bluuebunny/crossref_metadata_2025 huggingface dataset:
Cathepsin F and Fibulin-1 as novel diagnostic biomarkers for brain metastasis of non-small cell lung cancer
Authors: Wei Song , Liu Wenwen , Xu Mingxin , Qin Huamin , Liu Chang , Zhang Rui , Zhou Sihai , Li Encheng , Liu Zhiyu , Wang Qi
Published: February 2022

Background

The lack of non-invasive methods for detection of early micro-metastasis is a major cause of the poor prognosis of non-small cell lung cancer (NSCLC) brain metastasis (BM) patients. Herein, we aimed to identify circulating biomarkers based on proteomics for the early diagnosis and monitoring of patients with NSCLC BM.

Methods

Upregulated proteins were detected by secretory proteomics in the animal-derived high brain metastatic lung cancer cell line. A well-designed study composed of three independent cohorts was then performed to verify these blood-based protein biomarkers: the serum discovery and verification cohorts (n = 80; n = 459), and the tissue verification cohort (n = 76). Logistic regression was used to develop a diagnostic biomarker panel. Model validation cohort (n = 160) was used to verify the stability of the constructed predictive model. Changes in serum Cathepsin F (CTSF) levels of patients were tracked to monitor the treatment response. Progression-free survival (PFS) and overall survival (OS) were analysed to assess their prognostic relevance.

Results

CTSF and Fibulin-1 (FBLN1) levels were specifically upregulated in sera and tissues of patients with NSCLC BM compared with NSCLC without BM and primary brain tumour. The combined diagnostic performance of CTSF and FBLN1 was superior to their individual ones. CTSF serum changes were found to reflect the therapeutic response of patients with NSCLC BM and the trends of progression were detected earlier than the magnetic resonance imaging changes. Elevated expression of CTSF in NSCLC BM tissues was associated with poor PFS, and was found to be an independent prognostic factor.

Conclusions

We report a novel blood-based biomarker panel for early diagnosis, monitoring of therapeutic response, and prognostic evaluation of patients with NSCLC BM.
Rapid mold-free fabrication of long functional PDMS fibers
Authors: Lee Jeong Hui , Lim Taekyung , Seo Keumyoung , Park Jeeyin , Yang Jonguk , Jeong Sang-Mi , Ju Sanghyun
Published: February 2022

Polydimethylsiloxane (PDMS), an optically transparent and inert material, is widely used in biological and semiconductor applications owing to its excellent chemical stability and moldability. This study proposes a thermally induced wet spinning method for the fabrication of long PDMS fibers with a constant width. PDMS is a thermoset polymer that undergoes chemical crosslinking when heated, and the thermally induced wet spinning process allows for the formation of fibers without a mold. A rapid thermal curing step was used to instantly solidify the thermoset polymer, where immediate chemical crosslinking of fluid PDMS solution was achieved upon contact with an oil coagulation bath at 180–230 °C. A rapid stretching process was applied to pull out and control the width of the fiber, and the PDMS was stretched at a rate of 1.2–12.5 m/min during the crosslinking process. The fabricated pristine PDMS fibers were transparent and maintained a crosslinked network with excellent mechanical strength. In addition, the PDMS fibers were functionalized with silica nanoparticles, carbon nanotubes, and pores to adjust their transparency/opacity, conductivity, and heat insulation properties, respectively, for various applications. The proposed thermally induced wet spinning method shows promise for overcoming the limitations of existing molding methods, in which the PDMS fibers cannot be lengthened. Furthermore, the process is environmentally friendly and economical owing to the use of edible canola oil, which reduces the volume of harmful solvents and additives during fiber production.
Recent trends in the development of hydrogel therapeutics for the treatment of central nervous system disorders
Authors: Li Qing , Shao Xinxin , Dai Xianglin , Guo Qiong , Yuan Bolei , Liu Ying , Jiang Wei
Published: February 2022

The central nervous system (CNS) controls the acquisition and processing of peripheral information to manage the behaviors of organisms. CNS disorders, including CNS injuries, neurodegenerative diseases, and brain tumors, are devastating and can cause life-long disabilities. Despite the advanced medical interventions in the modern era of biomedical technology, noninvasive therapeutic strategies are still limited for the prevention or reversal of disease progression. Such scarcity is mainly caused by intricate pathological mechanisms and the unique biological microenvironment of the CNS. Thus, the development of a carrier that promotes the delivery of therapeutic agents into the brain is vital. Hydrogels, as a synthetic or natural platform with a porous three-dimensional structure, can be applied as desirable drug delivery vehicles and cell transportation platforms. This review focuses on the most recent advancements in hydrogel-based therapies for the treatment of CNS disorders, including brain injury, spinal cord injury, neurodegenerative diseases, and brain tumors.
Missense mutation of MAL causes a rare leukodystrophy similar to Pelizaeus-Merzbacher disease
Authors: Elpidorou Marilena , Poulter James A. , Szymanska Katarzyna , Baron Wia , Junger Katrin , Boldt Karsten , Ueffing Marius , Green Lydia , Livingston John H. , Sheridan Eammon G. , Johnson Colin A.
Published: February 2022

