bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted deletion of keratin 8 in intestinal epithelial cells disrupts tissue integrity and predisposes to tumorigenesis in the colon
Authors: Stenvall Carl-Gustaf A. , Tayyab Mina , Grönroos Tove J. , Ilomäki Maria A. , Viiri Keijo , Ridge Karen M. , Polari Lauri , Toivola Diana M. 
Published: December 2021

AbstractKeratin 8 (K8) is the main intestinal epithelial intermediate filament protein with proposed roles for colonic epithelial cell integrity. Here, we used mice lacking K8 in intestinal epithelial cells (floxed K8 and Villin-Cre1000 and Villin-CreERt2) to investigate the cell-specific roles of intestinal epithelial K8 for colonocyte function and pathologies. Intestinal epithelial K8 deletion decreased K8 partner proteins, K18–K20, 75–95%, and the remaining keratin filaments were located at the colonocyte apical regions with type II K7, which decreased 30%. 2-Deoxy-2-[18F]-fluoroglucose positron emission tomography in vivo imaging identified a metabolic phenotype in the lower gut of the conditional K8 knockouts. These mice developed intestinal barrier leakiness, mild diarrhea, and epithelial damage, especially in the proximal colon. Mice exhibited shifted differentiation from enterocytes to goblet cells, displayed longer crypts and an increased number of Ki67 + transit-amplifying cells in the colon. Significant proproliferative and regenerative signaling occurred in the IL-22, STAT3, and pRb pathways, with minor effects on inflammatory parameters, which, however, increased in aging mice. Importantly, colonocyte K8 deletion induced a dramatically increased sensitivity to azoxymethane-induced tumorigenesis. In conclusion, intestinal epithelial K8 plays a significant role in colonocyte epithelial integrity maintenance, proliferation regulation and tumor suppression.
Graphical abstract
A minimally invasive cerclage of the tibia in a modified Goetze technique: operative technique and first clinical results
Authors: Förch Stefan , Reuter Jan , von der Helm Franziska , Lisitano Leonard , Hartwig Christopher , Sandriesser Sabrina , Nuber Stefan , Mayr Edgar 
Published: December 2021

Abstract
Introduction
In spiral fractures of the tibia, the stability of an osteosynthesis may be significantly increased by additive cerclages and, according to biomechanical studies, be brought into a state that allows immediate full weight bearing. As early as 1933, Goetze described a minimally invasive technique for classic steel cerclages. This technique was modified, so that it can be used for modern cable cerclages in a soft part saving way.

Method
After closed reduction, an 8 Fr redon drain is first inserted in a minimally invasive manner, strictly along the bone and placed around the tibia via 1 cm incisions on the anterolateral and dorsomedial tibial edges using a curette and a tissue protection sleeve.
Via this drain, a 1.7 mm cable cerclage can be inserted. The fracture is then anatomically reduced while simultaneously tightening the cerclage. Subsequently, a nail or a minimally invasive plate osteosynthesis is executed using the standard technique.
Using the hospital documentation system, data of patients that were treated with additional cerclages for tibial fractures between 01/01/2014 and 06/30/2020 were subjected to a retrospective analysis for postoperative complications (wound-healing problems, infections and neurovascular injury). Inclusion criteria were: operatively treated tibial fractures, at least one minimally invasive additive cerclage, and age of 18 years or older. Exclusion criteria were: periprosthetic or pathological fractures and the primary need of reconstructive plastic surgery. SPSS was used for statistical analysis.

Results
96 tibial shaft spiral fractures were treated with a total of 113 additive cerclages. The foregoing resulted in 10 (10.4%) postoperative wound infections, 7 of which did not involve the cerclage. One lesion of the profundal peroneal nerve was detected, which largely declined after cerclage removal. In 3 cases, local irritation from the cerclage occurred and required removal of material.

Conclusion
In the described technique, cerclages may be inserted additively at the tibia in a minimally invasive manner and with a few complications, thus significantly increasing the stability of an osteosynthesis. How this ultimately affects fracture healing is the subject of an ongoing study.
Trends in inpatient care for psychiatric disorders in NHS hospitals across England, 1998/99–2019/20: an observational time series analysis
Authors: Degli Esposti Michelle , Ziauddeen Hisham , Bowes Lucy , Reeves Aaron , Chekroud Adam M. , Humphreys David K. , Ford Tamsin 
Published: December 2021

Abstract
Purpose
It is unclear how hospitals are responding to the mental health needs of the population in England, against a backdrop of diminishing resources. We aimed to document patterns in hospital activity by psychiatric disorder and how these have changed over the last 22 years.

