bluuebunny/crossref_metadata_2025 huggingface dataset:
Postoperative consequences of cancer cachexia after head and neck free flap reconstruction
Authors: Jones Alexander Joseph , Davis Kyle Patrick , Novinger Leah J. , Bonetto Andrea , Mantravadi Avinash V. , Sim Michael W. , Yesensky Jessica A. , Moore Michael G.
Published: April 2022

Background

Cachexia is detrimental for patients with head and neck cancer (HNC). However, postoperative consequences of HNC cachexia remain unknown.

Methods

A 2014–2019 retrospective review was performed of adults undergoing aerodigestive HNC resection with free tissue reconstruction. Propensity score matching using inverse probability of treatment weighting (IPTW) of cachectic and control groups was employed to adjust for covariate imbalances followed by binary logistic regression on postoperative outcomes.

Results

Out of 252 total patients, 135 (53.6%) had cancer cachexia. The cohort was predominantly white (94.4%) males (65.1%) aged 61.5 ± 11.5 years with stage III–IV (84.1%) malignancy of the oral cavity (66.3%). After matching cohort pre‐ and intra‐operative covariates using IPTW, cancer cachexia remained a strong, significant predictor of serious National Surgical Quality Improvement Program (NSQIP) complications (OR [95%CI] = 3.84 [1.80–8.21]) and major Clavien‐Dindo complications (OR [95%CI] = 3.00 [1.18–7.60]).

Conclusions

Cancer cachexia is associated with worse HNC free flap reconstruction outcomes.
Commentary on six solutions: Moving forward with measurement in mind
Authors: DeBolt Michaela C. , Oakes Lisa M.
Published: April 2022

In their target article, Byers‐Heinlein, Bergman and Savalei describe the neglected challenge of measurement reliability in infancy research. In this commentary, we elaborate on the problem of measurement reliability and demonstrate the problem it poses when using looking time measures to assess individual differences in infancy. We endorse the solutions Byers‐Heinlein et al. propose to increase measurement reliability. In particular, we encourage the field to develop more reliable measures of individual differences infant looking time.
Induction with MEDA regimen and consolidation with Auto‐HSCT for stage IV NKTCL patients: A prospective multicenter study
Authors: Liu Chuanxu , Ding Hao , Zhu Qi , Liu Peng , Zhu Yang , Wang Lifeng , Ma Yujie , Zhang Wenhao , Tian Shu , Zhang Xiaoyan , Jin Lina , Liu Ligen , Li Zhichao , Hao Siguo , Tao Rong
Published: April 2022

Optimal treatment strategies for natural killer/T‐cell lymphoma (NKTCL) patients with stage IV disease have not been well defined. In this prospective phase 2 study, we evaluated the treatment using MEDA (methotrexate, etoposide, dexamethasone and pegaspargase) as induction chemotherapy and autologous hematopoietic stem cell transplantation (Auto‐HSCT) for consolidation. Patients with stage IV disease without prior L‐asparaginase‐based chemotherapy were eligible. Four cycles of MEDA were administered as induction treatment. Patients with complete response (CR, necessary to have complete metabolic remission of PET/CT, negative plasma EBV‐DNA and negative EBER staining of bone marrow biopsy tissue) were consolidated by Auto‐HSCT. A total of 53 patients were enrolled. The overall response (OR) rate and CR rate after four cycles of MEDA chemotherapy were 75.5% and 56.6%, respectively. Among them, 25 patients underwent Auto‐HSCT. The 4‐year overall survival (OS) rate and progression‐free survival (PFS) rate were 58.0% (95% CI, 43.4%‐70.0%) and 43.4% (95% CI, 29.9%‐56.1%), respectively. Patients who underwent Auto‐HSCT had a 4‐year OS rate of 92.0% (95% CI, 71.6%‐97.9%) and a 4‐year PFS rate of 80.0% (95% CI, 58.4%‐91.1%). Grade 3/4 neutropenia and thrombocytopenia occurred in 28.3% and 17.0% of the patients, respectively. MEDA chemotherapy is an effective induction regimen with reduced grade 3/4 hematological toxicities for stage IV NKTCL. Consolidation with Auto‐HSCT can be considered as a potential approach to improve the long‐term survival of CR patients after induction treatment.
Meat consumption and risk of esophageal and gastric cancer in the Golestan Cohort Study, Iran
Authors: Collatuzzo Giulia , Etemadi Arash , Sotoudeh Masoud , Nikmanesh Arash , Poustchi Hossein , Khoshnia Masoud , Pourshams Akram , Hashemian Maryam , Roshandel Gholamreza , Dawsey Sanford M. , Abnet Christian C. , Kamangar Farin , Brennan Paul , Boffetta Paolo , Malekzadeh Reza
Published: April 2022

