bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity
Authors: Bläsius Katharina , Ludwig Lena , Knapp Sarah , Flaßhove Charlotte , Sonnabend Friederike , Keller Diandra , Tacken Nikola , Gao Xintong , Kahveci-Türköz Selcan , Grannemann Caroline , Babendreyer Aaron , Adrain Colin , Huth Sebastian , Baron Jens Malte , Ludwig Andreas , Düsterhöft Stefan 
Published: February 2024

AbstractThe protease ADAM17 plays an important role in inflammation and cancer and is regulated by iRhom2. Mutations in the cytosolic N-terminus of human iRhom2 cause tylosis with oesophageal cancer (TOC). In mice, partial deletion of the N-terminus results in a curly hair phenotype (cub). These pathological consequences are consistent with our findings that iRhom2 is highly expressed in keratinocytes and in oesophageal cancer. Cub and TOC are associated with hyperactivation of ADAM17-dependent EGFR signalling. However, the underlying molecular mechanisms are not understood. We have identified a non-canonical, phosphorylation-independent 14-3-3 interaction site that encompasses all known TOC mutations. Disruption of this site dysregulates ADAM17 activity. The larger cub deletion also includes the TOC site and thus also dysregulated ADAM17 activity. The cub deletion, but not the TOC mutation, also causes severe reductions in stimulated shedding, binding, and stability of ADAM17, demonstrating the presence of additional regulatory sites in the N-terminus of iRhom2. Overall, this study contrasts the TOC and cub mutations, illustrates their different molecular consequences, and reveals important key functions of the iRhom2 N-terminus in regulating ADAM17.
High-resolution mapping of Ryd4Hb, a major resistance gene to Barley yellow dwarf virus from Hordeum bulbosum
Authors: Pidon Hélène , Ruge-Wehling Brigitte , Will Torsten , Habekuß Antje , Wendler Neele , Oldach Klaus , Maasberg-Prelle Anja , Korzun Viktor , Stein Nils 
Published: February 2024

Abstract
Key message
We mapped Ryd4Hb in a 66.5 kbp interval in barley and dissociated it from a sublethality factor. These results will enable a targeted selection of the resistance in barley breeding.

Abstract
Virus diseases are causing high yield losses in crops worldwide. The Barley yellow dwarf virus (BYDV) complex is responsible for one of the most widespread and economically important viral diseases of cereals. While no gene conferring complete resistance (immunity) has been uncovered in the primary gene pool of barley, sources of resistance were searched and identified in the wild relative Hordeum bulbosum, representing the secondary gene pool of barley. One such locus, Ryd4Hb, has been previously introgressed into barley, and was allocated to chromosome 3H, but is tightly linked to a sublethality factor that prevents the incorporation and utilization of Ryd4Hb in barley varieties. To solve this problem, we fine-mapped Ryd4Hb and separated it from this negative factor. We narrowed the Ryd4Hb locus to a corresponding 66.5 kbp physical interval in the barley ‘Morex’ reference genome. The region comprises a gene from the nucleotide-binding and leucine-rich repeat immune receptor family, typical of dominant virus resistance genes. The closest homolog to this Ryd4Hb candidate gene is the wheat Sr35 stem rust resistance gene. In addition to the fine mapping, we reduced the interval bearing the sublethality factor to 600 kbp in barley. Aphid feeding experiments demonstrated that Ryd4Hb provides a resistance to BYDV rather than to its vector. The presented results, including the high-throughput molecular markers, will permit a more targeted selection of the resistance in breeding, enabling the use of Ryd4Hb in barley varieties.
Elevated ITGA1 levels in type 2 diabetes: implications for cardiac function impairment
Authors: Su Mengqi , Hou Yilin , Cai Sidong , Li Wenpeng , Wei Yinxia , Wang Run , Wu Min , Liu Mingya , Chang Junlei , Yang Kelaier , Yiu Kaihang , Chen Cong 
Published: February 2024

Abstract
Aims/hypothesis
Type 2 diabetes mellitus is known to contribute to the development of heart failure with preserved ejection fraction (HFpEF). However, identifying HFpEF in individuals with type 2 diabetes early on is often challenging due to a limited array of biomarkers. This study aims to investigate specific biomarkers associated with the progression of HFpEF in individuals with type 2 diabetes, for the purpose of enabling early detection and more effective management strategies.

