bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatogenesis and hepatocarcinogenesis: Alignment of the main signaling pathways
Authors: Shokouhian Bahare , Aboulkheyr Es Hamidreza , Negahdari Babak , Tamimi Atena , Shahdoust Maryam , Shpichka Anastasia , Timashev Peter , Hassan Moustapha , Vosough Massoud
Published: August 2022

Development is a symphony of cells differentiation in which different signaling pathways are orchestrated at specific times and periods to form mature and functional cells from undifferentiated cells. The similarity of the gene expression profile in malignant and undifferentiated cells is an interesting topic that has been proposed for many years and gave rise to the differentiation‐therapy concept, which appears a rational insight and should be reconsidered. Hepatocellular carcinoma (HCC), as the sixth common cancer and the third leading cause of cancer death worldwide, is one of the health‐threatening complications in communities where hepatotropic viruses are endemic. Sedentary lifestyle and high intake of calories are other risk factors. HCC is a complex condition in which various dimensions must be addressed, including heterogeneity of cells in the tumor mass, high invasiveness, and underlying diseases that limit the treatment options. Under these restrictions, recognizing, and targeting common signaling pathways during liver development and HCC could expedite to a rational therapeutic approach, reprograming malignant cells to well‐differentiated ones in a functional state. Accordingly, in this review, we highlighted the commonalities of signaling pathways in hepatogenesis and hepatocarcinogenesis, and comprised an update on the current status of targeting these pathways in laboratory studies and clinical trials.
Risk factors for liver‐related mortality of patients with hepatitis C virus after sustained virologic response to direct‐acting antiviral agents
Authors: Hattori Nobuhiro , Ikeda Hiroki , Watanabe Tsunamasa , Satta Yosuke , Ehira Takuya , Suzuki Tatsuya , Kiyokawa Hirofumi , Nakahara Kazunari , Takahashi Hideaki , Matsunaga Kotaro , Matsumoto Nobuyuki , Yasuda Hiroshi , Suzuki Michihiro , Itoh Fumio , Tateishi Keisuke
Published: August 2022

Background and Aim

The aim of this study was to identify the factors associated with liver‐related and non‐liver‐related mortality of patients with hepatitis C virus (HCV) after sustained virologic response (SVR) to direct‐acting antiviral agents (DAAs).

Methods

We conducted a retrospective, single‐center cohort study of HCV patients cured by DAAs.

Results

A total of 330 patients with SVR to DAAs were eligible. The median follow‐up period was 3.38 years (inter‐quartile range: 2.03–4.58). The cumulative liver‐related or non‐liver‐related mortality rates at 1, 3, and 5 years were 0.00 or 1.29%, 2.87 or 3.60%, and 5.10 or 9.46, respectively. Among the liver‐related deaths, 9 of the 10 were from liver cancer. Among the non‐liver‐related deaths, the most common cause was malignancy. Through multivariate analysis using the Cox proportional hazard model, diabetes mellitus (DM, hazard ratio 13.1, 95% confidence interval 2.81–61.3) and a history of hepatocellular carcinoma (HCC, 12.8, 2.76–59.2), independently predicted liver‐related death. No variables were associated with non‐liver‐related death.

Conclusion

Our findings suggest that DM and a history of HCC are risk factors for liver‐related mortality of HCV patients cured by DAAs. These results indicate that early management of HCV and HCC surveillance of diabetic patients after SVR are important to increase the chance of survival. Further studies are needed to confirm the association of DM and HCC history with survival.
The emergence, spread and vanishing of a French SARS‐CoV‐2 variant exemplifies the fate of RNA virus epidemics and obeys the Mistigri rule
Authors: Colson Philippe , Gautret Philippe , Delerce Jeremy , Chaudet Hervé , Pontarotti Pierre , Forterre Patrick , Tola Raphael , Bedotto Marielle , Delorme Léa , Bader Wahiba , Levasseur Anthony , Lagier Jean‐Christophe , Million Matthieu , Yahi Nouara , Fantini Jacques , La Scola Bernard , Fournier Pierre‐Edouard , Raoult Didier
Published: August 2022