Red meat and processed meat are associated with some gastrointestinal cancers. Our study aims to investigate the association of different meat types with esophageal and gastric cancer (EC, GC) in a high‐risk population. The Golestan Cohort Study (GCS) is a population‐based cohort of 50 045 individuals aged 40 to 75 from northeast Iran. Detailed data on different exposures were collected using validated questionnaires. We considered quintiles of meat consumption, using grams and density (g/1000 kcal/day). We calculated intake of red, processed, organ and white meat, as well as total red meat, including the first three. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between meat types and cancer. During 12 years of follow‐up, out of 49 585 participants (57.4% women), 369 developed EC (48.2% women) and 368 developed GC (27.5% women), including 309 esophageal squamous cell, 20 esophageal adenocarcinomas, 216 cardia and 95 non‐cardia GC. No association was found for EC except for red meat among females (HR for one quintile increase 1.13, 95% CI = 1.00‐1.27). The risk of GC increased for intake of total red meat (HR 1.08, 95% CI = 1.00‐1.17) and red meat separately (HR 1.09, 95% CI = 1.00‐1.18). The HR for red meat and non‐cardia GC was 1.23 (95% CI = 1.02‐1.48). No associations were observed for other types of meat. In conclusion, in this high‐risk population red meat intake is associated with GC, but not EC, suggesting a substantial role of this modifiable factor in determining the burden of GC.
CANTO‐RT: Skin toxicities evaluation of a multicentre large prospective cohort of irradiated patients for early‐stage breast cancer
Authors: Allali Sofiane , Carton Matthieu , Sarrade Thomas , Querel Ophélie , Jacquet Alexandra , Rivera Sofia , Ghannam Youssef , Peignaux Karine , Guilbert Philippe , Chara‐Brunaud Claire , Blanchecotte Julien , Pasquier David , Racadot Séverine , Bourgier Céline , Labib Alain , Geffrelot Julien , Benyoucef Ahmed , Paris François , Cottu Paul , André Fabrice , Kirova Youlia
Published: April 2022

Skin damage is the most common and most important toxicity during and after radiation therapy (RT). Its assessment and understanding of the factors influencing its occurrence, is a major issue in the management of patients irradiated for an early breast cancer. CANTO is a prospective clinical cohort study of 10 150 patients with stage I‐III BC treated from 2012 to 2017 in 26 cancer centres. In our study, we used CANTO‐RT, a subcohort of CANTO, including 3480 patients who received RT. We are focus on specific skin toxicities: erythema, fibrosis, telangiectasia and cutaneous pigmentation. The prevalence of toxicities of interest varied over time, so at baseline for early toxicity Month (M) 0‐3‐6, 41.1% of patients had erythema while 24.8% of patients had fibrosis. At M12 and M36, the prevalence of erythema decreased, respectively, while fibrosis remains stable. The prevalence of telangiectasia increases from 1% to 7.1% from M0‐3‐6 to M36. After adjustments, we showed an association between the occurrence of skin erythema and obesity; the type of surgery; the presence of axillary dissection; the use of taxane‐based CT and the 3D vs IMRT irradiation technique. Regarding fibrosis, an association is found, at M0‐3‐6, with age at diagnosis, obesity, tobacco and the use of boost. Only obesity and the type of surgery received by the patient remained statistically significant at M12 and M36. In our study we identified several risk factors for acute and late skin reactions. The use of a boost was mainly related to the occurrence of fibrosis while the use of IMRT‐type technique decreased the occurrence of skin erythema.
Impact of noncoding RNAs on cancer directed immune therapies: Now then and forever
Authors: Roy Roshan Kumar , Yadav Rakhi , Sharma Uttam , Wasson Mishi Kaushal , Sharma Ashok , Tanwar Pranay , Jain Aklank , Prakash Hridayesh
Published: April 2022

Accumulating evidence demonstrates that the host genome's epigenetic modifications are essential for living organisms to adapt to extreme conditions. DNA methylation, covalent modifications of histone and interassociation of noncoding RNAs facilitate the cellular manifestation of epigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, noncoding RNAs (ncRNAs) such as microRNA (miRNA), long noncoding RNA (lncRNA), circular RNA, snoRNA and piRNA are new generation noncoding molecules that influence a variety of cellular processes like immunity, cellular differentiation and tumor development. During tumor development, temporal changes in miRNA/lncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signaling in the host. At the cellular level, this is manifested by the upregulation of inflammasome and inflammatory pathways, which promotes cancer‐related inflammation. Given this, we discuss the potential of lncRNAs, miRNAs, circular RNA, snoRNA and piRNA in regulating inflammation and tumor development in the host.
Predictive value of chromosome 18q11.2‐q12.1 loss for benefit from bevacizumab in metastatic colorectal cancer: A post hoc analysis of the randomized phase III‐trial AGITG‐MAX
Authors: van Dijk Erik , van Werkhoven Erik , Asher Rebecca , Mooi Jennifer K. , Espinoza David , van Essen Hendrik F. , van Tinteren Harm , van Grieken Nicole C. T. , Punt Cornelis J. A. , Tebbutt Niall C. , Ylstra Bauke
Published: April 2022