Methods
Blood samples were collected from individuals with type 2 diabetes, both with and without HFpEF, for proteomic analysis. Plasma integrin α1 (ITGA1) levels were measured and compared between the two groups. Participants were further categorised based on ITGA1 levels and underwent detailed transthoracic echocardiography at baseline and during a median follow-up period of 30 months. Multivariable linear and Cox regression analyses were conducted separately to assess the associations between plasma ITGA1 levels and changes in echocardiography indicators and re-hospitalisation risk. Additionally, proteomic data for the individuals’ left ventricles, from ProteomeXchange database, were analysed to uncover mechanisms underlying the change in ITGA1 levels in HFpEF.

Results
Individuals with type 2 diabetes and HFpEF showed significantly higher plasma ITGA1 levels than the individuals with type 2 diabetes without HFpEF. These elevated ITGA1 levels were associated with left ventricular remodelling and impaired diastolic function. Furthermore, during a median follow-up of 30 months, multivariable analysis revealed that elevated ITGA1 levels independently correlated with deterioration of both diastolic and systolic cardiac functions. Additionally, higher baseline plasma ITGA1 levels independently predicted re-hospitalisation risk (HR 2.331 [95% CI 1.387, 3.917], p=0.001). Proteomic analysis of left ventricular myocardial tissue provided insights into the impact of increased ITGA1 levels on cardiac fibrosis-related pathways and the contribution made by these changes to the development and progression of HFpEF.

Conclusions/interpretation
ITGA1 serves as a biomarker for monitoring cardiac structural and functional damage, can be used to accurately diagnose the presence of HFpEF, and can be used to predict potential deterioration in cardiac structure and function as well as re-hospitalisation for individuals with type 2 diabetes. Its measurement holds promise for facilitating risk stratification and early intervention to mitigate the adverse cardiovascular effects associated with diabetes.

Data availability
The proteomic data of left ventricular myocardial tissue from individuals with type 2 diabetes, encompassing both those with and without HFpEF, is available from the ProteomeXchange database at http://proteomecentral.proteomexchange.org.

Graphical Abstract
Generic vanishing, 1-forms, and topology of Albanese maps
Authors: Dutta Yajnaseni , Hao Feng , Liu Yongqiang 
Published: February 2024

AbstractGiven a bounded constructible complex of sheaves $$\mathcal {F}$$
F
on a complex Abelian variety, we prove an equality relating the cohomology jump loci of $$\mathcal {F}$$
F
and its singular support. As an application, we identify two subsets of the set of holomorphic 1-forms with zeros on a complex smooth projective irregular variety X; one from Green-Lazarsfeld’s cohomology jump loci and one from the Kashiwara’s estimates for singular supports. This result is related to Kotschick’s conjecture about the equivalence between the existence of nowhere vanishing global holomorphic 1-forms and the existence of a fibre bundle structure over the circle. Our results give a conjecturally equivalent formulation using singular support, which is equivalent to a criterion involving cohomology jump loci proposed by Schreieder. As another application, we reprove a recent result proved by Schreieder and Yang; namely if X has simple Albanese variety and admits a fibre bundle structure over the circle, then the Albanese morphism cohomologically behaves like a smooth morphism with respect to integer coefficients. In a related direction, we address the question whether the set of 1-forms that vanish somewhere is a finite union of linear subspaces of $$H^0(X,\Omega _X^1)$$

H
0

(
X
,

Ω
X
1

)

. We show that this is indeed the case for forms admitting zero locus of codimension 1.
S-Duality and the Universal Isometries of Instanton Corrected q-Map Spaces
Authors: Cortés Vicente , Tulli Iván 
Published: February 2024

