiency, deeming translational biomarkers a top priority. The use of imaging biomarkers has been associated with increased rates of drug approvals. An appropriate level of validation provides a pragmatic way to choose and implement these biomarkers. Standardizing imaging modality selection, data acquisition protocols, and image analysis (in ways that are agnostic to equipment and algorithms) have been key to imaging biomarker deployment. The best known examples come from studies done via precompetitive collaboration efforts, which enable input from multiple stakeholders and data sharing. Digital health technologies (DHTs) provide an opportunity to measure meaningful aspects of patient health, including patient function, for extended periods of time outside of the hospital walls, with objective, sensor‐based measures. We identified the areas where learnings from the imaging biomarker field can accelerate the adoption and widespread use of DHTs to develop novel treatments. As with imaging, technical validation parameters and performance acceptance thresholds need to be established. Approaches amenable to multiple hardware options and data processing algorithms can be enabled by sharing DHT data and by cross‐validating algorithms. Data standardization and creation of shared databases will be vital. Pre‐competitive consortia (public‐private partnerships and professional societies that bring together all stakeholders, including patient organizations, industry, academic experts, and regulators) will advance the regulatory maturity of DHTs in clinical trials.
Dermatofibrosarcoma protuberans im Gesicht: Klinisch‐pathologische und molekulare Studie mit 34 Fällen
Authors: Han Qianqian , Chen Min , Yang Jieliang , Du Tianhai , Peng Heng
Published: November 2022

Hintergrund

Dermatofibrosarcoma protuberans (DFSP) ist eines der häufigsten dermalen Sarkome, kommt aber im Gesicht nur selten vor.

Patienten und Methoden

Die klinisch‐pathologischen Charakteristika von insgesamt 34 fazialen DFSP wurden näher untersucht. Hierzu wurden zusätzlich eine Immunmarkierung (CD34) sowie eine PDGFB/COL1A1‐PDGFB Fluoreszenz‐in situ‐Hybridisierung (FISH) durchgeführt.

Ergebnisse

Die untersuchten Patienten waren zwischen 24 und 64 Jahre alt (im Mittel 42,9 Jahre), das Verhältnis Mäner zu Frauen betrug 4,7 : 1. Morphologisch fanden sich „klassische“ DFSP (25/34; 73,5 %), pigmentierte DFSP (2/34; 5,9 %), DFSP mit myoider Differenzierung (1/34; 2,9 %) und fibrosarkomatös transformierte DFSP (DFSP‐FS) (6/34; 17,6 %). Zusätzlich zeigte sich bei drei Fällen mit DFSP‐FS eine myxoide Degeneration (3/6; 50,0 %). In allen 29 Fällen mit CD34‐Immunhistochemie‐Untersuchung fand sich eine positive Anfärbung (100 %). In der genetischen Untersuchung wiesen 94,1 % (16/17) der Patienten eine PDGFB‐Rearrangement/COL1A1‐PDGFB‐Fusion auf. Die Raten an Rezidiven (83,3 % vs. 59,1 %) und Metastasierung (33,3 % vs. 0) lagen bei den DFSP‐FS deutlich höher als bei den gewöhnlichen DFSP. In allen Fällen von Rezidiven waren die Schnittränder vorher als positiv eingestuft worden. Umgekehrt waren alle Patienten mit negativen Schnitträndern (bei der Exzision oder Re‐Exzision) noch am Leben, ohne weitere Krankheitszeichen aufzuweisen (Mittel 81,8 Monate, Median 81 Monate).

Schlussfolgerung

DFSP tritt vor allem bei Männern auf. Bei DFSP‐FS besteht eine höhere Wahrscheinlichkeit für myxoide Degeneration bei insgesamt schlechterer Prognose. Ein negativer Status der chirurgischen Schnittränder zeigte eine gute Prognose an.
Klinisch‐pathologische Merkmale und histologische Tumorreste in Reexzisionspräparaten unvollständig resezierter Basalzellkarzinome
Authors: Lütgerath Constantin , Weiß Christel , Böer‐Auer Almut
Published: November 2022

Hintergrund und Zielsetzung

Die chirurgische Exzision ist die bedeutendste Therapiemodalität zur Versorgung von Basalzellkarzinomen (BCC). Oft kommt es zu einer unvollständigen Exzision, die eine Reexzision nach sich zieht. Allerdings enthalten Reexzisionspräparate häufig keine Tumorreste, weswegen die Reexzision im Nachhinein überflüssig ist. Ziel unserer Studie ist die Identifikation von klinisch‐pathologischen Merkmalen, die mit dem Vorhandensein von histologischen Tumorresten in Reexzisionspräparaten assoziiert sind.