Methods
In this observational time series analysis, we used routinely collected data on all NHS hospitals in England from 1998/99 to 2019/20. Trends in hospital admissions and bed days for psychiatric disorders were smoothed using negative binomial regression models with year as the exposure and rates (per 1000 person-years) as the outcome. When linear trends were not appropriate, we fitted segmented negative binomial regression models with one change-point. We stratified by gender and age group [children (0–14 years); adults (15 years +)].

Results
Hospital admission rates and bed days for all psychiatric disorders decreased by 28.4 and 38.3%, respectively. Trends were not uniform across psychiatric disorders or age groups. Admission rates mainly decreased over time, except for anxiety and eating disorders which doubled over the 22-year period, significantly increasing by 2.9% (AAPC = 2.88; 95% CI: 2.61–3.16; p < 0.001) and 3.4% (AAPC = 3.44; 95% CI: 3.04–3.85; p < 0.001) each year. Inpatient hospital activity among children showed more increasing and pronounced trends than adults, including an increase of 212.9% for depression, despite a 63.8% reduction for adults with depression during the same period.

Conclusion
In the last 22 years, there have been overall reductions in hospital activity for psychiatric disorders. However, some disorders showed pronounced increases, pointing to areas of growing need for inpatient psychiatric care, especially among children.
QCM-based assay designs for human serum albumin
Authors: Sudjarwo Wisnu Arfian A. , Dobler Mathias Thomas , Lieberzeit Peter A. 
Published: December 2021

AbstractSolid-phase synthesis is an elegant way to create molecularly imprinted polymer nanoparticles (nano-MIPs) comprising a single binding site, i.e. mimics of antibodies. When using human serum albumin (HSA) as the template, one achieves nano-MIPs with 53 ± 19 nm diameter, while non-imprinted polymer nanoparticles (nano-NIPs) reach 191 ± 96 nm. Fluorescence assays lead to Stern–Volmer plots revealing selective binding to HSA with selectivity factors of 1.2 compared to bovine serum albumin (BSA), 1.9 for lysozyme, and 4.1 for pepsin. Direct quartz crystal microbalance (QCM) assays confirm these results: nano-MIPs bind to HSA immobilized on QCM surfaces. This opens the way for competitive QCM-based assays for HSA: adding HSA to nanoparticle solutions indeed reduces binding to the QCM surfaces in a concentration-dependent manner. They achieve a limit of detection (LoD) of 80 nM and a limit of quantification (LoQ) of 244 nM. Furthermore, the assay shows recovery rates around 100% for HSA even in the presence of competing analytes.
A cross-scanner and cross-tracer deep learning method for the recovery of standard-dose imaging quality from low-dose PET
Authors: Xue Song , Guo Rui , Bohn Karl Peter , Matzke Jared , Viscione Marco , Alberts Ian , Meng Hongping , Sun Chenwei , Zhang Miao , Zhang Min , Sznitman Raphael , El Fakhri Georges , Rominger Axel , Li Biao , Shi Kuangyu 
Published: December 2021

Abstract

Purpose
A critical bottleneck for the credibility of artificial intelligence (AI) is replicating the results in the diversity of clinical practice. We aimed to develop an AI that can be independently applied to recover high-quality imaging from low-dose scans on different scanners and tracers.

Methods
Brain [18F]FDG PET imaging of 237 patients scanned with one scanner was used for the development of AI technology. The developed algorithm was then tested on [18F]FDG PET images of 45 patients scanned with three different scanners, [18F]FET PET images of 18 patients scanned with two different scanners, as well as [18F]Florbetapir images of 10 patients. A conditional generative adversarial network (GAN) was customized for cross-scanner and cross-tracer optimization. Three nuclear medicine physicians independently assessed the utility of the results in a clinical setting.

Results
The improvement achieved by AI recovery significantly correlated with the baseline image quality indicated by structural similarity index measurement (SSIM) (r = −0.71, p < 0.05) and normalized dose acquisition (r = −0.60, p < 0.05). Our cross-scanner and cross-tracer AI methodology showed utility based on both physical and clinical image assessment (p < 0.05).