The VEGF‐A monoclonal antibody bevacizumab is currently recommended for first‐line treatment of all metastatic colorectal cancer (mCRC) patients. Cost‐benefit ratio and side‐effects however necessitate patient selection. A large retrospective yet nonrandomized study showed that patients with loss of chromosome 18q11.2‐q12.1 in the tumor and treated with bevacizumab have 3 months improved median progression‐free (PFS) and overall survival (OS) benefit compared to patients without this loss and/or treatment modality. Implementation for loss of chromosome 18q11.2‐q12.1 as a marker in clinical practice mandates evidence in a randomized controlled trial for bevacizumab. Of the trials with randomization of chemotherapy vs chemotherapy with bevacizumab, the AGITG‐MAX trial was the only one with tumor materials available. Chromosome 18q11.2‐q12.1 copy number status was measured for 256 AGITG‐MAX trial patients and correlated with PFS according to a predefined analysis plan with marker‐treatment interaction as the primary end‐point. Chromosome 18q11.2‐q12.1 losses were detected in 71% of patients (181/256) characteristic for mCRC. Consistent with the nonrandomized study, significant PFS benefit of bevacizumab was observed in patients with chromosome 18q11.2‐q12.1 loss (P = .009), and not in patients without 18q loss (P = .67). Although significance for marker‐treatment interaction was not reached (Pinteraction = .28), hazard ratio and 95% confidence interval of this randomized cohort (HRinteraction = 0.72; 95% CI = 0.39‐1.32) shows striking overlap with the nonrandomized study cohorts (HRinteraction = 0.41; 95% CI = 0.32‐0.8) supported by a nonsignificant Cochrane χ2 test (P = .11) for heterogeneity. We conclude that post hoc analysis of the AGITG‐MAX RCT provides supportive evidence for chromosome 18q11.2‐q12.1 as a predictive marker for bevacizumab in mCRC patients.
Long‐term survival of a patient with refractory advanced adrenocortical carcinoma after combination chemotherapy with paclitaxel and carboplatin plus mitotane
Authors: Kobayakawa Yuki , Hamamoto Shuzo , Kamisawa Hideyuki , Okada Shinsuke , Taguchi Kazumi , Naiki Taku , Okada Atsushi , Tozawa Keiichi , Yasui Takahiro
Published: April 2022

Introduction

The prognosis of patients with unresectable adrenocortical carcinoma is poor. Mitotane is the first‐line treatment for this disease, and etoposide/doxorubicin/cisplatin/mitotane therapy is recommended as first‐line chemotherapy in unresponsive cases. We present a case of long‐term survival following combination chemotherapy with paclitaxel and carboplatin plus mitotane to manage mitotane‐refractory advanced adrenocortical carcinoma.

Case presentation

A 49‐year‐old woman with a left adrenal tumor, lymph node metastasis around the aorta, and multiple liver metastases was treated with mitotane. The disease progressed despite mitotane therapy; thus, combination chemotherapy with paclitaxel and carboplatin plus mitotane was administered for 9 months. Primary adrenal resection was performed after the liver metastasis had completely dissapeared. She has remained alive for 20 years since her initial diagnosis while undergoing mitotane therapy.

Conclusion

In this case, combination chemotherapy with paclitaxel and carboplatin plus mitotane effectively controlled advanced adrenocortical carcinoma.
Distinct Inflammatory Macrophage Populations Sequentially Infiltrate Bone‐to‐Tendon Interface Tissue After Anterior Cruciate Ligament (ACL) Reconstruction Surgery in Mice
Authors: Fujii Takayuki , Wada Susumu , Carballo Camila B. , Bell Richard D. , Morita Wataru , Nakagawa Yusuke , Liu Yake , Chen Daoyun , Pannellini Tania , Sokhi Upneet K. , Deng Xiang‐hua , Park‐Min Kyung Hyung , Rodeo Scott A. , Ivashkiv Lionel B.
Published: April 2022

Macrophages are important for repair of injured tissues, but their role in healing after surgical repair of musculoskeletal tissues is not well understood. We used single‐cell RNA sequencing (RNA‐seq), flow cytometry, and transcriptomics to characterize functional phenotypes of macrophages in a mouse anterior cruciate ligament reconstruction (ACLR) model that involves bone injury followed by a healing phase of bone and fibrovascular interface tissue formation that results in bone‐to‐tendon attachment. We identified a novel “surgery‐induced” highly inflammatory CD9+ IL1+ macrophage population that expresses neutrophil‐related genes, peaks 1 day after surgery, and slowly resolves while transitioning to a more homeostatic phenotype. In contrast, CX3CR1+ CCR2+ macrophages accumulated more slowly and unexpectedly expressed an interferon signature, which can suppress bone formation. Deletion of Ccr2 resulted in an increased amount of bone in the surgical bone tunnel at the tendon interface, suggestive of improved healing. The “surgery‐induced macrophages” identify a new cell type in the early phase of inflammation related to bone injury, which in other tissues is dominated by blood‐derived neutrophils. The complex patterns of macrophage and inflammatory pathway activation after ACLR set the stage for developing therapeutic strategies to target specific cell populations and inflammatory pathways to improve surgical outcomes. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Apparent Diffusion Coefficient MRI Shows Association With Early Progression of Unresectable Intrahepatic Cholangiocarcinoma With Combined Targeted‐Immunotherapy
Authors: Sheng Ruofan , Sun Wei , Huang Xiaoyong , Jin Kaipu , Gao Shanshan , Zeng Mengsu , Wu Dong , Shi Guoming
Published: April 2022

Background

Most intrahepatic cholangiocarcinomas (ICCs) are diagnosed at advanced stage with an extremely poor prognosis. For these patients, combining targeted therapies and immunotherapy may have a promising therapeutic effect, and current Response Evaluation Criteria in Solid Tumors (RECIST) criteria have limited applicability.

Purpose

To investigate the associations between pretreatment MRI features and the efficacy of combined targeted‐immunotherapy by estimating the risk of early progression (EP) in unresectable ICC, with special emphasis on diffusion‐weighted imaging.

Study Type

Retrospective.

Subjects

A total of 43 unresectable ICC patients (24 with EP [disease progression ≤12 months after treatment] and 19 with nonearly progression [NEP, disease progression >12 months]), who received first‐line systemic therapy with lenvatinib plus PD1 antibody combination.