The nature and dynamics of mutations associated with the emergence, spread, and vanishing of SARS‐CoV‐2 variants causing successive waves are complex. We determined the kinetics of the most common French variant (“Marseille‐4”) for 10 months since its onset in July 2020. Here, we analyzed and classified into subvariants and lineages 7453 genomes obtained by next‐generation sequencing. We identified two subvariants, Marseille‐4A, which contains 22 different lineages of at least 50 genomes, and Marseille‐4B. Their average lifetime was 4.1 ± 1.4 months, during which 4.1 ± 2.6 mutations accumulated. Growth rate was 0.079 ± 0.045, varying from 0.010 to 0.173. Most of the lineages exhibited a bell‐shaped distribution. Several beneficial mutations at unpredicted sites initiated a new outbreak, while the accumulation of other mutations resulted in more viral heterogenicity, increased diversity and vanishing of the lineages. Marseille‐4B emerged when the other Marseille‐4 lineages vanished. Its ORF8 gene was knocked out by a stop codon, as reported in SARS‐CoV‐2 of mink and in the Alpha variant. This subvariant was associated with increased hospitalization and death rates, suggesting that ORF8 is a nonvirulence gene. We speculate that the observed heterogenicity of a lineage may predict the end of the outbreak.
Therapeutic effects of MSCs, genetically modified MSCs, and NFĸB‐inhibitor on chronic inflammatory osteolysis in aged mice
Authors: Kushioka Junichi , Toya Masakazu , Shen Huaishuang , Hirata Hirohito , Zhang Ning , Huang Ejun , Tsubosaka Masanori , Gao Qi , Teissier Victoria , Li Xueping , Utsunomiya Takeshi , Goodman Stuart B.
Published: August 2022

The number of total joint replacements is increasing, especially in elderly patients, and so too are implant‐related complications such as prosthesis loosening. Wear particles from the prosthesis induce a chronic inflammatory reaction and subsequent osteolysis, leading to the need for revision surgery. This study investigated the therapeutic effect of NF‐ĸB decoy oligodeoxynucleotides (ODN), mesenchymal stem cells (MSCs), and genetically‐modified NF‐ĸB sensing interleukin‐4 over‐secreting MSCs (IL4‐MSCs) on chronic inflammation in aged mice. The model was generated by continuous infusion of contaminated polyethylene particles into the intramedullary space of the distal femur of aged mice (15−17 months old) for 6 weeks. Local delivery of ODN showed increased bone mineral density (BMD), decreased osteoclast‐like cells, increased alkaline phosphatase (ALP)‐positive area, and increased M2/M1 macrophage ratio. Local injection of MSCs and IL4‐MSCs significantly decreased osteoclast‐like cells and increased the M2/M1 ratio, with a greater trend for IL4‐MSCs than MSCs. MSCs significantly increased ALP‐positive area and BMD values compared with the control. The IL4‐MSCs demonstrated higher values for both ALP‐positive area and BMD. These findings demonstrated the therapeutic effects of ODN, MSCs, and IL4‐MSCs on chronic inflammatory osteolysis in aged mice. The two MSC‐based therapies were more effective than ODN in increasing the M2/M1 macrophage ratio, reducing bone resorption, and increasing bone formation. Specifically, MSCs were more effective in increasing bone formation, and IL4‐MSCs were more effective in mitigating inflammation. This study suggests potential therapeutic strategies for treating wear particle‐associated inflammatory osteolysis after arthroplasty in the elderly.
Botulinum neurotoxin type A improves vasti muscle balance, patellar tracking, and pain in patients with chronic patellofemoral pain
Authors: Pal Saikat , Choi Jang‐Hwan , Delp Scott L. , Fredericson Michael
Published: August 2022

The purpose of this study was to determine the effects of botulinum neurotoxin type A (BoNT‐A) on vastus lateralis:vastus medialis (VL:VM) muscle balance, patellar tracking, and pain in patients with chronic patellofemoral (PF) pain. We recruited 13 participants (9 females, 4 males) with recalcitrant PF pain who underwent ultrasound‐guided BoNT‐A injections into the distal third of the VL muscle, followed by a 6‐week home exercise program to strengthen their VM muscle. We imaged the participants in a C‐arm computed tomography (CT) scanner before and after the intervention. We calculated VL:VM ratios from CT images from a supine, nonweight‐bearing condition. We obtained patellar tilt and bisect offset values from CT images from an upright, weight‐bearing condition. We recorded functional pain scores before, immediately after, and 2–4 years after the intervention. We classified the participants into normal tracking and maltracking groups based on their patellar tilt and bisect offset values. BoNT‐A with home exercise reduced VL:VM ratio (18%; p < 0.001), patellar tilt (19%; p = 0.020), and bisect offset (5%; p = 0.025). Four participants classified as maltrackers before the intervention transitioned to normal tracking after the intervention. Functional pain scores improved immediately after the intervention (13%, p < 0.001) and remained improved at 2‐year follow‐up (12%, p = 0.011). Statement of Clinical Significance: This study provides new evidence in support of BoNT‐A for treatment of PF pain. Classification of patients under weight‐bearing conditions may identify individuals who will most benefit from a BoNT‐A treatment.
D‐mannose alleviated alveolar bone loss in mice with experimental periodontitis via regulating the anti‐inflammatory effect of amino acids
Authors: Yang Hua , Han Nannan , Luo Zhenhua , Xu Junji , Guo Lijia , Liu Yi
Published: August 2022

