bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wheat Sourdough Breadmaking: A Scoping Review
Authors: De Bondt Yamina , Verdonck Celine , Brandt Markus J. , De Vuyst Luc , Gänzle Michael G. , Gobbetti Marco , Zannini Emanuele , Courtin Christophe M. 
Published: January 2024

Using sourdough in breadmaking can enhance bread's shelf-life and flavor compared to exclusive baker's yeast use and is believed to increase its nutritional quality and healthiness. Previous research established insight into the microbial ecology of sourdough, but the link between leavening agent use, processing, and bread quality remains elusive. However, such knowledge is key for standardization, research on the health benefits, and the definition of sourdough bread. In this systematic scoping review, we analyzed 253 studies and identified large variations in the type and amount of leavening agent, fermentation conditions, and bread quality (specific loaf volume and acidification). The interrelation between these elements and their effect on the extent of fermentation is discussed, together with issues preventing proper comparison of breadmaking procedures. With this review, we want to contribute to the dialogue concerning the definition of sourdough-type bread products and the research into the health benefits attributed to them.
Subclonal Cancer Driver Mutations Are Prevalent in the Unresected Peritumoral Edema of Adult Diffuse Gliomas
Authors: Underhill Hunter R. , Karsy Michael , Davidson Christian J. , Hellwig Sabine , Stevenson Samuel , Goold Eric A. , Vincenti Sydney , Sellers Drew L. , Dean Charlie , Harrison Brion E. , Bronner Mary P. , Colman Howard , Jensen Randy L. 
Published: January 2024

Abstract

Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, unresected region could provide important insights into residual disease. A key obstacle has been the inability to distinguish between next-generation sequencing (NGS) noise and the true but weak signal from tumor cells hidden among the noncancerous brain tissue of the peritumoral edema. Here, we developed and validated True2 sequencing to reduce NGS-associated errors to &lt;1 false positive/100 kb panel positions while detecting 97.6% of somatic mutations with an allele frequency ≥0.1%. True2 was then used to study the tumor and peritumoral edema of 22 adult diffuse gliomas including glioblastoma, astrocytoma, oligodendroglioma, and NF1-related low-grade neuroglioma. The tumor and peritumoral edema displayed a similar mutation burden, indicating that surgery debulks these cancers physically but not molecularly. Moreover, variants in the peritumoral edema included unique cancer driver mutations absent in the bulk tumor. Finally, analysis of multiple samples from each patient revealed multiple subclones with unique mutations in the same gene in 17 of 22 patients, supporting the occurrence of convergent evolution in response to patient-specific selective pressures in the tumor microenvironment that may form the molecular foundation of recurrent disease. Collectively, True2 enables the detection of ultralow frequency mutations during molecular analyses of adult diffuse gliomas, which is necessary to understand cancer evolution, recurrence, and individual response to therapy.

Significance:
True2 is a next-generation sequencing workflow that facilitates unbiased discovery of somatic mutations across the full range of variant allele frequencies, which could help identify residual disease vulnerabilities for targeted adjuvant therapies.
Risk of Clinically Significant Prostate Cancer after a Nonsuspicious Prostate MRI—A Comparison with the General Population
Authors: Pylväläinen Juho , Hoffström Jaakko , Kenttämies Anu , Auvinen Anssi , Mirtti Tuomas , Rannikko Antti 
Published: January 2024

Abstract

Background:
We compare the risk of clinically significant (csPCa; ISUP Grade Group ≥ 2) and insignificant prostate cancer (isPCa; ISUP Grade Group 1) in men with a nonsuspicious prostate MRI (nMRI; PI-RADS ≤ 2) with the general population, and assess the value of PSA density (PSAD) in stratification.

Methods:
In this retrospective population-based cohort study we identified 1,682 50–79-year-old men, who underwent nMRI at HUS (2016–2019). We compared their age-standardized incidence rates (IR) of csPCa and the odds of isPCa to a local age- and sex-matched general population (n = 230,458) during a six-year follow-up. Comparisons were performed by calculating incidence rate ratios (IRR) and ORs with 95% confidence intervals (CI). We repeated the comparison for the 920 men with nMRI and PSAD &lt; 0.15 ng/mL/cm3.