Field Strength/Sequence

The 0‐T scanner, including T1‐ and T2‐weighted imaging, diffusion‐weighted imaging, and dynamic gadopentetate dimeglumine‐enhanced imaging.

Assessment

Clinical characteristics and MR imaging features including apparent diffusion coefficient (ADC), as well as survival analysis of EP were evaluated.

Statistical Tests

Features between EP and NEP groups were compared by univariate analyses and multivariate logistic regression analysis. Diagnostic performance was analyzed by receiver operating characteristic curve. Univariate and multivariate Cox regression models were applied for survival analysis of EP. The progression‐free survival (PFS) rates were estimated using the Kaplan–Meier analysis and compared by the log‐rank test. The significance threshold was set at P < 0.05.

Results

Tumor number, tumor margin, arterial peritumoral enhancement, lymphatic metastasis, and apparent diffusion coefficient (ADC) value were significantly different between EP and NEP groups. At multivariate logistic regression analysis, ADC was the only independent variable associated with EP (odds ratio = 0.012), with an area under the curve of 0.774 (optimal cutoff value was 1.028 × 10−3 mm2/sec). Multivariate Cox regression model proved that ADC value (hazard ratio = 0.140) and ill‐defined margin (hazard ratio = 2.784) were independent risk factors. ICCs with low ADC values showed shorter PFS than those with high values (χ2 = 9.368).

Data Conclusion

Pretreatment MRI features were associated with EP for unresectable ICC treated with combined targeted‐immunotherapy, and decreased ADC value was an independent variable.

Evidence Level

3

Technical Efficacy

Stage 4
Comprehensive role of SARS‐CoV‐2 spike glycoprotein in regulating host signaling pathway
Authors: Banerjee Shuvomoy , Wang Xinyu , Du Shujuan , Zhu Caixia , Jia Yuping , Wang Yuyan , Cai Qiliang
Published: April 2022

Since the outbreak of coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, global public health and the economy have suffered unprecedented damage. Based on the increasing related literature, the characteristics and pathogenic mechanisms of the virus, and epidemiological and clinical features of the disease are being rapidly discovered. The spike glycoprotein (S protein), as a key antigen of SARS‐CoV‐2 for developing vaccines, antibodies, and drug targets, has been shown to play an important role in viral entry, tissue tropism, and pathogenesis. In this review, we summarize the molecular mechanisms of interaction between S protein and host factors, especially receptor‐mediated viral modulation of host signaling pathways, and highlight the progression of potential therapeutic targets, prophylactic and therapeutic agents for prevention and treatment of SARS‐CoV‐2 infection.
Effects of hindlimb suspension on development of proximal and distal femur morphological abnormalities in growing rats
Authors: Ozawa Junya , Kaneguchi Akinori , Ezumi Shun , Maeno Takuma , Iwazawa Jukiya , Minanimoto Kengo , Ikeda Airi
Published: April 2022

Although morphological abnormalities of the femur are known predisposing factors for numerous musculoskeletal disorders, the etiology of these abnormalities is poorly understood. This study aimed to investigate whether femoral morphogenesis is affected by hindlimb suspension (HS) in growing rats. We used 41 four‐week‐old female rats in this study. In the HS groups, rats were suspended from their tails for 2, 4, and 8 weeks. Age‐matched animals were used as controls. We examined morphological indices of the femur using three‐dimensional reconstructed images from X‐ray computed tomography. The femoral neck anteversion angle (AVA) was higher with growth in the experimental groups and did not differ in control groups. The AVAs in the HS groups were larger than controls at any time point. In the control groups, the trochlear angle (TA) was higher, rotating inward with growth, but did not differ in the HS groups. The TAs in the HS groups were smaller and rotated more outward compared with the control groups at any time point. The height ratios of the medial and lateral condyles (MC/LC), an asymmetry index, were larger in the HS groups compared to controls at any time point. There were strong relationships between proximal (AVA) and distal morphologies, such as the TA (Spearman's coefficient [rs] = −0.80, p < 0.001) and MC/LC (rs = 0.79, p < 0.001). Our data suggest that sufficient physical activity in early life may protect against morphological femur abnormalities associated with hip and knee joint diseases.
Interaction of surface topography and taper mismatch on head‐stem modular junction contact mechanics during assembly in modern total hip replacement
Authors: Gustafson Jonathan A. , Mell Steven P. , Levine Brett R. , Pourzal Robin , Lundberg Hannah J.
Published: April 2022

Implant failure due to fretting corrosion at the head‐stem modular junction is an increasing problem in modular total hip arthroplasty. The effect of varying microgroove topography on modular junction contact mechanics has not been well characterized. The aim of this study was to employ a novel, microgrooved finite element (FEA) model of the hip taper interface and assess the role of microgroove geometry and taper mismatch angle on the modular junction mechanics during assembly. A two‐dimensional, axisymmetric FEA model was created using a modern 12/14 taper design of a CoCrMo femoral head taper and Ti6Al4V stem taper. Microgrooves were modeled at the contacting interface of the tapers and varied based on height and spacing measurements obtained from a repository of measured retrievals. Additionally, taper angular mismatch between the head and stem was varied to simulate proximal‐ and distal‐locked engagement. Forty simulations were conducted to parametrically evaluate the effects of microgroove surface topography and angular mismatch on predicted contact area, contact pressure, and equivalent plastic strain. Multiple linear regression analysis was highly significant (p < 0.001; R2 > 0.74) for all outcome variables. The regression analysis identified microgroove geometry on the head taper to have the greatest influence on modular junction contact mechanics. Additionally, there was a significant second order relationship between both peak contact pressure (p < 0.001) and plastic strain (p < 0.001) with taper mismatch angle. These modeling techniques will be used to identify the implant parameters that maximize taper interference strength via large in‐silico parametric studies.
Utilizing advanced spatio‐temporal backgrounds with dynamic test signals for high dynamic range display metrology
Authors: Kunkel Timo , Friedrich Florian
Published: April 2022