Leukodystrophies are a heterogenous group of genetic disorders, characterised by abnormal development of cerebral white matter. Pelizaeus-Merzbacher disease is caused by mutations inPLP1, encoding major myelin-resident protein required for myelin sheath assembly. We report a missense variant p.(Ala109Asp) inMALas causative for a rare, hypomyelinating leukodystrophy similar to Pelizaeus-Merzbacher disease.MALencodes a membrane proteolipid that directly interacts with PLP1, ensuring correct distribution during myelin assembly. In contrast to wild-type MAL, mutant MAL was retained in the endoplasmic reticulum but was released following treatment with 4-phenylbutyrate. Proximity-dependent identification of wild-type MAL interactants implicated post-Golgi vesicle-mediated protein transport and protein localisation to membranes, whereas mutant MAL interactants suggested unfolded protein responses. Our results suggest that mislocalisation of MAL affects PLP1 distribution, consistent with known pathomechanisms for hypomyelinating leukodystrophies.
Real life experience with the wearable cardioverter-defibrillator in an international multicenter Registry
Authors: El-Battrawy Ibrahim , Kovacs Boldizsar , Dreher Tobias C. , Klein Norbert , Rosenkaimer Stephanie , Röger Susanne , Kuschyk Jürgen , Saguner Ardan Muammer , Kowitz Jacqueline , Erath Julia W. , Duru Firat , Akin Ibrahim
Published: February 2022

Patients at high risk for sudden cardiac death (SCD) may benefit from wearable cardioverter defibrillators (WCD) by avoiding immediate implantable cardioverter defibrillator (ICD) implantation. Different factors play an important role including patient selection, compliance and optimal drug treatment. We aimed to present real world data from 4 centers from Germany and Switzerland. Between 04/2012 and 03/2019, 708 patients were included in this registry. Patients were followed up over a mean time of 28 ± 35.5 months. Outcome data including gender differences and different etiologies of cardiomyopathy were analyzed. Out of 708 patients (81.8% males, mean age 61.0 ± 14.6), 44.6% of patients had non-ischemic cardiomyopathy, 39.8% ischemic cardiomyopathy, 7.9% myocarditis, 5.4% prior need for ICD explantation and 2.1% channelopathy. The mean wear time of WCD was 21.2 ± 4.3 h per day. In 46% of patients, left ventricular ejection fraction (LVEF) was > 35% during follow-up. The younger the patient was, the higher the LVEF and the lower the wear hours per day were. The total shock rate during follow-up was 2.7%. Whereas an appropriate WCD shock was documented in 16 patients (2.2%), 3 patients received an inappropriate ICD shock (0.5%). During follow-up, implantation of a cardiac implantable electronic device was carried out in 34.5% of patients. When comparing German patients (n = 516) to Swiss patients (n = 192), Swiss patients presented with longer wear days (70.72 ± 49.47 days versus 58.06 ± 40.45 days; p = 0.001) and a higher ICD implantation rate compared to German patients (48.4% versus 29.3%; p = 0.001), although LVEF at follow-up was similar between both groups. Young age is a negative independent predictor for the compliance in this large registry. The most common indication for WCD was non-ischemic cardiomyopathy followed by ischemic cardiomyopathy. The compliance rate was generally high with a decrease of wear hours per day at younger age. Slight differences were found between Swiss and German patients, which might be related to differences in mentality for ICD implantation.
Distribution and safety assessment of heavy metals in fresh meat from Zhejiang, China
Authors: Han Jian Long , Pan Xiao Dong , Chen Qing
Published: February 2022

There are increasing concerns on heavy metals in animal derived foods. We analyzed the levels of As, Cd, Cr, Cu, Hg, Ni, and Pb in 1066 fresh meat samples including pork, beef, mutton, chicken and duck from Zhejiang province, southeast China. The average levels of As, Cd, Cr, Cu, Hg, Ni, and Pb were 0.018, 0.002, 0.061, 0.801, 0.0038, 0.055, and 0.029 mg/kg wet weight respectively. There are significant positive correlations among Cd, Hg and Pb (P < 0.05) and negative correlations for Cu–Pb or Cu–Cd (P < 0.05). The exposure assessment showed that the health risk to humans by consuming these meat products was relatively low. However, regular monitoring of heavy metals in meat products is still recommended considering their intensive industrial activities.
Numerical simulation of bioconvective Darcy Forchhemier nanofluid flow with energy transition over a permeable vertical plate
Authors: Algehyne Ebrahem A. , Areshi Mounirah , Saeed Anwar , Bilal Muhammad , Kumam Wiyada , Kumam Poom
Published: February 2022

In biological systems, the MHD boundary layer bioconvection flow through permeable surface has several applications, including electronic gadgets, heating systems, building thermal insulation, geological systems, renewable energy, electromagnetism and nuclear waste. The bioconvection caused by the hydromagnetic flow of a special form of water-based nanoliquid including motile microorganisms and nanoparticles across a porous upright moving surface is investigated in this report. The combination of motile microbes and nanoparticles causes nanofluid bioconvection is studied under the cumulative impact of magnetic fields and buoyancy forces. The Brownian motion, thermophoresis effects, heat absorption/generation, chemical reaction and Darcy Forchhemier impact are also unified into the nonlinear model of differential equations. The modeled boundary value problem is numerically computed by employing a suitable similarity operation and the parametric continuation procedure. The parametric study of the flow physical parameters is evaluated versus the velocity, energy, volume fraction of nanoparticles, motile microorganisms’ density, skin friction, Sherwood number and Nusselt number. It has been observed that the velocity profile reduces with the effect of porosity parameter k1, inertial parameter k2, Hartmann number and buoyancy ratio. While the energy transition profile significantly enhances with the flourishing values of Eckert number Ec, heat absorption/generation Q and Hartmann number respectively.
Gut Microbiome Characteristics in feral and domesticated horses from different geographic locations
Authors: Ang Li , Vinderola Gabriel , Endo Akihito , Kantanen Juha , Jingfeng Chen , Binetti Ana , Burns Patricia , Qingmiao Shi , Suying Ding , Zujiang Yu , Rios-Covian David , Mantziari Anastasia , Beasley Shea , Gomez-Gallego Carlos , Gueimonde Miguel , Salminen Seppo
Published: February 2022