Results:
Compared with the general population, the IR of csPCa was significantly higher after nMRI [1,852 vs. 552 per 100,000 person-years; IRR 3.4 (95% CI, 2.8–4.1)]. However, the IR was substantially lower if PSAD was low [778 per 100,000 person-years; IRR 1.4 (95% CI, 0.9–2.0)]. ORs for isPCa were 2.4 (95% CI, 1.7–3.5) for all men with nMRI and 5.0 (95% CI, 2.8–9.1) if PSAD was low.

Conclusions:
Compared with the general population, the risk of csPCa is not negligible after nMRI. However, men with nMRI and PSAD &lt;0.15 ng/mL/cm3 have worse harm-benefit balance than men in the general population.

Impact:
Prostate biopsies for men with nMRI should be reserved for cases indicated by additional risk stratification.
See related In the Spotlight, p. 641
The Associations between Intakes of One-Carbon Metabolism–Related Vitamins and Breast Density among Young Women
Authors: Han Eunyoung , Van Horn Linda , Snetselaar Linda , Shepherd John A. , Park Yoon Jung , Kim Hyesook , Jung Seungyoun , Dorgan Joanne F. 
Published: January 2024

Abstract

Background:
Folate is the primary methyl donor and B vitamins are cofactors for one-carbon metabolism that maintain DNA integrity and epigenetic signatures implicated in carcinogenesis. Breast tissue is particularly susceptible to stimuli in early life. Only limited data are available on associations of one-carbon metabolism–related vitamin intake during youth and young adulthood with breast density, a strong risk factor for breast cancer.

Methods:
Over 18 years in the DISC and DISC06 Follow-up Study, diets of 182 young women were assessed by three 24-hour recalls on five occasions at ages 8 to 18 years and once at 25 to 29 years. Multivariable-adjusted linear mixed-effects regression was used to examine associations of intakes of one-carbon metabolism-related vitamins with MRI-measured percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) at ages 25 to 29 years.

Results:
Folate intake in youth was inversely associated with %DBV (Ptrend = 0.006) and ADBV (Ptrend = 0.02). These inverse associations were observed with intake during post-, though not premenarche. In contrast, premenarche vitamin B2 intake was positively associated with ADBV (Ptrend &lt; 0.001). Young adult folate and vitamin B6 intakes were inversely associated with %DBV (all Ptrend ≤ 0.04), whereas vitamins B6 and B12 were inversely associated with ADBV (all Ptrend ≤ 0.04).

Conclusions:
Among these DISC participants intakes of one-carbon metabolism-related vitamins were associated with breast density. Larger prospective studies among diverse populations are needed to replicate these findings.

Impact:
Our results suggest the importance of one-carbon metabolism-related vitamin intakes early in life with development of breast density and thereby potentially breast cancer risk later in life.
Dual-Hit Strategy for Therapeutic Targeting of Pancreatic Cancer in Patient-Derived Xenograft Tumors
Authors: Roy Chaudhuri Tista , Lin Qingxiang , Stachowiak Ewa K. , Rosario Spencer R. , Spernyak Joseph A. , Ma Wen Wee , Stachowiak Michal K. , Greene Michelle K. , Quinn Gerard P. , McDade Simon S. , Clynes Martin , Scott Christopher J. , Straubinger Robert M. 
Published: January 2024

Abstract

Purpose:
Paracrine activation of pro-fibrotic hedgehog (HH) signaling in pancreatic ductal adenocarcinoma (PDAC) results in stromal amplification that compromises tumor drug delivery, efficacy, and patient survival. Interdiction of HH-mediated tumor-stroma crosstalk with smoothened (SMO) inhibitors (SHHi) “primes” PDAC patient-derived xenograft (PDX) tumors for increased drug delivery by transiently increasing vascular patency/permeability, and thereby macromolecule delivery. However, patient tumor isolates vary in their responsiveness, and responders show co-induction of epithelial–mesenchymal transition (EMT). We aimed to identify the signal derangements responsible for EMT induction and reverse them and devise approaches to stratify SHHi-responsive tumors noninvasively based on clinically-quantifiable parameters.

Experimental Design:
Animals underwent diffusion-weighted magnetic resonance (DW-MR) imaging for measurement of intratumor diffusivity. In parallel, tissue-level deposition of nanoparticle probes was quantified as a marker of vascular permeability/perfusion. Transcriptomic and bioinformatic analysis was employed to investigate SHHi-induced gene reprogramming and identify key “nodes” responsible for EMT induction.