Background

Periodontitis is a chronic infectious disease caused by dysbiosis of oral microbiota, ultimately leading to periodontal alveolar bone loss. The oral subgingival microbiome, a key role in periodontitis pathogenesis, could alter the composition of gut microbiomes resulting in intestinal microbiota disorder. D‐mannose plays an important role in glucose metabolism; whether it is beneficial to prevention and treatment of periodontitis and the regulation of oral and intestinal microbiota changes is still unknown.

Methods

To explore the effect of D‐mannose, we established experimental periodontitis models in mice and then treated with supplementation of D‐mannose in drinking water or gavage to examine the extent of periodontal bone loss using methylene blue staining. Moreover, the oral and fecal samples of mice were collected for 16S rRNA deep sequencing to analyze the changes of oral and gut microbiota after 14 days. Furthermore, amino acid content assays were used to test the concentration of amino acid of gingival tissues and intestinal tissues.

Results

We found that D‐mannose could alleviate periodontal bone loss whether in the manner of drinking water or gavage. 16S rRNA results revealed that the abundance of Firmicutes changed significantly in oral samples, while Firmicutes and Akkermansia muciniphila were dominated in gut microbiota. In addition, we demonstrated that D‐mannose inhibited inflammation and alleviated alveolar bone loss in periodontitis via regulating amino acid metabolism of oral and gut microbiomes.

Conclusion

Our findings provided insight into the mechanism underlying the abilities of D‐mannose in improving periodontitis treatment, suggesting that D‐mannose has potential application in the dental clinic.
Large‐scale mass movements recorded in the sediments of Lake Hallstatt (Austria)–evidence for recurrent natural hazards at a UNESCO World Heritage site
Authors: Lauterbach Stefan , Strasser Michael , Kowarik Kerstin , Reschreiter Hans , Mandl Gerhard W. , Spötl Christoph , Plessen Birgit , Brauer Achim
Published: August 2022

The Bronze to Iron Age underground salt mining complex of Hallstatt (Austria) is widely recognised for its cultural importance and wealth of archaeological artefacts. However, while the daily life in the salt mines is archaeologically well documented and environmental effects of the mining activity have been investigated recently, the impact of natural hazards on the prehistoric mining community is still poorly understood. For instance, while it is well established that the prehistoric underground mines have repeatedly been destroyed by large‐scale mass movements, only little is known about the characteristics and extent of these events as well as about mass‐movement recurrence during more recent times. To shed light on past mass‐movement activity in the vicinity of the Hallstatt salt mines, we investigated sediment cores from adjacent Lake Hallstatt. Within the regular lake sediments we identified three large‐scale event deposits, which are interpreted to originate from spontaneous or seismically induced mass movements in the mid‐19th and late 9th century ce and the mid‐4th century bce. While the age of the latter event is in good agreement with the abandonment of the famous Iron Age cemetery at Hallstatt, the younger events indicate that large‐scale mass movements also occurred repeatedly during the Common Era.
Identifying and managing problematic trials: A research integrity assessment tool for randomized controlled trials in evidence synthesis
Authors: Weibel Stephanie , Popp Maria , Reis Stefanie , Skoetz Nicole , Garner Paul , Sydenham Emma
Published: August 2022