Domesticated horses live under different conditions compared with their extinct wild ancestors. While housed, medicated and kept on a restricted source of feed, the microbiota of domesticated horses is hypothesized to be altered. We assessed the fecal microbiome of 57 domestic and feral horses from different locations on three continents, observing geographical differences. A higher abundance of eukaryota (p < 0.05) and viruses (p < 0.05) and lower of archaea (p < 0.05) were found in feral animals when compared with domestic ones. The abundance of genes coding for microbe-produced enzymes involved in the metabolism of carbohydrates was significantly higher (p < 0.05) in feral animals regardless of the geographic origin. Differences in the fecal resistomes between both groups of animals were also noted. The domestic/captive horse microbiomes were enriched in genes conferring resistance to tetracycline, likely reflecting the use of this antibiotic in the management of these animals. Our data showed an impoverishment of the fecal microbiome in domestic horses with diet, antibiotic exposure and hygiene being likely drivers. The results offer a view of the intestinal microbiome of horses and the impact of domestication or captivity, which may uncover novel targets for modulating the microbiome of horses to enhance animal health and well-being.
Non-monotonic fluidization generated by fluctuating edge tensions in confluent tissues
Authors: Yamamoto Takaki , Sussman Daniel M. , Shibata Tatsuo , Manning M. Lisa
Published: February 2022

We investigate the dynamical behavior of confluent tissues with fluctuating edge tensions using a cellular vertex model.
Discrimination of commercial ibuprofen tablets by using a button sample holder and mid-infrared spectroscopy
Authors: Singh Jaspreet , White Robert L.
Published: February 2022

A stainless-steel button sample holder is evaluated for pharmaceutical tablet analyses. Small fragments are removed for analysis by abrasion. Neat sample mid-infrared spectra represent formulations.
Sequential quantification of blood and diluent using red cell sedimentation-based separation and pressure-induced work in a microfluidic channel
Authors: Kang Yang Jun
Published: February 2022

Pressure-induced work in the coflowing channel was newly suggested for quantifying both blood and diluent from small blood volume of 50 μL.
Infrared spectroscopy of 2-oxo-octanoic acid in multiple phases
Authors: Kappes Keaten , Frandsen Benjamin N. , Vaida Veronica
Published: February 2022

The chemistry defining inter- and intramolecular interactions available to 2-oxo-octanoic acid in environmentally relevant phases are spectroscopically probed.
Electrochemical gating for single-molecule electronics with hybrid Au|graphene contacts
Authors: Tao Shuhui , Zhang Qian , Vezzoli Andrea , Zhao Cezhou , Zhao Chun , Higgins Simon J. , Smogunov Alexander , Dappe Yannick J. , Nichols Richard J. , Yang Li
Published: February 2022

A ‘‘off–on–off’’ conductance switching of graphene-contacted single molecular junctions has been reported for the first time using the STM-I(s) method under the electrochemical control. Experimental results are discussed against both a phase coherent tunnelling and an incoherent hopping model.
Electromagnetic bioeffects: a multiscale molecular simulation perspective
Authors: Noble Benjamin B. , Todorova Nevena , Yarovsky Irene
Published: February 2022

We summarise methodologies, challenges and opportunities for theoretical modelling to advance current understanding of electromagnetic bioeffects for biomedicine and industry.
Metabolic engineering ofZymomonas mobilisfor continuous co-production of bioethanol and poly-3-hydroxybutyrate (PHB)
Authors: Li Yang , Wang Ying , Wang Ruxiang , Yan Xiongying , Wang Jiewen , Wang Xia , Chen Shouwen , Bai Fengwu , He Qiaoning , Yang Shihui
Published: February 2022

High Heterologous PHB Production and Continuous Anaerobic Ethanol Fermentation using Zymomonas mobilis.
Multiwalled carbon nanotube nanofiller-polyindole polymer matrix-based efficient biosensor for the rapid detection of swine flu
Authors: Nirbhaya Vishakha , Chaudhary Chhaya , Chauhan Dipti , Chandra Ramesh , Kumar Suveen
Published: February 2022

Pictorial representation of the synthesis of the electrode material, fabrication and electrochemical response of the biosensing platform for swine flu detection.
Second harmonic Rayleigh scattering optical activity of single Ag nanohelices in a liquid
Authors: Ohnoutek Lukas , Olohan Ben J. , Jones Robin R. , Zheng Xuezhi , Jeong Hyeon-Ho , Valev Ventsislav K.
Published: February 2022

Second harmonic scattering measures the handedness of single (on average) Ag nanohelices, floating freely in an isotropic liquid.
Electrochromic and photochromic behaviour in a single metal–organic framework containing a redox-active linker
Authors: Radha Govu , Roy Susmita , Chakraborty Chanchal , Aggarwal Himanshu
Published: February 2022

A Zr-based metal organic framework with naphthalene diimide teracarboxylate linkers is reported for its dual electrochromic and photochromic behavior.
Silver-catalyzed chemodivergent assembly of aminomethylated isochromenes and naphthols
Authors: Yu Bangkui , Huang Renbin , Li Renren , Zhang Haocheng , Huang Hanmin
Published: February 2022

A silver-catalyzed chemodivergent cyclization of alkyne-tethered aldehydes with aminals to aminomethylated 1H-isochromenes and naphthols is described by tuning the catalyst system and reaction conditions.
Unlocking the computational design of metal–organic cages
Authors: Tarzia Andrew , Jelfs Kim E.
Published: February 2022

Metal–organic cages are macrocyclic structures that can possess an intrinsic void for application in encapsulation, sensing and catalysis. In this article, we highlight approaches and limitations to their computational design.
A tandem process for the synthesis of β-aminoboronic acids from aziridines with haloamine intermediates
Authors: Park Subin , Koo Jangwoo , Kim Weonjeong , Lee Hong Geun
Published: February 2022