Results:
Multiple patient tumor isolates responded to short-term SHH inhibitor exposure with increased vascular patency and permeability, with proportionate increases in tumor diffusivity. Nonresponding PDXs did not. SHHi-treated tumors showed elevated FGF drive and distinctly higher nuclear localization of fibroblast growth factor receptor (FGFR1) in EMT-polarized tumor cells. Pan-FGFR inhibitor NVP-BGJ398 (Infigratinib) reversed the SHHi-induced EMT marker expression and nuclear FGFR1 accumulation without compromising the enhanced permeability effect.

Conclusions:
This dual-hit strategy of SMO and FGFR inhibition provides a clinically-translatable approach to compromise the profound impermeability of PDAC tumors. Furthermore, clinical deployment of DW-MR imaging could fulfill the essential clinical–translational requirement for patient stratification.
Profibrotic VEGFR3-Dependent Lymphatic Vessel Growth in Autoimmune Valvular Carditis
Authors: Osinski Victoria , Yellamilli Amritha , Firulyova Maria M. , Zhang Michael J. , Peck Alyssa L. , Auger Jennifer L. , Faragher Jessica L. , Marath Aubyn , Voeller Rochus K. , O’Connell Timothy D. , Zaitsev Konstantin , Binstadt Bryce A. 
Published: January 2024

BACKGROUND:
Rheumatic heart disease is the major cause of valvular heart disease in developing nations. Endothelial cells (ECs) are considered crucial contributors to rheumatic heart disease, but greater insight into their roles in disease progression is needed.

METHODS:

We used a
Cdh5
-driven EC lineage-tracing approach to identify and track ECs in the K/B.g7 model of autoimmune valvular carditis. Single-cell RNA sequencing was used to characterize the EC populations in control and inflamed mitral valves. Immunostaining and conventional histology were used to evaluate lineage tracing and validate single-cell RNA-sequencing findings. The effects of VEGFR3 (vascular endothelial growth factor receptor 3) and VEGF-C (vascular endothelial growth factor C) inhibitors were tested in vivo. The functional impact of mitral valve disease in the K/B.g7 mouse was evaluated using echocardiography. Finally, to translate our findings, we analyzed valves from human patients with rheumatic heart disease undergoing mitral valve replacements.

RESULTS:
Lineage tracing in K/B.g7 mice revealed new capillary lymphatic vessels arising from valve surface ECs during the progression of disease in K/B.g7 mice. Unsupervised clustering of mitral valve single-cell RNA-sequencing data revealed novel lymphatic valve ECs that express a transcriptional profile distinct from other valve EC populations including the recently identified PROX1 (Prospero homeobox protein 1)+ lymphatic valve ECs. During disease progression, these newly identified lymphatic valve ECs expand and upregulate a profibrotic transcriptional profile. Inhibiting VEGFR3 through multiple approaches prevented expansion of this mitral valve lymphatic network. Echocardiography demonstrated that K/B.g7 mice have left ventricular dysfunction and mitral valve stenosis. Valve lymphatic density increased with age in K/B.g7 mice and correlated with worsened ventricular dysfunction. Importantly, human rheumatic valves contained similar lymphatics in greater numbers than nonrheumatic controls.

CONCLUSIONS:
These studies reveal a novel mode of inflammation-associated, VEGFR3-dependent postnatal lymphangiogenesis in murine autoimmune valvular carditis, with similarities to human rheumatic heart disease.
Association of Mean Upper Cervical Spinal Cord Cross-Sectional Area With Cerebral Small Vessel Disease: A Community-Based Cohort Study
Authors: Meng Yufei , Wang Suying , Zhu Wanlin , Wang Tingting , Liu Dandan , Wang Mengxing , Pi Jingtao , Liu Yaou , Zhuo Zhizheng , Pan Yuesong , Wang Yilong 
Published: January 2024

BACKGROUND:
The purpose of this study was to investigate the association between the mean upper cervical spinal cord cross-sectional area (MUCCA) and the risk and severity of cerebral small vessel disease (CSVD).

METHODS:
Community-dwelling residents in Lishui City, China, from the cross-sectional survey in the PRECISE cohort study (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) conducted from 2017 to 2019. We included 1644 of 3067 community-dwelling adults in the PRECISE study after excluding those with incorrect, incomplete, insufficient, or missing clinical or imaging data. Total and modified total CSVD scores, as well as magnetic resonance imaging features, including white matter hyperintensity, lacunes, cerebral microbleeds, enlarged perivascular spaces, and brain atrophy, were assessed at the baseline. The Spinal Cord Toolbox was used to measure the upper cervical spinal cord cross-sectional area of the C1 to C3 segments of the spinal cord and its average value was taken as MUCCA. Participants were divided into 4 groups according to quartiles of MUCCA. Associations were analyzed using linear regression models adjusted for age, sex, current smoking and drinking, medical history, intracranial volume, and total cortical volume.