Evidence synthesis findings depend on the assumption that the included studies follow good clinical practice and results are not fabricated or false. Studies which are problematic due to scientific misconduct, poor research practice, or honest error may distort evidence synthesis findings. Authors of evidence synthesis need transparent mechanisms to identify and manage problematic studies to avoid misleading findings. As evidence synthesis authors of the Cochrane COVID‐19 review on ivermectin, we identified many problematic studies in terms of research integrity and regulatory compliance. Through iterative discussion, we developed a research integrity assessment (RIA) tool for randomized controlled trials for the update of this Cochrane review. In this paper, we explain the rationale and application of the RIA tool in this case study. RIA assesses six study criteria: study retraction, prospective trial registration, adequate ethics approval, author group, plausibility of methods (e.g., randomization), and plausibility of study results. RIA was used in the Cochrane review as part of the eligibility check during screening of potentially eligible studies. Problematic studies were excluded and studies with open questions were held in awaiting classification until clarified. RIA decisions were made independently by two authors and reported transparently. Using the RIA tool resulted in the exclusion of >40% of studies in the first update of the review. RIA is a complementary tool prior to assessing “Risk of Bias” aiming to establish the integrity and authenticity of studies. RIA provides a platform for urgent development of a standard approach to identifying and managing problematic studies.
Polysaccharides from steam‐processed Polygonatum cyrtonema Hua protect against d‐galactose‐induced oxidative damage in mice by activation of Nrf2/HO‐1 signaling
Authors: Teng Huanhuan , Zhang Yi , Jin Chuanshan , Wang Tongsheng , Huang Shengzhuo , Li Lei , Xie Songzi , Wu Deling , Xu Fengqing
Published: August 2022

BACKGROUND

Polygonatum cyrtonema Hua is cultivated for its edible and medical value. The steam‐processed rhizome of P. cyrtonema is the main form for daily consumption and it has been used traditionally in tonics for treating various age‐related disorders. The aim of our study was to compare the physicochemical properties and antioxidant activity of polysaccharides respectively extracted from crude P. Cyrtonema (PCPC), and steam‐processed P. cyrtonema (PCPS), and to explore a possible underlying antioxidant mechanism.

RESULTS

The PCPC with a molecular weight of 4.35 × 103 Da mainly consisted of fructose and trace amounts of glucose, whereas PCPS with 4.24 × 104 Da was composed of fructose, arabinose, glucose, xylose, mannose, galacturonic acid and glucuronic acid. The PCPC had a triple‐helical conformation whereas PCPS was a random coil. Both exhibited free radicals‐ scavenging activity in vitro. In a mouse model of oxidative damage, PCPC or PCPS treatment significantly reversed histopathological alterations, reactive oxygen species (ROS) accumulation and the reduction of antioxidant enzyme activity. They both also promoted Nrf2 nuclear transport by decreasing Keap‐1 expression and increasing HO‐1 expression. Both in vitro and in vivo, PCPS exhibited more potent antioxidant activity than PCPC.

CONCLUSION

Overall, the results suggest that PCPS has a stronger effect on the prevention of oxidative damage by activating Nrf2/HO‐1 antioxidant signaling. This study demonstrates the role of steam‐processed P. cyrtonema rhizome and provides valuable perspective for PCPS as a functional agent. © 2022 Society of Chemical Industry.
Utilization of lymph node evaluation at hysterectomy for cervical carcinoma in situ
Authors: Matsuo Koji , Tavakoli Amin , Donovan Kelly M. , Mandelbaum Rachel S. , Klar Maximilian , Roman Lynda D. , Wright Jason D.
Published: August 2022

Background and Objectives

This study examined the utilization and characteristics of lymph node evaluation at hysterectomy for carcinoma in situ of the uterine cervix.

Methods

This retrospective cohort study queried the Healthcare Cost and Utilization Project's National Inpatient Sample, evaluating 7395 patients with cervical carcinoma in situ who underwent hysterectomy from 2016 to 2019. A multivariable binary logistic regression model was fitted to identify independent characteristics related to lymph node evaluation. A classification‐tree was constructed with recursive partitioning analysis to examine utilization patterns of lymph node evaluation.

Results

Lymph node evaluation at hysterectomy was performed in 4.6%. In amultivariable analysis, older age, higher income, use of robotic‐assisted hysterectomy, and surgery at large bed capacity or urban teaching centers in the northeast US region were associated with increased likelihood of lymph node evaluation (all, p < 0.05). Of those independent factors, robotic‐assisted surgery exhibited the largest effect size (adjusted odds ratio 3.23, 95% confidence interval 2.54–4.10). Utilization pattern analysis identified nine unique characteristics, of which robotic‐assisted surgery was the primary indicator for cohort allocation (12.4% vs. 3.2%, p < 0.001). The difference between the lowest–highest patterns was 33.3% (range, 0%–33.3%).