Test targets are indispensable for display metrology and in combination with a light measurement device, and they can be used to assess a display's performance. Simple synthetic patterns with static backgrounds are currently the target of choice. However, modern display devices have significantly increased in complexity. With that, using static test sequences is likely not painting the full picture of a display's performance, especially as spatial and temporal complexity can only be addressed rudimentarily. In this paper, we discuss novel assessment approaches using dynamic test targets with spatio‐temporal backgrounds, and how they can be compiled in meaningful test sequences e.g. for automated measurements.
Use of Polyesters in Fused Deposition Modeling for Biomedical Applications
Authors: Grivet‐Brancot Arianna , Boffito Monica , Ciardelli Gianluca
Published: April 2022

In recent years, 3D printing techniques experience a growing interest in several sectors, including the biomedical one. Their main advantage resides in the possibility to obtain complex and personalized structures in a cost‐effective way impossible to achieve with traditional production methods. This is especially true for fused deposition modeling (FDM), one of the most diffused 3D printing methods. The easy customization of the final products’ geometry, composition, and physicochemical properties is particularly interesting for the increasingly personalized approach adopted in modern medicine. Thermoplastic polymers are the preferred choice for FDM applications, and a wide selection of biocompatible and biodegradable materials is available to this aim. Moreover, these polymers can also be easily modified before and after printing to better suit the body environment and the mechanical properties of biological tissues. This review focuses on the use of thermoplastic aliphatic polyesters for FDM applications in the biomedical field. In detail, the use of poly(ε‐caprolactone), poly(lactic acid), poly(lactic‐co‐glycolic acid), poly(hydroxyalkanoate)s, thermoplastic poly(ester urethane)s, and their blends is thoroughly surveyed, with particular attention to their main features, applicability, and workability. The state‐of‐the‐art is presented and current challenges in integrating the additive manufacturing technology in the medical practice are discussed.
Sustainable Synthesis of Non‐Isocyanate Polyurethanes Based on Renewable 2,3‐Butanediol
Authors: Kirchberg Anja , Khabazian Esfahani Masood , Röpert Marie‐Christin , Wilhelm Manfred , Meier Michael A. R.
Published: April 2022

In this work, three different cyclic carbonates are obtained from renewable diols and transformed into carbamates by reacting them with renewable 11‐amino undecanoic acid methyl ester to synthesize non‐isocyanate poly(ester urethane)s in a sustainable manner. A procedure using 2,3‐butanediol (2,3‐BDO) as a renewable starting material to synthesize a cyclic carbonate with dimethyl carbonate (DMC) is introduced, catalyzed by 1,5,7‐triazabicylco[4.4.0]dec‐5‐ene (TBD). Three purification strategies, i.e., column chromatography, extraction, and distillation, are compared regarding their E‐Factors. Propylene glycol (PG) and ethylene glycol (EG) are used as alternative starting materials to broaden the substrate scope and compare material properties, their cyclic carbonates likewise react to carbamates with 11‐amino undecanoic acid methyl ester. All carbamates are then polymerized in a bulk polycondensation reaction, yielding non‐isocyanate polyurethanes (NIPUs), specifically poly (ester urethane)s, with molecular weights (Mn) up to 10 kDa. Complete characterization is reported using differential scanning calorimetric (DSC), size exclusion chromatographic measurements (SEC), 1H‐NMR as well as IR spectroscopy. The rheological properties of the poly(ester urethane)s are investigated in the framework of small amplitude oscillatory shear (SAOS) and uniaxial elongation.
Quantifying dominant bacterial genera detected in metagenomic data from fish eggs and larvae using genus‐specific primers
Authors: Najafpour Babak , Pinto Patricia I. S. , Canario A. V. M. , Power Deborah M.
Published: April 2022

The goal of this study was to design genus‐specific primers for rapid evaluation of the most abundant bacterial genera identified using amplicon‐based sequencing of the 16S rRNA gene in fish‐related samples and surrounding water. Efficient genus‐specific primers were designed for 11 bacterial genera including Alkalimarinus, Colwellia, Enterovibrio, Marinomonas, Massilia, Oleispira, Phaeobacter, Photobacterium, Polarbacerium, Pseudomonas, and Psychrobium. The specificity of the primers was confirmed by the phylogeny of the sequenced polymerase chain reaction (PCR) amplicons that indicated primers were genus‐specific except in the case of Colwellia and Phaeobacter. Copy number of the 16S rRNA gene obtained by quantitative PCR using genus‐specific primers and the relative abundance obtained by 16S rRNA gene sequencing using universal primers were well correlated for the five analyzed abundant bacterial genera. Low correlations between quantitative PCR and 16S rRNA gene sequencing for Pseudomonas were explained by the higher coverage of known Pseudomonas species by the designed genus‐specific primers than the universal primers used in 16S rRNA gene sequencing. The designed genus‐specific primers are proposed as rapid and cost‐effective tools to evaluate the most abundant bacterial genera in fish‐related or potentially other metagenomics samples.
Prodromal X‐Linked Dystonia‐Parkinsonism is Characterized by a Subclinical Motor Phenotype
Authors: Steinhardt Julia , Hanssen Henrike , Heldmann Marcus , Sprenger Andreas , Laabs Björn‐Hergen , Domingo Aloysius , Reyes Charles Jourdan , Prasuhn Jannik , Brand Max , Rosales Raymond , Münte Thomas F. , Klein Christine , Westenberger Ana , Oropilla Jean Q. , Diesta Cid , Brüggemann Norbert
Published: May 2022