Based on a sequential process of haloamine formation and radical borylation, a novel strategy for synthesizing β-aminoboronic acids is devised.
An intrinsic room-temperature half-metallic ferromagnet in a metal-free PN2 monolayer
Authors: Zhang Quan , Zhang Yang , Li Ying , Fang Dangqi , Che Junwei , Zhang Erhu , Zhang Peng , Zhang Shengli
Published: February 2022

This work proposed an intrinsic metal-free half-metallic ferromagnet, i.e. a PN2 monolayer, which could be a promising candidate for realistic room-temperature metal-free spintronic applications.
Improving the performance of silicon monoxide anodes via tuning a multiple pre-doping system: a first-principles study
Authors: Xie Wei , Pang Chunlei , He Peng , Xiao Chengmao , Koyama Michihisa , Wang Jiantao , Qi Xiaopeng , Ren Jianguo , He Xueqin
Published: February 2022

A multiple pre-doping system with a looser structure displays small fractional volume expansion.
Lewis acid–base adducts of Al(N(C6F5)2)3 and Ga(N(C6F5)2)3 – structural features and dissociation enthalpies
Authors: Kögel Julius F. , Sorokin Denis A. , Scott Martin , Harms Klaus , Himmel Daniel , Krossing Ingo , Sundermeyer Jörg
Published: February 2022

Herein we present the molecular structures of six neutral Lewis acid–base adducts of the Lewis superacid Al(N(C6F5)2)3 and its higher homolog Ga(N(C6F5)2)3 with the electron pair donors MeCN, CNtBu, THF and PMe3.
Nickel -doped iron oxide nanoparticle-conjugated porphyrin interface (porphyrin/Fe2O3@Ni) for the non-enzymatic detection of dopamine from lacrimal fluid
Authors: Amara Umay , Mahmood Khalid , Awais Muhammad , Khalid Muhammad , Nasir Muhammad , Riaz Sara , Hayat Akhtar , Nawaz Mian Hasnain
Published: February 2022

Herein, we synthesized nickel (Ni)-doped iron oxide nanoparticles (Fe2O3).
Chromous siloxides of variable nuclearity and magnetism
Authors: Trzmiel Simon P. O. , Langmann Jan , Maichle-Mössmer Cäcilia , Anwander Reiner
Published: February 2022

The nuclearity {Crn} (n= 1–4) of complexes [Cr(OSiR3)2(Do)x] can be easily tailored, depending on R and presence/type of donor Do.
High-performance PBI membranes for flow batteries: from the transport mechanism to the pilot plant
Authors: Dai Qing , Xing Feng , Liu Xiaonan , Shi Dingqin , Deng Congzhi , Zhao Ziming , Li Xianfeng
Published: February 2022

This work combines fundamental research and real-world application. We systematically investigated the ion transport mechanism of polybenzimidazole (PBI) membranes and developed wide-pH-range applicable PBI membranes from lab scale to pilot plant.
Environmentally friendly catechol-based synthesis of dibenzosultams
Authors: Liljenberg Sara , Nain-Perez Amalyn , Nilsson Oscar , Matic Josipa , Grøtli Morten
Published: February 2022

A scalable reaction for the synthesis of dibenzosultams in water with the aid of K2CO3 and air.
Color-tunable luminescence, energy transfer behavior and I–V characteristics of Dy3+,Eu3+ co-doped La(PO4) phosphors for WLEDs and solar applications
Authors: Parauha Yatish R. , Dhoble S. J.
Published: February 2022

We synthesize different concentrations of Dy3+,Eu3+ doped and co-doped La(PO4) phosphors via the solid-state synthesis and test their photoluminescence and I–V characteristics  for WLEDs and solar panels.
Self-assembly of berberine and a boron cluster for antibacterial regulation
Authors: Peng Zi-Ze , Xu Shi-Yuan , Li Wen-Zhen , Li Lingling , Wang Xiao-Qiang , Wang Wenjing
Published: February 2022

B12H122−and BBR can quickly form rod-shaped particles in aqueous solution with enhanced reactive oxygen species (ROS) generation ability.
Defect-controlled halogenating properties of lanthanide-doped ceria nanozymes
Authors: Opitz Phil , Jegel Olga , Nasir Jamal , Rios-Studer Tobias , Gazanis Athanasios , Pham Dang-Hieu , Domke Katrin , Heermann Ralf , Schmedt auf der Günne Jörn , Tremel Wolfgang
Published: February 2022

Ce1−xLnxO2−x/2 nanocrystals prepared mechanochemically from CeCl3, LnCl3, and Na2CO3 show enhanced haloperoxidase activity. ESR and IR spectroscopy revealed the Ln3+ distribution in the CeO2 host and the presence of Ce3+ and O2− surface species.
Correction: Nanochannel conduction in piezoelectric polymeric membrane using swift heavy ions and nanoclay
Authors: Jana Karun Kumar , Vishwakarma Niraj Kumar , Ray Biswajit , Khan Saif A. , Avasthi Devesh K. , Misra Manjusri , Maiti Pralay
Published: February 2022

Correction for ‘Nanochannel conduction in piezoelectric polymeric membrane using swift heavy ions and nanoclay’ by Karun Kumar Jana et al., RSC Adv., 2013, 3, 6147–6159. DOI: 10.1039/C3RA23176C
An experimental and theoretical study of the inward particle drift in contact line deposits
Authors: Parthasarathy Dinesh , Chandragiri Santhan , Thampi Sumesh P. , Ravindran Parag , Basavaraj Madivala G.
Published: February 2022

The coffee ring effect, which refers to the formation of a ring-like deposit along the periphery of a dried particle-laden sessile drop, is a commonly observed phenomenon. In this article, we document the inward drift of a coffee stain.
WHIRLY1 functions in the nucleus to regulate barley leaf development and associated metabolite profiles
Authors: Karpinska Barbara , Razak Nurhayati , James Euan K. , Morris Jenny A. , Verrall Susan R. , Hedley Peter E. , Hancock Robert D. , Foyer Christine H.
Published: February 2022