Conclusion

Lymph node evaluation was rarely performed for cervical carcinoma in situ overall and robotic surgery was associated with increased utilization of lymph node evaluation.
Limited‐stage small cell carcinoma of the esophagus treated with curative esophagectomy: A multicenter retrospective cohort study
Authors: Gu Yi‐Min , Yang Yu‐Shang , Shi Gui‐Dong , Yan Cheng‐Yi , Shang Qi‐Xin , Zhang Han‐Lu , Wang Wen‐Ping , Yuan Yong , Chen Long‐Qi
Published: August 2022

Background

This study aimed to investigate the efficacy of surgery in the treatment of small cell carcinoma of the esophagus (SCCE) and explore potential prognostic factors.

Methods

We screened patients with SCCE who underwent esophagectomy from 2010 to 2018 at three institutes. Differences in survival were analyzed using the Kaplan–Meier method and log–rank test. The prognostic factors were identified using univariate and multivariate analyses.

Results

A total of 69 patients were included. Multivariate analysis showed that TNM stage (hazard ratio [HR]: 4.10, 95% confidence interval [CI]: 1.57–10.75, p = 0.004) and adjuvant therapy (HR: 0.28, 95% CI: 0.16–0.51, p < 0.001) were independent prognostic factors. Stage I, stage IIA, and stage IIB disease were merged into the surgery response disease (SRD), whereas stage III disease into the surgery nonresponse disease (SNRD). The SRD group had significantly improved survival compared to the SNRD group (HR: 0.33, 95% CI: 0.19–0.58, p < 0.001). In addition, adjuvant therapy increased survival benefit in the SNRD group (p < 0.001) but not in the SRD group (p = 0.061).

Conclusions

Surgery alone appears to be adequate for disease control in the SRD group, whereas multimodality therapy was associated with improved survival in the SNRD group.
Robotic versus laparoscopic abdominoperineal resections for low rectal cancer: A single‐center randomized controlled trial
Authors: Feng Qingyang , Tang Wentao , Zhang Zhiyuan , Wei Ye , Ren Li , Chang Wenju , Zhu Dexiang , Liang Fei , He Guodong , Xu Jianmin
Published: August 2022

Background and Objectives

Robotic surgery for rectal cancer is gaining popularity, but persuasive evidence on reducing surgical trauma is still lacking. This study compared robotic and laparoscopic abdominoperineal resections (APRs) for the risk of postoperative complications in low rectal cancer.

Methods

Between December 2013 and 2016, patients with rectal cancer ≤5 cm from anal verge, cT1‐T3 N0‐1, or ycT1‐T3 Nx stage, and no distant metastases were enrolled in a single‐center, randomized, controlled trial. Eligible patients were randomly allocated to robotic or laparoscopic APRs at 1:1 ratio. The primary outcome was 30‐day postoperative complication rate (Clavien−Dindo grade II or higher) of the intent‐to‐treat population. The trial registration number is NCT01985698 (http://www.clinicaltrials.gov).

Results

Totally 347 eligible patients were enrolled: 174 in robotic and 173 in laparoscopic group. Robotic APRs significantly reduced postoperative complication rate (13.2% vs. 23.7%, p = 0.013), also reduced open conversion rate (0% vs. 2.9%, p = 0.030), intraoperative hemorrhage (median, 100 vs. 130 ml; p < 0.001), 30‐day readmission rate (2.3% vs. 6.9%; p = 0.044), postoperative hospital stay (median, 5.0 vs. 7.0 days; p < 0.001), and improved urinary and sexual function. No significant difference was observed in long‐term oncological outcomes.

Conclusions

Compared with laparoscopic APRs, robotic APRs significantly reduced surgical trauma and promoted postoperative recovery.
Intraoperative Ultrasound in the Management of Placenta Accreta Spectrum: Waste of Time or Valuable Step
Authors: Nassar Malek , Abdallah Wael , Atallah David
Published: August 2022