Conclusion
The deep learning development for extensible application on unknown scanners and tracers may improve the trustworthiness and clinical acceptability of AI-based dose reduction.
[177Lu]Lu-DOTA-TATE versus standard of care in adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs): a cost-consequence analysis from an Italian hospital perspective
Authors: Spada Francesca , Campana Davide , Lamberti Giuseppe , Laudicella Riccardo , Dellamano Renato , Dellamano Luca , Leeuwenkamp Oscar , Baldari Sergio 
Published: December 2021

Abstract
Purpose
To assess and compare clinical outcomes and costs, to the Italian healthcare system, of three therapeutic options approved in the management of adult patients with gastro-enteropancreatic neuroendocrine tumours (GEP-NETs).

Methods
We compared the efficacy, safety, and costs of [177Lu]Lu-DOTA-TATE, everolimus (both originator and generic products), and sunitinib in patients with advanced GEP-NETs (NET G1 and G2) that had progressed following treatment with somatostatin analogs (SSAs). A cost-consequence model was developed and validated by a panel of clinical experts from three NET reference centres in Italy. The clinical outcomes included in the model were median progression-free survival and the incidence of grade 3 or 4 adverse events (AEs), as reported in pivotal clinical trials. The costs for acquisition and administration of each treatment, and of managing AEs, were calculated from the perspective of the Italian national health service. Treatment costs per progression-free month were calculated separately for patients with NETs of pancreatic (PanNETs; all three treatments) and gastrointestinal (GI-NETs; [177Lu]Lu-DOTA-TATE and everolimus only) origin.

Results
In patients with PanNETs, total costs per progression-free month were €2989 for [177Lu]Lu-DOTA-TATE, €4975 for originator everolimus, €3472 for generic everolimus, and €5337 for sunitinib. In patients with GI-NETs, total costs per progression-free month were €3189 for [177Lu]Lu-DOTA-TATE, €4990 for originator everolimus, and €3483 for generic everolimus.

Conclusions
[177Lu]Lu-DOTA-TATE was associated with lower costs per progression-free month versus relevant treatment options in patients with GI-NETs or PanNETs (NET G1–G2; progressed following SSA treatment), although acquisition and administration costs are higher. These findings provide further economic arguments in the overall context of treatment decision-making.
Impact of oral lipid and glucose tolerance tests on the postprandial concentrations of angiopoietin-like proteins (Angptl) 3 and 4
Authors: Schmid Andreas , Belikan Hannah , Höpfinger Alexandra , Schäffler Andreas , Karrasch Thomas 
Published: December 2021

Abstract
Background
The postprandial regulation of angiopoietin-like proteins (Angptls) and their expression in adipocytes is poorly characterized.

Objective
Circulating Angptl3 and 4 were analyzed in healthy individuals undergoing either an oral lipid tolerance test (OLTT; n = 98) or an oral glucose tolerance test (OGTT; n = 99). Venous blood was drawn after 0, 2, 4, and 6 h during OLTT and after 0, 1, and 2 h during OGTT. Anthropometric and laboratory parameters were assessed and concentrations of Angptls were quantified by enzyme-linked immunosorbent assay. Angptl gene expression in 3T3-L1 adipocytes and in murine adipose tissues and cellular fractions was analyzed by quantitative real-time PCR.

Results
Angptl3 concentrations significantly decreased while Angptl4 levels continuously increased during OLTT. Both proteins remained unaffected during OGTT. Angptl3 and Angptl4 were expressed in murine subcutaneous and visceral AT with higher mRNA levels in mature adipocytes when compared to the stroma-vascular cell fraction. Both proteins were strongly induced during 3T3-L1 adipocyte differentiation and they were unresponsive to glucose in mature fat cells. Adipocyte Angptl3 (but not Angptl4) mRNA expression was inhibited by the polyunsaturated fatty acids arachidonic acid and docosahexaenoic acid, whereas nine types of dietary fatty acids remained without any effect.