Patienten und Methoden

255 unvollständig resezierte BCC von 222 Patienten wurden in diese Fall‐Kontroll‐Beobachtungsstudie eingeschlossen. Acht klinisch‐pathologische Merkmale wurden in einer binären logistischen Regressionsanalyse mit dem Vorhandensein oder Nichtvorhandensein von histologischen Tumorresten in Reexzisionspräparaten korreliert.

Ergebnisse

Ein höheres Alter bei der ersten Exzision und ein BCC in der Rezidiv‐Hochrisikozone erwiesen sich als unabhängige Risikofaktoren für das Vorhandensein von histologischen Tumorresten in Reexzisionspräparaten.

Schlussfolgerungen

Die Ergebnisse unserer Studie zeigen, dass eine Reexzision von unvollständig resezierten BCC in der oben genannten Subpopulation definitiv notwendig ist. Für die Nachbehandlung unvollständig resezierter BCC, die sich in der Rezidiv‐Niedrigrisikozone jüngerer Patienten befinden, können jedoch auch weniger invasive Therapien wie Imiquimod in Betracht gezogen werden.
Patientenpräferenzen bei Hidradenitis suppurativa (APProach‐HS): ein “Discrete‐Choice”‐Experiment
Authors: Faverio Kristin , Peitsch Wiebke K. , Görig Tatiana , Schneider‐Burrus Sylke , Benzel Friderike , Goebeler Matthias , Schummer Patrick , Badran Alaa , Schaarschmidt Marthe‐Lisa , Harth Wolfgang , Mössner Rotraut , Kromer Christian
Published: November 2022

Hintergrund und Zielsetzungen

Die Behandlungsoptionen für mittelschwere bis schwere Hidradenitis suppurativa (HS) umfassen Antibiotika, Biologika und verschiedene chirurgische Verfahren. Diese Ansätze unterscheiden sich stark bezüglich des Behandlungsprozesses, der Erfolgsraten und der unerwünschten Ereignisse. Informationen zu den Präferenzen der Patienten in Bezug auf HS‐Therapien gibt es aktuell nur wenige. Unser Ziel war es, Patientenpräferenzen für die medikamentöse und chirurgische Behandlung der HS durch Conjoint‐Analyse zu untersuchen.

Patienten und Methoden

In dieser Querschnittsstudie wurden durch computergestützte „Discrete‐Choice“ Experimente die Präferenzen der Patienten für HS‐Therapien quantifiziert, und zwar aufgeschlüsselt nach Behandlungsmodalität (Tabletten, subkutane Injektionen, chirurgische Eingriffe mit sekundärer Heilungsabsicht oder primärer Verschluss), Wahrscheinlichkeit eines anhaltenden Therapieerfolgs, Wahrscheinlichkeit leichter oder schwerer unerwünschter Ereignisse und Dauer der Behandlung oder Wundheilung.

Ergebnisse

Gemittelt über die Kohorte (n = 216 Patienten mit HS) wurde der anhaltende Therapieerfolg als am wichtigsten angesehen (Relative Importance Score [RIS]: 36,2), gefolgt von der Behandlungsmodalität (RIS: 24,0) und der Dauer der Behandlung/Wundheilung (RIS: 19,9), während leichte oder schwere unerwünschte Ereignisse (RIS: 10,7 beziehungsweise 9,3) als weniger wichtig angesehen wurden. Die Patienten bevorzugten Tabletten gegenüber subkutanen Injektionen und lehnten eine Operation mit primärem Verschluss ab. Die Präferenzen unterschieden sich deutlich je nach Alter und den betroffenen Körperregionen.

Schlussfolgerung

Die Kenntnis der Patientenpräferenzen ist für eine patientenzentrierte Versorgung bei HS von wesentlicher Bedeutung.
Health, education, and social care provision after diagnosis of childhood visual disability
Authors: Solebo Ameenat Lola , Teoh Lucinda Jade , Sargent Jenefer , Rahi Jugnoo Sangeeta ,   British Childhood Visual Impairment and Blindness Study Interest Group
Published: November 2022

Aim

To investigate the health, education, and social care provision for children newly diagnosed with visual disability.

Method

This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vision. Data collection was performed by managing clinicians up to 1‐year follow‐up, and included health and developmental needs, and health, education, and social care provision.