The WHIRLY (WHY) DNA/RNA binding proteins fulfil multiple but poorly characterised functions in leaf development. Here, we show that WHY1 transcript levels were highest in the bases of 7-day old barley leaves. Immunogold labelling revealed that the WHY1 protein was more abundant in the nuclei than the proplastids of the leaf bases. To identify transcripts associated with leaf development we conducted hierarchical clustering of differentially abundant transcripts along the developmental gradient of wild-type leaves. Similarly, metabolite profiling was employed to identify metabolites exhibiting a developmental gradient. A comparative analysis of transcripts and metabolites in barley lines (W1–1 and W1–7) lacking WHY1, which show delayed greening compared with the wild type revealed that the transcript profile of leaf development was largely unchanged in W1–1 and W1–7 leaves. However, there were differences in levels of several transcripts encoding transcription factors associated with chloroplast development. These include a barley homologue of the Arabidopsis GATA transcription factor that regulates stomatal development, greening and chloroplast development, NAC1; two transcripts with similarity to Arabidopsis GLK1 and two transcripts encoding ARF transcriptions factors with functions in leaf morphogenesis and development. Chloroplast proteins were less abundant in the W1–1 and W1–7 leaves than the wild type. The levels of tricarboxylic acid cycle metabolites and GABA were significantly lower in WHY1 knockdown leaves than the wild type. This study provides evidence that WHY1 is localised in the nuclei of leaf bases, contributing the regulation of nuclear-encoded transcripts that regulate chloroplast development.
Deletion of Slc6a14 reduces cancer growth and metastatic spread and improves survival in KPC mouse model of spontaneous pancreatic cancer
Authors: Schniers Bradley K. , Wachtel Mitchell S. , Sharma Meenu , Korac Ksenija , Rajasekaran Devaraja , Yang Shengping , Sniegowski Tyler , Ganapathy Vadivel , Bhutia Yangzom D.
Published: February 2022

Pancreatic ductal adenocarcinoma (PDAC) is lethal. There is a dire need for better therapeutic targets. Cancer cells have increased demand for sugars, amino acids, and lipids and therefore up-regulate various nutrient transporters to meet this demand. In PDAC, SLC6A14 (an amino acid transporter (AAT)) is up-regulated, affecting overall patient survival. Previously we have shown using in vitro cell culture models and in vivo xenograft mouse models that pharmacological inhibition of SLC6A14 with α-methyl-l-tryptophan (α-MLT) attenuates PDAC growth. Mechanistically, blockade of SLC6A14-mediated amino acid transport with α-MLT leads to amino acid deprivation, eventually inhibiting mTORC1 signaling pathway, in tumor cells. Here, we report on the effect of Slc6a14 deletion on various parameters of PDAC in KPC mice, a model for spontaneous PDAC. Pancreatic tumors in KPC mice show evidence of Slc6a14 up-regulation. Deletion of Slc6a14 in this mouse attenuates PDAC growth, decreases the metastatic spread of the tumor, reduces ascites fluid accumulation, and improves overall survival. At the molecular level, we show lower proliferation index and reduced desmoplastic reaction following Slc6a14 deletion. Furthermore, we find that deletion of Slc6a14 does not lead to compensatory up-regulation in any of the other amino transporters. In fact, some of the AATs are actually down-regulated in response to Slc6a14 deletion, most likely related to altered mTORC1 signaling. Taken together, these results underscore the positive role SLC6A14 plays in PDAC growth and metastasis. Therefore, SLC6A14 is a viable drug target for the treatment of PDAC and also for any other cancer that overexpresses this transporter.
Exploring cryo-electron microscopy with molecular dynamics
Authors: Vant John W. , Sarkar Daipayan , Nguyen Jonathan , Baker Alexander T. , Vermaas Josh V. , Singharoy Abhishek
Published: February 2022

Single particle analysis cryo-electron microscopy (EM) and molecular dynamics (MD) have been complimentary methods since cryo-EM was first applied to the field of structural biology. The relationship started by biasing structural models to fit low-resolution cryo-EM maps of large macromolecular complexes not amenable to crystallization. The connection between cryo-EM and MD evolved as cryo-EM maps improved in resolution, allowing advanced sampling algorithms to simultaneously refine backbone and sidechains. Moving beyond a single static snapshot, modern inferencing approaches integrate cryo-EM and MD to generate structural ensembles from cryo-EM map data or directly from the particle images themselves. We summarize the recent history of MD innovations in the area of cryo-EM modeling. The merits for the myriad of MD based cryo-EM modeling methods are discussed, as well as, the discoveries that were made possible by the integration of molecular modeling with cryo-EM. Lastly, current challenges and potential opportunities are reviewed.
Understanding the key functions of Myosins in viral infection
Authors: He Jiayi , Qiu Yixing , Tan Lei , Duan Deyong , Yuan Xiaomin , Yang Lingchen , Wang Aibing
Published: February 2022

Myosins, a class of actin-based motor proteins existing in almost any organism, are originally considered only involved in driving muscle contraction, reshaping actin cytoskeleton, and anchoring or transporting cargoes, including protein complexes, organelles, vesicles. However, accumulating evidence reveals that myosins also play vital roles in viral infection, depending on viral species and infection stages. This review systemically summarizes the described various myosins, the performed functions, and the involved mechanisms or molecular pathways during viral infection. Meanwhile, the existing issues are also discussed. Additionally, the important technologies or agents, including siRNA, gene editing, and myosin inhibitors, would facilitate dissecting the actions and mechanisms for described and undescribed myosins, which could be adopted to prevent or control viral infection are also characterized.
The CARMENES search for exoplanets around M dwarfs
Authors: Jeffers S. V. , Barnes J. R. , Schöfer P. , Quirrenbach A. , Zechmeister M. , Amado P. J. , Caballero J. A. , Fernández M. , Rodríguez E. , Ribas I. , Reiners A. , Cardona Guillén C. , Cifuentes C. , Czesla S. , Hatzes A. P. , Kürster M. , Montes D. , Morales J. C. , Pedraz S. , Sadegi S.
Published: February 2022

Context. Current exoplanet surveys using the radial velocity (RV) technique are targeting M dwarfs because any habitable zone terrestrial-mass planets will induce a high RV and orbit on shorter periods than for more massive stars. One of the main caveats is that M dwarfs show a wide range of activity levels from inactive to very active, which can induce an asymmetry in the line profiles and, consequently, a spurious RV measurement.