AbstractGiven a conical affine special Kähler manifold together with a compatible mutually local variation of BPS structures, one can construct a quaternionic-Kähler (QK) manifold. We call the resulting QK manifold an instanton corrected c-map space. Our main aim is to study the isometries of a subclass of instanton corrected c-map spaces associated to projective special real manifolds with a compatible mutually local variation of BPS structures. We call the latter subclass instanton corrected q-map spaces. In the setting of Calabi–Yau compactifications of type IIB string theory, instanton corrected q-map spaces are related to the hypermultiplet moduli space metric with perturbative corrections, together with worldsheet, D(-1) and D1 instanton corrections. In the physics literature, it has been shown that the hypermultiplet metric with such corrections must have an $$\textrm{SL}(2,{\mathbb {Z}})$$

SL
(
2
,
Z
)

acting by isometries, related to S-duality. We give a mathematical treatment of this result, specifying under which conditions instanton corrected q-map spaces carry an action by isometries by $$\textrm{SL}(2,{\mathbb {Z}})$$

SL
(
2
,
Z
)

or some of its subgroups. We further study the universal isometries of instanton corrected q-map spaces, and compare them to the universal isometries of tree-level q-map spaces. Finally, we give an explicit example of a non-trivial instanton corrected q-map space with full $$\textrm{SL}(2,{\mathbb {Z}})$$

SL
(
2
,
Z
)

acting by isometries and admitting a quotient of finite volume by a discrete group of isometries.
Production of recombinant vesicular stomatitis virus-based vectors by tangential flow depth filtration
Authors: Göbel Sven , Pelz Lars , Silva Cristina A. T. , Brühlmann Béla , Hill Charles , Altomonte Jennifer , Kamen Amine , Reichl Udo , Genzel Yvonne 
Published: February 2024

Abstract
Cell culture-based production of vector-based vaccines and virotherapeutics is of increasing interest. The vectors used not only retain their ability to infect cells but also induce robust immune responses. Using two recombinant vesicular stomatitis virus (rVSV)-based constructs, we performed a proof-of-concept study regarding an integrated closed single-use perfusion system that allows continuous virus harvesting and clarification.
Using suspension BHK-21 cells and a fusogenic oncolytic hybrid of vesicular stomatitis virus and Newcastle disease virus (rVSV-NDV), a modified alternating tangential flow device (mATF) or tangential flow depth filtration (TFDF) systems were used for cell retention. As the hollow fibers of the former are characterized by a large internal lumen (0.75 mm; pore size 0.65 μm), membrane blocking by the multi-nucleated syncytia formed during infection could be prevented. However, virus particles were completely retained. In contrast, the TFDF filter unit (lumen 3.15 mm, pore size 2–5 μm) allowed not only to achieve high viable cell concentrations (VCC, 16.4–20.6×106 cells/mL) but also continuous vector harvesting and clarification. Compared to an optimized batch process, 11-fold higher infectious virus titers were obtained in the clarified permeate (maximum 7.5×109 TCID50/mL).
Using HEK293-SF cells and a rVSV vector expressing a green fluorescent protein, perfusion cultivations resulted in a maximum VCC of 11.3×106 cells/mL and infectious virus titers up to 7.1×1010 TCID50/mL in the permeate. Not only continuous harvesting but also clarification was possible. Although the cell-specific virus yield decreased relative to a batch process established as a control, an increased space-time yield was obtained.

Key points
• Viral vector production using a TFDF perfusion system resulted in a 460% increase in space-time yield
• Use of a TFDF system allowed continuous virus harvesting and clarification
• TFDF perfusion system has great potential towards the establishment of an intensified vector production
Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial)
Authors: Zhu Hai-Dong , Li Xiao , Sun Jun-Hui , Zhu Xu , Liu Zhao-Yu , Li Hai-Liang , Lu Jian , Yan Zhi-Ping , Shao Guo-Liang , He Xiao-Feng , Chao Min , Lu Li-Gong , Zhong Bin-Yan , Li Rui , Zhang Qi , Teng Gao-Jun 
Published: February 2024

Abstract
Purpose
While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 μm) microspheres loaded with epirubicin.