Background

Early diagnosis in patients with neurodegenerative disorders is crucial to initiate disease‐modifying therapies at a time point where progressive neurodegeneration can still be modified.

Objectives

The objective of this study was to determine whether motor or non‐motor signs of the disease occur as indicators of a prodromal phase of X‐linked dystonia‐parkinsonism (XDP), a highly‐penetrant monogenic movement disorder with striking basal ganglia pathology.

Methods

In addition to a comprehensive clinical assessment, sensor‐based balance and gait analyses were performed in non‐manifesting mutation carriers (NMCs), healthy controls (HCs), and patients with XDP. Gradient‐boosted trees (GBT) methodology was utilized to classify groups of interest.

Results

There were no clinically overt disease manifestations in the NMCs. Balance analysis, however, revealed a classification accuracy of 90% for the comparison of NMC versus HC. For the gait analysis, the best‐performing GBT‐based model showed a balanced accuracy of 95% (NMC vs. HC; walking at maximum speed). Using a separate analysis of genetic modifiers, several gait parameters correlated strongly with the estimated age at disease onset in the NMC group.

Conclusions

Our study unraveled balance and gait abnormalities in NMCs that preceded the onset of XDP. These findings demonstrate prodromal motor changes among NMCs who will develop XDP with a very high likelihood in the future. Gait abnormalities had a predictive value for the estimated age at onset highlighting the impact of genetic modifiers in personalized treatment in monogenic neurodegenerative disorders. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
LC–MS Characterization and Quantification of Known and Unknown (Poly)phenol Metabolites—Possible Pitfalls and Their Avoidance
Authors: Clifford Michael N. , Kuhnert Nikolai
Published: April 2022

This review focuses on the LC–MS characterization and quantification of dietary (poly)phenols and their metabolites. It draws attention to errors, omissions, and misunderstandings that appear frequently in published papers, and suggests strategies for their avoidance. Aspects covered include the use of authentic standards and surrogate reference materials, the importance of collecting and archiving Total Ion Current MS data, the limitations of using on‐line compilations of accurate mass MS data to assign unknown components when multiple isomers are possible, and the often understated magnitude of person‐to‐person variation that may significantly impact at population level any potential health benefit.
Toward automatic beam angle selection for pencil‐beam scanning proton liver treatments: A deep learning–based approach
Authors: Kaderka Robert , Liu Keng‐Chi , Liu Lawrence , VanderStraeten Reynald , Liu Tyng‐Luh , Lee Kuang‐Min , Tu Yi‐Chin Ethan , MacEwan Iain , Simpson Daniel , Urbanic James , Chang Chang
Published: April 2022

Background

Dose deposition characteristics of proton radiation can be advantageous over photons. Proton treatment planning, however, poses additional challenges for the planners. Proton therapy is usually delivered with only a small number of beam angles, and the quality of a proton treatment plan is largely determined by the beam angles employed. Finding the optimal beam angles for a proton treatment plan requires time and experience, motivating the investigation of automatic beam angle selection methods.

Purpose

A deep learning–based approach to automatic beam angle selection is proposed for the proton pencil‐beam scanning treatment planning of liver lesions.

Methods

We cast beam‐angle selection as a multi‐label classification problem. To account for angular boundary discontinuity, the underlying convolution neural network is trained with the proposed Circular Earth Mover's Distance–based regularization and multi‐label circular–smooth label technique. Furthermore, an analytical algorithm emulating proton treatment planners’ clinical practice is employed in post‐processing to improve the output of the model. Forty‐nine patients that received proton liver treatments between 2017 and 2020 were randomly divided into training (n = 31), validation (n = 7), and test sets (n = 11). AI‐selected beam angles were compared with those angles selected by human planners, and the dosimetric outcome was investigated by creating plans using knowledge‐based treatment planning.

Results

For 7 of the 11 cases in the test set, AI‐selected beam angles agreed with those chosen by human planners to within 20° (median angle difference = 10°; mean = 18.6°). Moreover, out of the total 22 beam angles predicted by the model, 15 (68%) were within 10° of the human‐selected angles. The high correlation in beam angles resulted in comparable dosimetric statistics between proton treatment plans generated using AI‐ and human‐selected angles. For the cases with beam angle differences exceeding 20°, the dosimetric analysis showed similar plan quality although with different emphases on organ‐at‐risk sparing.