Placenta accreta spectrum (PAS) is increasing worldwide paralleling the rising surge of the cesarean section rate. It is well known that sonographic screening for PAS in the second trimester in high‐risk patients can predict and reduce major intraoperative hemorrhage during a cesarean hysterectomy. We report the importance of intraoperative ultrasound in the management PAS disorders. It has a crucial role in the reassessment of the placenta location and invasion, reconsidering the cesarean hysterectomy, localization of the hysterotomy, the bladder dissection, and in the conservative treatment. Workshops and hands‐on training in intraoperative ultrasound among surgeons must be supported.
Evaluation of liver stiffness measurement–based scores in liver transplantation recipients
Authors: Arshad Tamoore , Bhati Chandra S. , Bui Anh T. , Tseng Michael , Vainer Dylan , Miller Austin , Evans Marie‐Claire , Syed Taseen , Patel Vaishali , Idowu Michael O. , Muthiah Mark , Siddiqui Mohammad Shadab
Published: August 2022

Combining bioclinical parameters with liver stiffness measurement (LSM) has improved the diagnostic performance of vibration‐controlled transient elastography (VCTE) for detection of advanced fibrosis in patients with chronic liver disease. However, this approach has not yet been tested in liver transplantation (LT) recipients. Thus, the aim of this study was to evaluate the diagnostic performance of combining LSM‐based scores with LSM alone for the detection of advanced fibrosis in LT recipients. Adult LT recipients with a liver biopsy, VCTE, and clinical data necessary to construct LSM‐based fibrosis models (FibroScan‐AST [FAST], AGILE‐3+, and AGILE‐4) were included (n = 132). The diagnostic statistics for advanced fibrosis (fibrosis stage 0–2 vs. 3–4) were determined by optimal cut‐off using the Youden index. The area under the receiver operating characteristic curve (AUROC) for LSM was 0.94 (95% confidence interval [95% CI], 0.89–0.99), FAST was 0.65 (95% CI, 0.50–0.79), AGILE‐3+ was 0.90 (95% CI, 0.83–0.97), and AGILE‐4 was 0.90 (95% CI, 0.83–0.97). No statistically significant differences were noted between the AUROC of LSM versus LSM‐based scores. The false‐positive rates for AGILE‐3+ and AGILE‐4 were 14.5% and 11.8% compared with 8.3% for LSM alone. The false‐positive rates in LSM‐based scores were higher among patients with diabetes mellitus, higher AST levels, and lower platelet counts. The LSM‐based scores did not improve the diagnostic performance of LSM alone in LT recipients for the detection of advanced fibrosis. This lack of improvement in diagnostic performance results from the impact of immunosuppression on bioclinical profile and underscores the importance of developing LSM‐based scores that are specific to LT patients.
Consumer reactions to AI design: Exploring consumer willingness to pay for AI‐designed products
Authors: Zhang Hao , Bai Xiaofei , Ma Zengguang
Published: August 2022

Companies are increasingly using artificial intelligence (AI) technology to generate promising concepts for new products which are then marketed to consumers as “AI‐designed.” Drawing on four studies and follow‐up studies, this paper explores consumer perceptions of AI design. Based on the information gap model, the studies determine that, compared with professional‐designed products, consumers are more willing to pay for products designed by AI, in which process curiosity plays an intermediary role (Study 1). Crucially, this research also predicts the boundary conditions for the positive effects of AI design. High levels of consumer knowledge lead to an attenuation in consumer curiosity regarding AI design, thereby decreasing the willingness to pay (Study 2), while the product type also has a moderating effect on the influence of the product design sources. Consumers are more willing to pay for utilitarian products designed by AI than hedonic products (Study 3). In addition, we reverify that consumers prefer AI‐designed products through a field study (Study 4). Finally, the research sheds light on how to utilize AI to promote the success of new product innovation from a marketing perspective, providing important theoretical knowledge and actionable managerial implications for future research.
Diffusion Magnetic Resonance Imaging Microstructural Abnormalities in Multiple System Atrophy: A Comprehensive Review
Authors: Pasquini Jacopo , Firbank Michael J. , Ceravolo Roberto , Silani Vincenzo , Pavese Nicola
Published: August 2022