Materials and Methods
This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30–50), 75 (range, 60–90), or 100 (range, 75–125) μm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events.

Results
Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death.

Conclusion
DEB-TACE using epirubicin-loaded small-sized (≤ 100 μm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC.

Trial Registration
Clinicaltrials.gov NCT03113955; registered April 14, 2017.
Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017.

Level of evidence
2, Prospective, Non-randomized, Single-arm, study.

Graphical Abstract
Treatment with the apoptosis inhibitor Asunercept reduces clone sizes in patients with lower risk Myelodysplastic Neoplasms
Authors: Streuer Alexander , Jann Johann-Christoph , Boch Tobias , Mossner Maximilian , Riabov Vladimir , Schmitt Nanni , Altrock Eva , Xu Qingyu , Demmerle Marie , Nowak Verena , Oblaender Julia , Palme Iris , Weimer Nadine , Rapp Felicitas , Metzgeroth Georgia , Hecht Anna , Höger Thomas , Merz Christian , Hofmann Wolf-Karsten , Nolte Florian , Nowak Daniel 
Published: February 2024

AbstractIn low-risk Myelodysplastic Neoplasms (MDS), increased activity of apoptosis-promoting factors such as tumor necrosis factor (TNFα) and pro-apoptotic Fas ligand (CD95L) have been described as possible pathomechanisms leading to impaired erythropoiesis. Asunercept (APG101) is a novel therapeutic fusion protein blocking CD95, which has previously shown partial efficacy in reducing transfusion requirement in a clinical phase I trial for low-risk MDS patients (NCT01736436; 2012-11-26). In the current study we aimed to evaluate the effect of Asunercept therapy on the clonal bone marrow composition to identify potential biomarkers to predict response. Bone marrow samples of n = 12 low-risk MDS patients from the above referenced clinical trial were analyzed by serial deep whole exome sequencing in a total of n = 58 time points. We could distinguish a mean of 3.5 molecularly defined subclones per patient (range 2–6). We observed a molecular response defined as reductions of dominant clone sizes by a variant allele frequency (VAF) decrease of at least 10% (mean 20%, range: 10.5–39.2%) in dependency of Asunercept treatment in 9 of 12 (75%) patients. Most of this decline in clonal populations was observed after completion of 12 weeks treatment. Particularly early and pronounced reductions of clone sizes were found in subclones driven by mutations in genes involved in regulation of methylation (n = 1 DNMT3A, n = 1 IDH2, n = 1 TET2). Our results suggest that APG101 could be efficacious in reducing clone sizes of mutated hematopoietic cells in the bone marrow of Myelodysplastic Neoplasms, which warrants further investigation.
Pediatric ping-pong skull fractures treated with vacuum-assisted elevation
Authors: Ahmed Syed D. , Allhusen Virginia D. , Muhonen Michael G. , Magge Suresh N. 
Published: February 2024

Abstract
Purpose
Depressed (“ping-pong”) skull fractures can be treated by different means, including observation, non-surgical treatments, or surgical intervention. The authors describe their experience with vacuum-assisted elevation of ping-pong skull fractures and evaluate variables associated with surgical outcomes.

Methods
The authors present a retrospective review of all ping-pong skull fractures treated with vacuum-assisted elevation at the Children’s Hospital of Orange County in 2021–2022. Variables included patient age, mechanism of injury, fracture depth, bone thickness at the fracture site, and degree of elevation.

Results
Seven patients underwent vacuum-assisted elevation of ping-pong fractures at the bedside without the use of anesthesia. Fractures caused by birth-related trauma were deeper than those caused by falls (p < 0.001). There was no significant difference between groups in bone thickness at the fracture site (2.10 mm vs 2.16 mm, n.s). Six of the seven patients experienced significant improvement in fracture site depression, with four displaying a complete fracture reduction and two displaying a significant reduction. The degree of fracture reduction was modestly related to the depth of fracture, with the two deepest fractures failing to achieve full reduction. Age appeared to be related to fracture reduction, with the lowest reduction observed in one of the oldest patients in this sample. No complications were observed in any patient other than temporary mild swelling at the suction site, and no re-treatment or surgery for the fractures was required.