Conclusions
There is evidence of short-time regulation of Angptl3/4 levels upon metabolic stress. Angptl4 expression is high and Angptl3 expression is low in AT and restricted mainly to mature adipocytes without any differences concerning fat compartments. Whereas dietary fatty acids and glucose are without any effect, omega-3/-6-polyunsaturated fatty acids inhibited Anptl3 expression in adipocytes.
Seeking Horses: Allies, Clients and Exchanges in the Zhou Period (1045–221 BC)
Authors: Rawson Jessica , Huan Limin , Taylor William Timothy Treal 
Published: December 2021

AbstractHorses and chariots—and the associated technology and expertise—derived from the steppe contributed to the success of the Zhou conquest of the Shang in c. 1045 BC and remained important throughout Zhou rule in ancient China. On the basis of material cultural patterns, including the style and material used in bridle cheek-pieces found in tombs of the late second and early first millennium BC, this paper points to a northern origin for Zhou horses. Important intermediaries, providing these horses, were the clans whose cemeteries have been identified on the northern edges of the Central Plains. The necessity for repeated exchanges bringing south horses from the north was a consequence of key environmental differences between the steppe and the Central Plains, including climate, geomorphology, essential soil nutrients, and land use. These created significant difficulties in sustainably breeding and pasturing horses of quality. As a result, the people of the Central Plains were bound, over millennia, to seek horses from the northwest, along a cultural corridor that also moved northern materials and technologies, such as gold-, iron- and some bronze-working, into the Central Plains from the steppes.
Identification of key gene networks controlling vernalization development characteristics of Isatis indigotica by full-length transcriptomes and gene expression profiles
Authors: Wang Pan , Liu Dong , Yang Fu-Hong , Ge Hui , Zhao Xin , Chen Hong-Gang , Du Tao 
Published: December 2021

AbstractIsatis indigotica Fort., as a common Chinese medicinal raw material, will lose its medicinal value if it blooms early, so it is highly valuable to clarify the induction mechanism of the vernalization of I. indigotica at low temperature. In this study, the concentrations of soluble sugar, proline, glutathione and zeatin in two germplasms of I. indigotica with different degrees of low temperature tolerance (Y1 and Y2) were determined at 10 days, 20 days and 30 days of low-temperature treatment, and the full-length transcriptome of 24 samples was sequenced by Nanopore sequencing with Oxford Nanopore Technologies (ONT). After that, the data of transcripts involved in the vernalization of I. indigotica at low temperature were obtained, and these transcripts were identified using weighted gene co-expression network analysis (WGCNA). The results revealed the massive accumulation of soluble sugar and proline in Y1 and Y2 after low temperature induction. A total of 18,385 new transcripts, 6168 transcription factors and 470 lncRNAs were obtained. Differential expression analysis showed that gibberellin, flavonoids, fatty acids and some processes related to low temperature response were significantly enriched. Eight key transcripts were identified by WGCNA, among which ONT.14640.1, ONT.9119.1, ONT.13080.2 and ONT.16007.1 encodes a flavonoid transporter, 9-cis-epoxycarotenoid dioxygenase 3 (NCED3), growth factor gene and L-aspartate oxidase in plants, respectively. It indicated that secondary metabolites such as hormones and flavonoids play an important role in the vernalization of I. indigotica. qRT-PCR proved the reliability of transcriptome results. These results provide important insights on the low-temperature vernalization of I. indigotica, and provide a research basis for analyzing the vernalization mechanism of I. indigotica.
Defect engineering of BCZT-based piezoelectric ceramics with high piezoelectric properties
Authors: Wang Xinjian , Huan Yu , Zhu Yixuan , Zhang Peng , Yang Wenlong , Li Peng , Wei Tao , Li Longtu , Wang Xiaohui 
Published: December 2021

AbstractThe intrinsic conduction mechanism and optimal sintering atmosphere of (Ba0.85Ca0.15)(Zr0.1Ti0.9)O3 (BCZT) ceramics were regulated by Mn-doping element in this work. By Hall and impedance analysis, the undoped BCZT ceramics exhibit a typical n-type conduction mechanism, and the electron concentration decreases with the increasing oxygen partial pressure. Therefore, the undoped ceramics exhibit best electrical properties (piezoelectrical constant d33 = 585 pC·N−1, electro-mechanical coupling factor kp = 56%) in O2. A handful of Mn-doping element would transfer the conduction mechanism from n-type into p-type. And the hole concentration reduces with the decreasing oxygen partial pressure for Mn-doped BCZT ceramics. Therefore, the Mn-doped ceramics sintered in N2 have the highest insulation resistance and best piezoelectric properties (d33 = 505 pC·N−1, kp = 50%). The experimental results demonstrate that the Mn-doping element can effectively adjust the intrinsic conduction mechanism and then predict the optimal atmosphere.
Effect of Vaginal Stretching and Photobiomodulation Therapy on Sexual Function in Women with Pelvic Floor Myofascial Pain - A Randomized Clinical Trial
Authors: Frederice Claudia Pignatti , de Mira Ticiana Aparecida Alves , Machado Helymar Costa , Brito Luiz Gustavo Oliveira , Juliato Cássia R.T. 
Published: December 2021