Aims. We aim to benchmark the impact of stellar activity on high-precision RV measurements using regular-cadence CARMENES visible and near-infrared observations of the active M3.5 dwarf EV Lac.

Methods. We used the newly developed technique of low-resolution Doppler imaging to determine the centre-of-light, or spot-induced RV component, for eight observational epochs.

Results. We confirm a statistically significant and strong correlation between the independently measured centre-of-light and the chromatic index, which is a measure of the amplitude variation with wavelength of the RVs. We also find circular “closed-loop” relations of several activity indices with RV for a subset of data that covers only several rotation periods. We also investigate the implications of large phase gaps in the periodograms of activity indicators. Finally, by removing the spot-induced RV component we improve the planet-mass sensitivity by a factor of at least three.

Conclusions. We conclude that for active M stars, a regular-cadence observing strategy is the most efficient way to identify and eliminate sources of correlated noise.
Detecting deep axisymmetric toroidal magnetic fields in stars
Authors: Dhouib H. , Mathis S. , Bugnet L. , Van Reeth T. , Aerts C.
Published: February 2022

Context. Asteroseismology has revealed small core-to-surface rotation contrasts in stars in the whole Hertzsprung–Russell diagram. This is the signature of strong transport of angular momentum (AM) in stellar interiors. One of the plausible candidates to efficiently carry AM is magnetic fields with various topologies that could be present in stellar radiative zones. Among them, strong axisymmetric azimuthal (toroidal) magnetic fields have received a lot of interest. Indeed, if they are subject to the so-called Tayler instability, the accompanying triggered Maxwell stresses can transport AM efficiently. In addition, the electromotive force induced by the fluctuations of magnetic and velocity fields could potentially sustain a dynamo action that leads to the regeneration of the initial strong axisymmetric azimuthal magnetic field.

Aims. The key question we aim to answer is whether we can detect signatures of these deep strong azimuthal magnetic fields. The only way to answer this question is asteroseismology, and the best laboratories of study are intermediate-mass and massive stars with external radiative envelopes. Most of these are rapid rotators during their main sequence. Therefore, we have to study stellar pulsations propagating in stably stratified, rotating, and potentially strongly magnetised radiative zones, namely magneto-gravito-inertial (MGI) waves.

Methods. We generalise the traditional approximation of rotation (TAR) by simultaneously taking general axisymmetric differential rotation and azimuthal magnetic fields into account. Both the Coriolis acceleration and the Lorentz force are therefore treated in a non-perturbative way. Using this new formalism, we derive the asymptotic properties of MGI waves and their period spacings.

Results. We find that toroidal magnetic fields induce a shift in the period spacings of gravity (g) and Rossby (r) modes. An equatorial azimuthal magnetic field with an amplitude of the order of 105 G leads to signatures that are detectable in period spacings for high-radial-order g and r modes in γ Doradus (γ Dor) and slowly pulsating B (SPB) stars. More complex hemispheric configurations are more difficult to observe, particularly when they are localised out of the propagation region of MGI modes, which can be localised in an equatorial belt.

Conclusions. The magnetic TAR, which takes into account toroidal magnetic fields in a non-perturbative way, is derived. This new formalism allows us to assess the effects of the magnetic field in γ Dor and SPB stars on g and r modes. We find that these effects should be detectable for equatorial fields thanks to modern space photometry using observations from Kepler, TESS CVZ, and PLATO.
Simplified approach to determine the requirements of a “flexible nuclear reactor” in power system with high insertion of variable renewable energy sources
Authors: Mazauric Anne-Laure , Sciora Pierre , Pascal Vincent , Droin Jean-Baptiste , Bésanger Yvon , Hadjsaïd Nouredine , Tran Quoc Tuan , Guyonneau Nicolas
Published: February 2022

The objective of the paper is to study the potential behaviour of a power system with high share of nuclear and less thermal plants, in which variable RES insertion increases − for example the French case −, in order to determine the specifications for the design of a potential nuclear reactor with high “manoeuvrability”. Moreover, the flexible reactor may participate more in the supply − demand balance and in particular during large frequency fluctuations caused by the high variability of RES. The studies are carried out with the PowerFactory software, which make it possible to highlight specific needs regarding the power ramp for an “ideal” flexible nuclear reactor. Using a benchmark network, the Kundur “2 areas-4 machines”, the flexibility requirements are obtained as a function of the grid disturbances. For this purpose, the penetration of variable RES is progressively increased, while nuclear power is reduced and thermal power plants are totally suppressed. The study shows that a drop in RES production directly impacts the minimal frequency. A faster response speed of nuclear power makes it possible to restore this stability and return to normal operating conditions imposed by the grid operator. This paper describes therefore the process of obtaining the flexibility criterion for different cases of insertion of variable RES.
Neugeborenenscreening auf Sichelzellkrankheit
Authors: Lobitz Stephan
Published: February 2022