Conclusion
Vacuum-assisted elevation of ping-pong skull fractures is a safe and effective noninvasive treatment option for infants that can be used under certain circumstances. The procedure can be done safely at the bedside and is a relatively quick procedure. It avoids the need for open surgical intervention, anesthesia, or hospital admission, and can lead to excellent outcomes.
Effect of preoperative oral carbohydrates on insulin resistance in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial
Authors: Wang Xiaohan , Zhuang Jingwen , Cheng Jianxin , Wang Zeyang , Sheng Jingyi , Guo Shanshan , Wang Rui , Wang Zhiping 
Published: February 2024

Abstract
Purpose
The present research seeks to clarify the consequences of two specific preoperative oral carbohydrate (POC) amounts on insulin resistance (IR) and stomach evacuation in laparoscopic cholecystectomy (LC) patients.

Methods
A total of 129 patients set for elective LC procedures were randomly assigned to a control group (C, n = 45), a 200 mL POC group (P1, n = 42), and a 400 mL POC group (P2, n = 42). The C group was fasted from midnight until surgery, whereas the P1 and P2 groups received their respective carbohydrate volumes 2–4 h before anesthesia. Fasting blood glucose, insulin, and glucagon concentrations were measured at three junctures. IR metrics were derived by employing the homeostasis model assessment. Gastric volume was measured before anesthesia using gastric ultrasound. Inter-group comparisons included IR indicators, subjective comfort scores, and hemodynamic data.

Results
At T2, the C group exhibited reduced glucose concentrations compared to the P2 group (4.73 ± 0.64 vs. 5.26 ± 1.02 mmol/L, p < 0.05). The Perlas grading indicated that grade 1 was more prevalent in the P2 group than in the P1 and C groups (18 [42.9%] vs. 6 [14.3%] and 1 [2.2%], p < 0.05). Additionally, thirst and hunger metrics for the P2 group were notably reduced compared to the C group at both T2 and T3.

Conclusion
Administering either 200 mL or 400 mL of carbohydrates 2–4 h pre-surgery had no detectable impact on IR or gastric volume in LC patients.

Trial registration
ChiCTR, ChiCTR2200065648. Registered January 13, 2023, http://www.chictr.org.cn.
Clinicopathological features and prognosis of primary small bowel adenocarcinoma: a large multicenter analysis of the JSCCR database in Japan
Authors: Yamashita Ken , Oka Shiro , Yamada Takeshi , Mitsui Keigo , Yamamoto Hironori , Takahashi Keiichi , Shiomi Akio , Hotta Kinichi , Takeuchi Yoji , Kuwai Toshio , Ishida Fumio , Kudo Shin-Ei , Saito Shoichi , Ueno Masashi , Sunami Eiji , Yamano Tomoki , Itabashi Michio , Ohtsuka Kazuo , Kinugasa Yusuke , Matsumoto Takayuki , Sugai Tamotsu , Uraoka Toshio , Kurahara Koichi , Yamaguchi Shigeki , Kato Tomohiro , Okajima Masazumi , Kashida Hiroshi , Akagi Yoshito , Ikematsu Hiroaki , Ito Masaaki , Esaki Motohiro , Kawai Masaya , Yao Takashi , Hamada Madoka , Horimatsu Takahiro , Koda Keiji , Fukai Yasumori , Komori Koji , Saitoh Yusuke , Kanemitsu Yukihide , Takamaru Hiroyuki , Yamada Kazutaka , Nozawa Hiroaki , Takayama Tetsuji , Togashi Kazutomo , Shinto Eiji , Torisu Takehiro , Toyoshima Akira , Ohmiya Naoki , Kato Takeshi , Otsuji Eigo , Nagata Shinji , Hashiguchi Yojiro , Sugihara Kenichi , Ajioka Yoichi , Tanaka Shinji 
Published: February 2024

Abstract
Background
The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan.

Methods
We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum.

Results
The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7–100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA.

Conclusions
Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.