Results

BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two‐thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2 p < 0.001), or had an EHCP (11% vs 7%, χ2 p < 0.01).

Interpretation

Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.

What this paper adds

One year after visual disability diagnosis, one in three children had not received the recommended care from a multidisciplinary team.

Two‐thirds had not yet received the recommended Education, Health, and Care Plan.

There is an under‐provision of recommended care, despite significant and complex need.
Virtual screening and in vitro experiments highlight cannabidiol as a drug‐like phosphodiesterase 9 inhibitor
Authors: Ribaudo Giovanni , Landucci Elisa , Giannangeli Matteo , Mazzantini Costanza , Maccarinelli Giuseppina , Mastinu Andrea , Bonini Sara Anna , Memo Maurizio , Pellegrini‐Giampietro Domenico E. , Gianoncelli Alessandra
Published: November 2022

The growing interest on the therapeutic potential against neurodegeneration of Cannabis sativa extracts, and of phytocannabinoids in particular, is paralleled by a limited understanding of the undergoing biochemical pathways in which these natural compounds may be involved. Computational tools are nowadays commonly enrolled in the drug discovery workflow and can guide the investigation of macromolecular targets for such molecules. In this contribution, in silico techniques have been applied to the study of C. sativa constituents at various extents, and a total of seven phytocannabinoids and four terpenes were considered. On the side of ligand‐based virtual screening, physico‐chemical descriptors were computed and evaluated, highlighting the phytocannabinoids possessing suitable drug‐like properties to potentially target the central nervous system. Our previous findings and literature data prompted us to investigate the interaction of these molecules with phosphodiesterases (PDEs), a family of enzymes being studied for the development of therapeutic agents against neurodegeneration. Among the compounds, structure‐based techniques such as docking and molecular dynamics (MD), highlighted cannabidiol (CBD) as a potential and selective PDE9 ligand, since a promising calculated binding energy value (−9.1 kcal/mol) and a stable interaction in the MD simulation timeframe were predicted.

Additionally, PDE9 inhibition assay confirmed the computational results, and showed that CBD inhibits the enzyme in the nanomolar range in vitro, paving the way for further development of this phytocannabinoid as a therapeutic option against neurodegeneration.
Continuous straw return for 8 years mitigates the negative effects of inorganic fertilisers on C‐cycling soil bacteria
Authors: Zhang Qian , Guo Tengfei , Sheng Kai , Shi Wenxuan , Han Yanlai , Wang Yilun , Li Hui
Published: November 2022

To elucidate the identity and mechanisms by which specific bacterial members drive efficient decomposition and utilisation of straw, the succession and co‐occurrence patterns of 13C‐labelled bacteria were analysed using DNA‐stable isotope probing (SIP) techniques. Microcosms with 13C‐labelled maize straw incorporated into soils subjected to no nitrogen (N) fertiliser (CK), chemical fertiliser (NPK) and chemical fertiliser with straw return (NPKS) treatments for 8 years were incubated for 360 days. The results showed that fertilisation regimes changed the 13C‐labelled bacterial groups by abundance but not taxonomic composition, where N fertiliser application (NPK and NPKS treatments) reduced the relative abundance of maize straw carbon assimilators affiliated with Arthrobacter, Sphingomonas, Streptomyces, Burkholderia‐Caballeronia‐Paraburkholderia and Kribbella, but increased the relative abundance of Nocardioides, Rhodanobacter, Granulicella and Chujaibacter. Compared with CK and NPKS‐treated soils, continuous inorganic fertilisation reduced the α‐diversity of the 13C‐labelled bacterial community and resulted in a loose and less competitive co‐occurrence network of straw C‐assimilators with more hubs needed to sustain its structural stability. Interestingly, straw return mitigated the negative effects of inorganic fertilisation by forming a tight and complex co‐occurrence network of maize straw utilizers associated with NPKS‐treated soils. Taken together, we emphasise the vital function of long‐term straw return for sustaining soil biodiversity under intensive fertilised agricultural conditions and provide reference bacterial members for efficient straw utilisation.

Highlights

DNA‐SIP enabled the concise identification of straw C assimilating bacterial members.

Inorganic fertilisation reduced straw C‐utilizer community diversity and their interactions.

Straw return mitigates the negative effects of inorganic fertilisers on straw C‐cycling bacteria.

Varying taxa sustained the interaction network of straw C‐utilizers in different fertilised soils.