Die Sichelzellkrankheit (SCD) ist eine schwere angeborene Bluterkrankung, die mit einer hohen Morbidität und Mortalität im Säuglings- und Kleinkindalter einhergeht, wenn sie noch nicht diagnostiziert worden ist. Kritisch sind insbesondere fulminante bakterielle Infektionen im Rahmen der krankheitstypischen Hyposplenie sowie akute Verschlechterungen der im Intervall stabilen Anämie. Mit sehr einfachen Maßnahmen (Schulung, Impfung und Penicillin-Prophylaxe) lässt sich ein Großteil der schweren Komplikationen vermeiden. Da die Erkrankung schon bei Geburt sehr einfach und sehr zuverlässig aus Trockenblut diagnostizierbar ist und zudem inzwischen ein gutes therapeutisches Konzept existiert, gibt es eine gute Rationale für ein Neugeborenenscreening (NBS). International werden Neugeborene teilweise schon seit den frühen 1970er-Jahren auf die SCD untersucht. Das flächendeckende NBS in Deutschland hat am 1. Oktober 2021 begonnen. Dieser Artikel gibt Ihnen einen Überblick über die neue Zielkrankheit.
Effects of Single Manual Medicine Treatment for Infants with Postural
and Movement Asymmetries and Positional Preference: A Multicentre Randomised
Controlled Trial – SMMT for IPMA
Authors: Sacher Robby , Wuttke Marc , Göhmann Ulrich , Kayser Christian , Knabe-Ulner Kirsti , Ammermann Elke , Ammermann Michael , Krocker Bodo , Fünfgeld Liv , Spittank Holger , Derlien Steffen , Loudovici-Krug Dana
Published: February 2022

Objective The aim of the study was the evaluation of the effects of a
single manual medicine treatment (SMMT) for infants with postural and motor
asymmetries in upper cervical asymmetry disorder respectively kinematic
imbalance due to suboccipital strain (KISS).

Methods Design: Multicentre double-blind randomised study
Subjects/Setting: 202 infants at the age of 14–24 weeks with
postural and movement findings were examined in four study centres using the
standardized 4-item Symmetry-Score (points: 4=symmetric to
17=asymmetric). The inclusion criterion was a score of at least 10
points. The intervention group (IG) received a SMMT, whereas the control group
(CG) did not receive any manual therapy. In addition, the infants of both groups
were trained with a home exercise programme by their parents.

Statistical Methods The primary target parameter was the result of the
Symmetry-Score, measured before the intervention and 4–6 weeks
afterwards.

Results 171 children were randomised
(IG=83/CG=88). All infants enrolled were measured to the
second time-point (Intention-to-treat-analysis). The average improvement of IG
compared to CG in Symmetry-Score was 2.3 points (p<.001). Following the
score definition 80% of IG and 49% of CG fell below the
treatment threshold of 10 points. No side effects were observed.

Conclusions The SMMT significantly improves postural and motor asymmetries
in infants with KISS.
Akademisierung und Professionalisierung
Authors: Lange Ute
Published: February 2022

Eine Chance – nicht nur für Hebammen

Das neue Hebammengesetz ist ein wichtiger Schritt zur Professionalisierung des Hebammenberufs. Deutschland ist als letzter EU-Mitgliedsstaat den Empfehlungen der WHO gefolgt, hat die Hebammenausbildung an internationale Standards angepasst und auf Hochschulniveau angehoben.
Ultraschalluntersuchungen in der Kinderrheumatologie
Authors: Roth Johannes , Windschall Daniel
Published: February 2022

Mit zunehmendem Einsatz des Gelenkultraschalls zeigt sich eine stetige Verbesserung der diagnostischen Möglichkeiten bei der Diagnosestellung, Abgrenzung und im Verlaufsmonotoring kindlich rheumatischer Erkrankungen. So können entzündliche Erkrankungen des kindlichen Kniegelenkes hervorragend differenziert und im Verlauf kontrolliert werden. Neben den typischen sonografischen Zeichen einer Gelenkentzündung lassen sich am Kniegelenk auch rheumatische Sehnenansatzentzündungen und Schleimbeutelentzündungen sicher nachweisen. Wichtige Differenzialdiagnosen können bereits sonografisch ausgeschlosssen oder bestätigt werden. Zunehmende Standards helfen bei der praktischen Durchführung, Beurteilung und Quantifizierung des pathologischen Kniegelenkbefundes.
Sarkopenie in der Rheumatologie
Authors: Bühring Björn , Müller Celina , Parvaee Roshnak , Baraliakos Xenofon , Braun Jürgen , Bauhammer Jutta
Published: February 2022

Sarkopenie bezeichnet laut aktueller Definitionen, z. B. der durch die European Working Group on Sarcopenia in Older People (EWGSOP) im Jahre 2019 erstellten Definition, den Verlust an Muskelmasse, -kraft und -leistung. Von einer primären, altersbedingten Sarkopenie wird eine sekundäre unterschieden, zu deren Ursachen Immobilität, inadäquate Ernährung, Medikamente wie Glukokortikoide und systemische Erkrankungen, wie z. B. chronisch entzündliche Erkrankungen zählen. Die in der Literatur berichtete Prävalenz der Sarkopenie bei entzündlich rheumatischen Erkrankungen variiert aufgrund verschiedener Definitionen und untersuchten Populationen stark, beträgt aber bei der rheumatoiden Arthritis ca. 30 %. Neben dem Alter sind erhöhte Entzündungsmediatoren, Glukokortikoid-Therapie, körperliche Inaktivität und Krankheitsdauer weitere Risikofaktoren. Eine Sarkopenie hat direkten Einfluss auf die Mobilität und Eigenständigkeit älterer Menschen. Sie ist assoziiert mit einer erhöhten Gesamtsterblichkeit, Stürzen, Krankenhausaufenthalten sowie weiteren Funktionsparametern des täglichen Lebens. Im Behandlungsalltag kann die Sarkopenie durch einfache Assessments rasch erfasst werden. Therapieoptionen bestehen aus Bewegungs- und Krafttraining sowie einer ausgewogenen, proteinreichen Ernährung.
Hodgkin-Lymphom
Authors: Schmale Ine
Published: February 2022