Conclusions

This pilot study demonstrated the feasibility of a novel deep learning–based beam angle selection technique. Testing on liver cancer patients showed that the resulting plans were clinically viable with comparable dosimetric quality to those using human‐selected beam angles. In tandem with auto‐contouring and knowledge‐based treatment planning tools, the proposed model could represent a pathway for nearly fully automated treatment planning in proton therapy.
Nutrition risk assessed by Nutritional Risk Screening 2002 is associated with in‐hospital mortality in older patients with COVID‐19
Authors: Can Busra , Senturk Durmus Nurdan , Olgun Yıldızeli Sehnaz , Kocakaya Derya , Ilhan Birkan , Tufan Asli
Published: April 2022

Background

Although numerous studies have been performed to determine predictors of coronavirus disease 2019 (COVID‐19) mortality, studies that address the geriatric age group are limited. The aim of this study was to investigate the utility of the Nutritional Risk Screening 2002 (NRS‐2002) and the Geriatric 8 (G8) screening tools in predicting clinical outcomes in older adults hospitalized with COVID‐19.

Methods

Patients aged ≥60 years who were hospitalized with COVID‐19 in the second wave of the pandemic were included in the study. COVID‐19 infection was demonstrated by a positive real‐time reverse transcriptase–polymerase chain reaction on nasopharyngeal swab or positive radiological findings. Disease severity was determined as defined by the National Institutes of Health. Patient demographics, laboratory values on admission, comorbidities, and medications were recorded. The NRS‐2002 and the G8 screening tools were performed for all patients by the same geriatrician. Primary outcome was in‐hospital mortality.

Results

A total of 121 patients were included. Mean age was 75 ± 9 years, and 51% were female. Mean body mass index was 27 ± 4.5 kg/m2. Sixty‐nine percent of the patients had nutrition risk according to the NRS‐2002. Eighty‐nine percent of the patients had a G8 score ≤14. In‐hospital mortality occurred in 26 (22%) patients. Older age and having nutrition risk as determined by the NRS‐2002 were independently associated with a higher risk of in‐hospital mortality in older patients with COVID‐19.

Conclusion

The NRS‐2002 tool provides rapid assessment for risk stratification in hospitalized older patients with COVID‐19.
Continuous approximation formulas for location problems
Authors: Carlsson John Gunnar , Jones Bo
Published: April 2022

The majority of research in the continuous approximation paradigm has emphasized routing problems, such as the travelling salesman problem and the vehicle routing problem. This article instead focuses on continuous approximation formulas for problems involving location, specifically the ‐medians, ‐dispersion, and generalized minimum spanning tree problems. We contribute bounds for constants that describe the growth rate of the cost of these problems as the number of demand points becomes large, and conduct computational experiments that verify that they provide a good approximation in practice.
Mitochondrial genome variations, mitochondrial‐nuclear compatibility, and their association with metabolic diseases
Authors: Ludwig‐Słomczyńska Agnieszka H. , Rehm Markus
Published: May 2022

Two genomes regulate the energy metabolism of eukaryotic cells: the nuclear genome, which codes for most cellular proteins, and the mitochondrial genome, which, together with the nuclear genome, coregulates cellular bioenergetics. Therefore, mitochondrial genome variations can affect, directly or indirectly, all energy‐dependent cellular processes and shape the metabolic state of the organism. This review provides a current and up‐to‐date overview on how codependent these two genomes are, how they appear to have coevolved, and how variations within the mitochondrial genome might be associated with the manifestation of metabolic diseases. This review summarizes and structures results obtained from epidemiological studies that identified links between mitochondrial haplogroups and individual risks for developing obesity and diabetes. This is complemented by findings on the compatibility of mitochondrial and nuclear genomes and cellular bioenergetic fitness, which have been acquired from well‐controlled studies in conplastic animal models. These elucidate, more mechanistically, how single‐nucleotide variants can influence cellular metabolism and physiology. Overall, it seems that certain mitochondrial genome variations negatively affect mitochondrial‐nuclear compatibility and are statistically linked with the onset of metabolic diseases, whereas, for others, greater uncertainty exists, and additional research into this exciting field is required.
Expression patterns and prognostic relevance of subtype‐specific transcription factors in surgically resected small‐cell lung cancer: an international multicenter study
Authors: Megyesfalvi Zsolt , Barany Nandor , Lantos Andras , Valko Zsuzsanna , Pipek Orsolya , Lang Christian , Schwendenwein Anna , Oberndorfer Felicitas , Paku Sandor , Ferencz Bence , Dezso Katalin , Fillinger Janos , Lohinai Zoltan , Moldvay Judit , Galffy Gabriella , Szeitz Beata , Rezeli Melinda , Rivard Christopher , Hirsch Fred R , Brcic Luka , Popper Helmut , Kern Izidor , Kovacevic Mile , Skarda Jozef , Mittak Marcel , Marko‐Varga Gyorgy , Bogos Krisztina , Renyi‐Vamos Ferenc , Hoda Mir Alireza , Klikovits Thomas , Hoetzenecker Konrad , Schelch Karin , Laszlo Viktoria , Dome Balazs
Published: April 2022