RESULTS:

The means±SD age of the participants was 61.4±6.5 years, and 635 of 1644 participants (38.6%) were men. The MUCCA was smaller in patients with CSVD than those without CSVD. Using the total CSVD score as a criterion, the MUCCA was 61.78±6.12 cm
2
in 504 of 1644 participants with CSVD and 62.74±5.94 cm
2
in 1140 of 1644 participants without CSVD. Using the modified total CSVD score, the MUCCA was 61.81±6.04 cm
2
in 699 of 1644 participants with CSVD and 62.91±5.94 cm
2
in 945 of 1644 without CSVD. There were statistical differences between the 2 groups after adjusting for covariates in 3 models. The MUCCA was negatively associated with the total and modified total CSVD scores (adjusted β value, −0.009 [95% CI, −0.01 to −0.003] and −0.007 [95% CI, −0.01 to −0.0006]) after adjustment for covariates. Furthermore, the MUCCA was negatively associated with the white matter hyperintensity burden (adjusted β value, −0.01 [95% CI, −0.02 to −0.003]), enlarged perivascular spaces in the basal ganglia (adjusted β value, −0.005 [95% CI, −0.009 to −0.001]), lacunes (adjusted β value, −0.004 [95% CI, −0.007 to −0.0007]), and brain atrophy (adjusted β value, −0.009 [95% CI, −0.01 to −0.004]).

CONCLUSIONS:
The MUCCA and CSVD were correlated. Spinal cord atrophy may serve as an imaging marker for CSVD; thus, small vessel disease may involve the spinal cord in addition to being intracranial.
Disentangling the neural correlates of semantic and domain-general control: The roles of stimulus domain and task process
Authors: Hodgson Victoria J. , Ralph Matthew A. Lambon , Jackson Rebecca L. 
Published: January 2024

Abstract
Control processes are critical for the context-appropriate use of meaningful stimuli. Similar definitions have been adopted in two distinct literatures focusing on identifying the neural correlates of “semantic control” and of executive control across domains (the “multiple demand network”). Surprisingly, despite their proposed functions varying only in relation to domain-specificity, these networks appear to differ anatomically. However, prior comparisons are confounded by variations in task design. To what extent might varying task requirements drive differences in activation patterns that are typically attributed to stimulus domain? Here, for the first time, we use functional MRI to disentangle the effects of task process and stimulus domain during cognitively demanding tasks. Participants performed an odd-one-out task requiring rule-switching, inhibition and selection processes, and an n-back working memory task, each with meaningful semantic and non-semantic stimuli, in a factorial design. Both stimulus domain and task process affected the control regions activated, indicating that task process is indeed a key factor confounding prior studies. However, core semantic control regions (left inferior frontal gyrus, left posterior temporal cortex) also showed a preference for semantic stimuli even with matched task processes, while more peripheral semantic control regions, overlapping the multiple demand network (dorsomedial prefrontal cortex, right inferior frontal gyrus), showed little preference across task or stimulus. Conversely, most multiple demand network regions were preferentially engaged for non-semantic stimuli. These results highlight the mutual importance of stimulus domain and task process in driving variation in control region engagement, both across and between semantic control and multiple demand networks.
Allah, God, YHWH, Gott*: Language-Aware Perspectives on References to God in Religious and Worldview Education. A Comparative Study of Finnish and German School Textbooks
Authors: Putkonen Niina , Tacke Lena 
Published: January 2024

Abstract
Language awareness is part of religious and worldview education. In this study, we understand religious and worldview education as language-sensitive and argue that it is necessary to investigate the perspectives on religious language in language-aware school pedagogy. In our view, religious language can be an identity marker which navigates and reflects one’s position. We analysed the language used in Finnish and German secondary school textbooks for the Lutheran religion, the Roman Catholic religion and for Islam as well as for the subject culture, worldview and ethics (Finland) and practical philosophy (Germany). Using discourse analysis, we examined the representations of God in the textbooks’ chapters about Judaism, Christianity and Islam, which are characterized as monotheistic religions. According to the findings in this study, representations of God in the textbooks refer to the self-understanding of the studied religion in RE. This study also shows that the use of the name of God in textbooks illustrates similarities and differences in Abrahamic religions. We argue that inter-worldview learning in the context of religious and worldview education enables participation, dialogue and encounter, and that language awareness is part of inter-worldview learning.
Collating and Interpreting the Medical Bamboo Slips Excavated from the Han Tombs in Tianhui Town
Authors: Gu Man 
Published: January 2024