ABSTRACTBackgroundSpasm or increased tonus of the pelvic floor muscles (PFM) can cause myofascial pain (MP), which may result in painful intercourse and sexual dysfunction.AimThe effect of vaginal stretching (VS) with photobiomodulation therapy (PBMT) is compared to VS with sham PBMT in overall sexual function, rate and severity of painful intercourse at baseline and after treatment in women with pelvic floor MP.MethodsA double-blind randomized clinical trial of 103 women with MP: 1 group received 10 sessions of VS with PBMT (4 Joules of near-infrared light-808 nm at 3 points), and the other group received VS with sham PBMT.OutcomesImpact of treatment was measured by the number of women experiencing painful intercourse, Pain severity was measured by Visual Analog Scale and sexual function was assessed by the FSFI questionnaire. Variables were assessed at baseline and after ten sessions in the intervention groups.ResultsAfter treatment, the number of women experiencing painful intercourse was significantly lower in both the VS with PBMT group (90.2–55%, P = .001), and VS with sham PBMT group (86.6–46.2%, P &lt; .001). There was a significant reduction in pain measure by Visual Analog Scale (P &lt; .001, [VS with PBMT group: P = .002; VS with sham PBMT group: P &lt; .001]). There was a significant decrease in the number of participants with sexual dysfunction (FSFI score ≤26.55) after the treatment in the VS with PBMT group (92.2–74.5%, P = .003) and in the VS with sham PBMT group (90.4–76.9%, P = .035). Both groups showed improvement in the FSFI pain domain after treatment (P &lt; .001, [VS with PBMT group: P = .038; VS with sham PBMT group: P = .005]). Only the VS with sham PBMT group had a significant increase in FSFI desire and total score (P &lt; .001) after treatment.Clinical ImplicationsWe found that VS associated or not with PBMT may be effective in reducing complaints of painful intercourse, alleviating pain severity, and reducing the number of women with pelvic floor MP suffering from sexual dysfunction.Strengths & LimitationsStrengths of this study are the randomized design and use of validated questionnaires. Limitation of the study is the lack of a long follow-up period and the lack of a usual care comparison group hampers generalizability of the results.ConclusionVS only and VS with PBMT have short-term efficacy in reducing painful intercourse and reducing a number of women with sexual dysfunction.
The Aura of Confucius
Authors: Murray Julia K. 
Published: December 2021

The Aura of Confucius is a ground-breaking study that reconstructs the remarkable history of Kongzhai, a shrine founded on the belief that Confucius' descendants buried the sage's robe and cap a millennium after his death and far from his home in Qufu, Shandong. Improbably located on the outskirts of modern Shanghai, Kongzhai featured architecture, visual images, and physical artifacts that created a 'Little Queli,' a surrogate for the temple, cemetery, and Kong descendants' mansion in Qufu. Centered on the Tomb of the Robe and Cap, with a Sage Hall noteworthy for displaying sculptural icons and not just inscribed tablets, Kongzhai attracted scholarly pilgrims who came to experience Confucius's beneficent aura. Although Kongzhai gained recognition from the Kangxi emperor, its fortunes declined with modernization, and it was finally destroyed during the Cultural Revolution. Unlike other sites, Kongzhai has not been rebuilt and its history is officially forgotten, despite the Confucian revival in contemporary China.
Purity and Pollution in the Hebrew Bible
Authors: Feder Yitzhaq 
Published: December 2021

In this book, Yitzhaq Feder presents a novel and compelling account of pollution in ancient Israel, from its emergence as an embodied concept, rooted in physiological experience, to its expression as a pervasive metaphor in social-moral discourse. Feder aims to bring the biblical and ancient Near Eastern evidence into a sustained conversation with anthropological and psychological research through comparison with notions of contagion in other ancient and modern cultural contexts. Showing how numerous interpretive difficulties are the result of imposing modern concepts on the ancient texts, he guides readers through wide-ranging parallels to biblical attitudes in ancient Near Eastern, ethnographic, and modern cultures. Feder demonstrates how contemporary evolutionary and psychological research can be applied to ancient textual evidence. He also suggests a path of synthesis that can move beyond the polarized positions which currently characterize modern academic and popular debates bearing on the roles of biology and culture in shaping human behavior.