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by autonomic failure, ataxia, and/or parkinsonism. Its prominent pathological alterations can be investigated using diffusion magnetic resonance imaging (dMRI), a technique that exploits the characteristics of water random motion inside brain tissue. The aim of this report was to review currently available literature on the application of dMRI in MSA and to describe microstructural abnormalities, diagnostic applications, and pathophysiological correlates. Sixty‐four published studies involving microstructural investigation using dMRI in MSA were included. Widespread microstructural abnormalities of white matter were described, especially in the middle cerebellar peduncle, corticospinal tract, and hemispheric fibers. Gray matter degeneration was identified as well, with diffuse involvement of subcortical structures, especially in the putamina. Diagnostic applications of dMRI were mostly explored for the differential diagnosis between MSA parkinsonism and Parkinson's disease. Recently, machine learning algorithms for image processing and disease classification have demonstrated high diagnostic accuracy, showing potential for translation into clinical practice. To a lesser extent, clinical correlates of microstructural abnormalities have also been investigated, and abnormalities related to motor, ocular, and cognitive impairments were described. dMRI in MSA has contributed to in vivo identification of known pathological abnormalities. Translation into clinical practice of the latest advancements for the differential diagnosis between MSA and other forms of parkinsonism seems feasible. Current limitations involve the possibility of correctly diagnosing MSA in the very early stages, when the clinical diagnosis is most uncertain. Furthermore, pathophysiological correlates of microstructural abnormalities remain understudied. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Specific Gait Changes in Prodromal Hereditary Spastic Paraplegia Type 4: preSPG4 Study
Authors: Laßmann Christian , Ilg Winfried , Schneider Marc , Völker Maximilian , Haeufle Daniel F.B. , Schüle Rebecca , Giese Martin , Synofzik Matthis , Schöls Ludger , Rattay Tim W.
Published: August 2022

Background

In hereditary spastic paraplegia type 4 (SPG4), subclinical gait changes might occur years before patients realize gait disturbances. The prodromal phase of neurodegenerative disease is of particular interest to halt disease progression by future interventions before impairment has manifested.

Objective

The objective of this study was to identify specific movement abnormalities before the manifestation of gait impairment and quantify disease progression in the prodromal phase.

Methods

Seventy subjects participated in gait assessment, including 30 prodromal SPAST pathogenic variant carriers, 17 patients with mild‐to‐moderate manifest SPG4, and 23 healthy control subjects. An infrared‐camera‐based motion capture system assessed gait to analyze features such as range of motion and continuous angle trajectories. Those features were correlated with disease severity as assessed by the Spastic Paraplegia Rating Scale, neurofilament light chain as a fluid biomarker indicating neurodegeneration, and motor‐evoked potentials.

Results

Compared with healthy control subjects, we found an altered gait pattern in prodromal pathogenic variant carriers during the swing phase in the segmental angle of the foot (Dunn's post hoc test, q = 3.1) and heel ground clearance (q = 2.8). Furthermore, range of motion of segmental angle was reduced for the foot (q = 3.3). These changes occurred in prodromal pathogenic variant carriers without quantified leg spasticity in clinical examination. Gait features correlated with neurofilament light chain levels, central motor conduction times of motor‐evoked potentials, and Spastic Paraplegia Rating Scale score.

Conclusions

Gait analysis can quantify changes in prodromal and mild‐to‐moderate manifest SPG4 patients. Thus, gait features constitute promising motor biomarkers characterizing the subclinical progression of spastic gait and might help to evaluate interventions in early disease stages. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Technical note: Characterization of novel iterative reconstructed cone beam CT images for dose tracking and adaptive radiotherapy on L‐shape linacs
Authors: Lim Rebecca , Penoncello Gregory P. , Hobbis Dean , Harrington Daniel P. , Rong Yi
Published: August 2022

Background

Cone‐beam computed tomography (CBCT) allows for patient setup and positioning, and potentially dose verification or adaptive replanning prior to each treatment delivery. Poor CBCT image quality due to scatter artifacts and patient motion has been a major limiting factor. A new image reconstruction algorithm was recently clinically implemented for improving image quality through iterative reconstruction (iCBCT).

Purpose

This study aims to characterize iCBCT image quality, establish image value (HU)‐to‐relative electron density (RED) calibration curves for dose calculation, and assess the dosimetric accuracy for different anatomical sites.

Material and methods

Both conventional CBCT and iCBCT scans were acquired from a Varian TrueBeam On‐Board Imager system. A Catphan 604 phantom was scanned to compare image quality between the traditional Feldkamp–Davis–Kress (FDK) and novel iterative reconstruction techniques. Computerized Imaging Reference Systems (CIRS) electron density phantom was used to construct site‐specific HU‐RED curves corresponding to various scan settings. The CIRS Dynamic Thorax phantom, Rando pelvis phantom, and BrainLab head phantom were used for assessing dosimetric accuracy calculated on iCBCT images, compared to that on traditional FDK‐based CBCT images. All phantoms were scanned on a computed tomography (CT) to obtain baseline HU values for comparison.