Abstract
In July 2012 through August 2013, four earthen shaft pit tombs with timber chambers were excavated in a cemetery located in Tianhui Town, Jinniu District, Chengdu City. The tombs, which had been looted, were of similar size and aligned in the same south–north orientation. Tomb M3 contained 951 bamboo slips distributed across two compartments of its lower chambers: North II and South II. Most of the texts they contain are of medical interest, though twenty fragments appear to be from legal documents. Based on the content of the discovered slips, it has been suggested that the tomb’s occupant was a physician or medical official. Six of the M3–121 manuscripts found in North II concern medical theory, the causes and symptoms of disease, the nature of the channels of the body (mai 脈), diagnosis, acupuncture, and possibly moxibustion therapy. The dates the texts were transcribed fall within the period when Empress Lü 呂后 (187–181 BCE) was effectively in power and the reign of Emperor Wendi (r. 180–157 BCE) of the Western Han dynasty. The M3–137 manuscripts found in South II include two texts entitled the Book of Treating Horses and the Book of the Classic Channels. The dates the texts were copied were earlier than those assigned to the M3–121 manuscripts.
Investigating the Clan Affiliations of the Occupants of the Laoguanshan 老官山 Han Tombs in Chengdu
Authors: Xie Tao , Yang Dolly 
Published: January 2024

Abstract
Inscriptions on funerary objects excavated from the Han tombs of Laoguanshan in Chengdu are key to unraveling the identities of the tombs’ occupants. Our analysis of these inscriptions, considered alongside the varying configurations of the tombs, the excavated objects, the earliest dates when the tombs were ransacked, and the physical characteristics revealed by the bones of the tomb occupants, together suggest that they were aristocrats from different regions. They were “out of state” officials who had immigrated to Chengdu. Identifying their clan affiliations provides an important clue for determining the clan affiliations of occupants of other high-specification tombs found in the Chengdu plain.
Practitioner Responses to the Tianhui Laoguanshan Medical Manuscripts and Artifacts
Authors: Neal Edward , He George 
Published: January 2024

Abstract
In the process of editing this special double issue of Asian Medicine we were keen to print the responses of practitioners of Chinese medicine currently still in practice. We therefore sent colleagues the article by Gu Man, Zhou Qi, and Liu Changhua, “Techniques for Piercing the Mai Recorded in the Laoguanshan Han Tomb Bamboo Slips” and the article by Zhou Qi, “Research on the Lacquered Channel Figurine Excavated from a Han Tomb in Tianhui” while they were in preparation. We are very grateful to Edward Neal and George He for their generous responses. —Eds.
Preliminary Report on the Tianhui Bamboo Manuscript Methods of Decoctions with Blended Formulas to Treat Sixty Ailments
Authors: Luo Qiong , Gu Man , Liu Changhua , Yang Dolly 
Published: January 2024

Abstract
Among the medical manuscripts excavated in 2012–13 from the Han tombs at Tianhui Township in Sichuan Province is a collection of recipes for treating sixty ailments. Under each ailment heading are one or more recipes, making 106 recipes in total. Because its content focuses on “combining, blending and producing formulas,” the authors decided to name this collection the Methods of Decoctions with Blended Formulas to Treat Sixty Ailments after a title of a manuscript transmitted to Cang Gong as recorded in the “Biographies of Bian Que and Cang Gong” chapter of the Records of the Grand Historian, circa 100 BCE. The key phrase in this title, “methods of decoctions with blended formulas,” refers to methods of blending and harmonizing formulas optimally. This Tianhui manuscript preserves ancient medical recipes that had been long lost, including grain decoctions, alcoholic decoctions, and “fire formulas.” It is an invaluable source for charting the emergence of a genre of “classical formularies” in Han times that resulted in texts such as the Classical Methods of Decoctions, the title of which was noted in an ancient bibliography but until recently was thought to be entirely lost.