The tissue distribution and prognostic relevance of subtype‐specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small‐cell lung cancer (SCLC). The expression of subtype‐specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype‐specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC‐A (ASCL1‐dominant), SCLC‐AN (combined ASCL1/NEUROD1), SCLC‐N (NEUROD1‐dominant), and SCLC‐P (POU2F3‐dominant), IHC and cluster analyses identified a quadruple‐negative SCLC subtype (SCLC‐QN). No unique YAP1‐subtype was found. The highest overall survival rates were associated with non‐neuroendocrine subtypes (SCLC‐P and SCLC‐QN) and the lowest with neuroendocrine subtypes (SCLC‐A, SCLC‐N, SCLC‐AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard‐of‐care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype‐specific protein abundances. In conclusion, we investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1, and POU2F3 defines SCLC subtypes. No YAP1‐subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines revealed distinct vulnerability profiles defined by transcription regulators. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Incidences and characteristics of primary lung malignancies in childhood in Germany: An analysis of population‐based data from German cancer registries
Authors: Abele Michael , Voggel Sarah , Bremensdorfer Claudia , Spix Claudia , Erdmann Friederike , Kuhlen Michaela , Redlich Antje , Ebinger Martin , Lang Peter , Schneider Dominik T. , Brecht Ines B.
Published: April 2022

Background: Primary lung malignancies are a heterogeneous group of cancers that occur very rarely in childhood. Due to limited knowledge of their epidemiologic and clinical features, these tumors present a challenge to the treating physicians. This study aimed to increase the knowledge about the occurrence of primary lung malignancies in childhood in Germany.

Materials and methods: Pseudonymized data of cases recorded at the German Center for Cancer Registry Data (ZfKD) between 1990 and 2017 were retrieved. Primary lung malignancies were identified using the ICD‐ and ICD‐O classification. Numbers were compared to those reported to the German Childhood Cancer Registry (GCCR). Crude incidence rates were calculated using the ZfKD database.

Results: A total of 168 patients diagnosed with primary lung malignancies in the age below 19 years were identified from the ZfKD. The median age at diagnosis was 13 years. The most common tumor entities were lung carcinoids (n = 49), lung carcinoma (n = 36), and pleuropulmonary blastoma (n = 14). An unexpected accumulation of lung cancer cases was noted in the first year of life without a clearly specified histopathological diagnosis. A substantial discrepancy in the numbers of primary lung malignancies between ZfKD and GCCR was found.

Conclusions: We present population‐based data on the occurrence of primary childhood lung malignancies in Germany, which were more frequent than previously anticipated but likely remained underreported. For better understanding and optimal treatment of these entities, cancer registration needs to be improved through mandatory reporting to the GCCR and regular data sharing between GCCR, population‐based and clinical cancer registries.
Experimental and numerical investigation of high‐velocity impact effects on composite sandwich panel with M‐shaped core reinforced by nano‐SiO2
Authors: Khaledi Himan , Rostamiyan Yasser , Seyyedi Seyyed Masoud
Published: April 2022

This article has experimentally and numerically investigated the high‐velocity impact resistance of the composite sandwich panel with an M‐shaped lattice core reinforced by nano‐SiO2. For this purpose, firstly, a glass fiber resin epoxy sandwich panel has been fabricated in the laboratory. In this regard, the vacuum‐assisted resin transfer molding (VARTM) method has been used to achieve a laminate without any fault. In order to improve the impact resistance of the composite, the nano‐SiO2 were added to the resin epoxy matrix as filler with the ratios of 1%, 2%, and 3% of the composite's total weight. A scanning electron microscope (SEM) has been utilized to observe the microscopic structure of the composites, and it shows an exceptional homogeneous mixture of nano‐SiO2 particles in the resin epoxy matrix. From the experiment results, it was figured out that by adding 1 to 3 wt% of nano‐SiO2 into the composite, the output velocity of the projectile decreases. On the other hand, the results showed that when the projectile collides with the core of the sandwich panel, it remains in the sandwich panel and its output velocity will be zero. However, when the projectile does not completely collide with the core, the output velocity of the projectile will not be zero. In order to validate the results, a finite element analysis (FEA) has been developed to simulate the high‐velocity impact test. Then the experimental data has been compared to numerical simulation and good agreement was observed.
Review on engineering designing of electromagnetic interference shielding materials using additive manufacturing
Authors: Verma Sarika , Dhangar Manish , Mili Medha , Bajpai Harsh , Dwivedi Umesh , Kumari Neelam , Khan Mohammed Akram , Bhargaw Hari Narayan , Hashmi Sayed Azhar Rasheed , Srivastava Avanish Kumar
Published: April 2022

Recently 3D printing or additive manufacturing has been one of the most popular techniques for fabricating material. 3D printing or additive manufacturing has taken over the modern material fabrication industry in a revolutionary manner. The present review focuses on designing electromagnetic interference (EMI) shielding materials by 3D printing. The various raw materials such as polylactic acid (PLA), polypropylene, graphene, carbon nanotube (CNT), multiwalled carbon nanotube (MCNT), and so forth, can be successfully used for making effective EMI shielding performances in different frequency ranges. These raw materials have prepared diverse shapes, dimensions, and compositions to attenuate the incident radiations over the shielding material's surface and ultimately protect the electronic devices. When mixed with carbon nanotubes, PLA has been shown 8–15 dB, 30 dB, and 67 dB EMI SE in different frequency ranges, a material with ABS and CNT have −3 to −16 dB reflection loss in X‐band frequency. Also graphene nanofilm/MWCNT composition has shown EMI SE as high as 43–54 dB in X‐band ranges when printed with poly jet printing. These properties gave a cutting‐edge rivalry to the conventional fabrication method and proved that 3D printing is better when designing innovation for EMI shielding materials