Beim ASH 2021 wurden verschiedene Studien zur Kombination von Checkpoint-Inhibitoren mit Chemo- und anderen zielgerichteten Therapien bei Patienten mit klassischem Hodgkin-Lymphom vorgestellt. Die zum Teil vielversprechenden Ergebnisse deuten insbesondere auf ein Optimierungspotenzial bei der Patientenselektion und der zeitlichen Therapieplanung hin.
Dual-Layer Spectral Detector CT in Comparison with FDG-PET/CT for the Assessment of Lymphoma Activity
Authors: Gehling Kim , Mokry Theresa , Do Thuy Duong , Giesel Frederik Lars , Dietrich Sascha , Haberkorn Uwe , Kauczor Hans-Ulrich , Weber Tim Frederik
Published: February 2022

Purpose In patients with malignant lymphoma, disease activity is recommended to be assessed by FDG-PET/CT and the Deauville five-point scale (5-PS). The purpose of this study was to explore the potential of iodine concentration measured in contrast-enhanced dual-layer spectral detector CT (SDCT) as an alternative surrogate parameter for lymphoma disease activity by investigating its correlation with maximum standardized uptake values (SUVmax) and 5-PS.

Materials and Methods 25 patients were retrospectively analyzed. Contrast-enhanced SDCT and FDG-PET/CT were performed in the same treatment interval within at most 3 months. CT attenuation values (AV), absolute iodine concentrations (aIC), and normalized iodine concentrations (nIC) of lymphoma lesions were correlated with SUVmax using Spearman’s rank correlation coefficient. The performance of aIC and nIC to detect lymphoma activity (defined as 5-PS > 3) was determined using ROC curves.

Results 60 lesions were analyzed, and 31 lesions were considered active. AV, aIC, and nIC all correlated significantly with SUVmax. The strongest correlation (Spearman ρ = 0.71; p < 0.001) and highest area under the ROC curve (AUROC) for detecting lymphoma activity were observed for nIC normalized to inferior vena cava enhancement (AUROC = 0.866). The latter provided sensitivity, specificity, and diagnostic accuracy of 87 %, 75 %, and 80 %, respectively, at a threshold of 0.20. ROC analysis for AV (AUROC = 0.834) and aIC (AUROC = 0.853) yielded similar results.

Conclusion In malignant lymphomas, there is a significant correlation between metabolic activity as assessed by FDG-PET/CT and iodine concentration as assessed by SDCT. Iodine concentration shows promising diagnostic performance for detecting lymphoma activity and may represent a potential imaging biomarker.

Key Points: 

Citation Format
44. San Antonio Breast Cancer Symposium
Authors: Kretzschmar Alexander
Published: February 2022

Das 44. San Antonio Breast Cancer Symposium (SABCS) fand vom 7. bis 10. Dezember 2021 erstmals im Hybridformat statt. Im Fokus stand die Vorstellung von über 1000 Abstracts zur Prävention, Diagnose und Therapie von Brustkrebs.
Reliability of the Modified Four-Square Step Test in Revision Total
Knee Arthroplasty: A Cross-Sectional Study
Authors: Unver Bayram , Sevik Kevser , Karatosun Vasfi
Published: February 2022

Background The modified four-square step test (mFSST) assesses dynamic
balance by rapid stepping in different directions. This study aimed to evaluate
the reliability of the mFSST in patients who had undergone revision total knee
artroplasty (rTKA).

Methods The study was designed as a cross-sectional study. The mFSST was
administered on 22 patients with a history of rTKA. Two trials were performed
and the patients rested between trials to avoid fatigue.

Results The intraclass correlation coefficient (ICC) for the mFSST was
0.83. The standard error of measurement and the smallest real difference
(95%. confidence level) were 0.67 and 1.85 respectively.

Conclusion The mFSST showed good reliability in patients who had undergone
rTKA. The mFSST is a reliable measure for the assessment of gait variability,
dynamic balance, walking skills and mobility. It can easily detect changes in
rTKA patients with simple equipment.
Endoscopic vacuum therapy (EVT) for acute esophageal perforation: Could it replace surgery?
Authors: Stathopoulos Petros , Zumblick Malte , Wächter Sabine , Schiffmann Leif , Gress Thomas M. , Bartsch Detlef , Seitz Guido , Denzer Ulrike W.
Published: February 2022

Background and study aims Acute esophageal perforation is a potentially life-threating condition that demands a multidisciplinary approach. Based on recently published data indicating that EVT may be effective in managing esophageal perforation, we report our institution’s experience with EVT in this clinical setting.

Patients and methods We retrospectively analyzed all 10 patients with acute esophageal perforation from May 2018 to January 2021, using descriptive statistics. The primary outcome was successful closure of the perforation. Secondary outcomes included the length of treatment, number of endoscopic procedures required, and complication rate.

Results All patients (site of perforation: 4 upper, 2 middle, 4 lower esophagus; etiology: 8 iatrogenic, 2 foreign body ingestion) were treated with EVT successfully. In eight cases, EVT was started immediately after the perforation, in the other two cases 1 and 2 days later. The median (interquartile range) number of endoscopic procedures was 2.5 (range, 2–3) and the median duration of treatment was 7.5 days (range, 7–11.5). The sponge was placed in eight cases intraluminally, in the other two cases initially intracavitary. No complication occurred.

Conclusions EVT is highly effective for managing acute esophageal perforation within 1 to 3 weeks. Immediate start of EVT to prevent abscess formation and induce defect closure is crucial.