Results

Test results obtained from Catphan showed statistically significant improvement with iCBCT, compared to FDK CBCT. Average HU differences from the baseline CT values were improved to within ±30 HU for iCBCT, compared to FDK CBCT for phantom studies. Dose calculated on iCBCT for both phantoms and patient cases directly using baseline HU‐RED calibration from CT showed 0.5%–2.0% accuracy from the baseline dose calculated on CT, which is comparable to doses calculated using site‐specific HU‐RED calibration curves.

Conclusion

iCBCT provides improved image quality, improved HU accuracy compared to CT baseline, and has potential to provide online dose verification as part of the adaptive radiotherapy workflow directly using the baseline HU‐RED calibration curve from CT.
Self‐gated, dynamic contrast‐enhanced magnetic resonance imaging with compressed‐sensing reconstruction for evaluating endothelial permeability in the aortic root of atherosclerotic mice
Authors: Calcagno Claudia , David John A. , Motaal Abdallah G. , Coolen Bram F. , Beldman Thijs , Corbin Alexandra , Kak Arnav , Ramachandran Sarayu , Pruzan Alison , Sridhar Arthi , Soler Raphael , Faries Christopher M. , Fayad Zahi A. , Mulder Willem J. M. , Strijkers Gustav J.
Published: August 2022

High‐risk atherosclerotic plaques are characterized by active inflammation and abundant leaky microvessels. We present a self‐gated, dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) acquisition with compressed sensing reconstruction and apply it to assess longitudinal changes in endothelial permeability in the aortic root of Apoe−/− atherosclerotic mice during natural disease progression. Twenty‐four, 8‐week‐old, female Apoe−/− mice were divided into four groups (n = 6 each) and imaged with self‐gated DCE‐MRI at 4, 8, 12, and 16 weeks after high‐fat diet initiation, and then euthanized for CD68 immunohistochemistry for macrophages. Eight additional mice were kept on a high‐fat diet and imaged longitudinally at the same time points. Aortic‐root pseudo‐concentration curves were analyzed using a validated piecewise linear model. Contrast agent wash‐in and washout slopes (b1 and b2) were measured as surrogates of aortic root endothelial permeability and compared with macrophage density by immunohistochemistry. b2, indicating contrast agent washout, was significantly higher in mice kept on an high‐fat diet for longer periods of time (p = 0.03). Group comparison revealed significant differences between mice on a high‐fat diet for 4 versus 16 weeks (p = 0.03). Macrophage density also significantly increased with diet duration (p = 0.009). Spearman correlation between b2 from DCE‐MRI and macrophage density indicated a weak relationship between the two parameters (r = 0.28, p = 0.20). Validated piecewise linear modeling of the DCE‐MRI data showed that the aortic root contrast agent washout rate is significantly different during disease progression. Further development of this technique from a single‐slice to a 3D acquisition may enable better investigation of the relationship between in vivo imaging of endothelial permeability and atherosclerotic plaques' genetic, molecular, and cellular makeup in this important model of disease.
Civil society organizations and the prevention of mass atrocities: Perspectives from south Sudan
Authors: Appe Susan , Rubaii Nadia , Whigham Kerry
Published: August 2022

Nowhere is the role of civil society organizations (CSOs) in development and democratization more critical than in countries at high risk of mass atrocities. In this article, we examine the actual and potential role of development CSOs in the prevention of mass atrocities based on an analysis of 302 CSOs in South Sudan. The article examines if and how service‐providing CSOs frame their work as contributing to the prevention of mass atrocities. The article seeks to understand how these CSOs deliver services and articulate their work regarding the prevention of large‐scale identity‐based violence. We aim to explore the degree to which organizations describe atrocity prevention as an intentional part of democratization efforts. The article is situated within the larger debates about the service delivery and civil society functions of CSOs. Specifically, we ask: To what extent do development CSOs articulate a contribution to the prevention of mass atrocities? We posit that the service delivery and civil society functions can be better achieved by giving deliberate attention to an atrocity prevention perspective.
A nomogram model to predict prognosis of patients with hepatoblastoma
Authors: Ke Meng , Zhou Yan , Chang‐zhen Yang , Li Long , Diao Mei
Published: August 2022

Background

Hepatoblastomas (HBs) are malignant liver tumors that most commonly develop in pediatric patients. Microvascular invasion may be a prognosis factor for patients with HBs. This study aimed to construct a model to predict the survival outcome in HBs.

Methods

We retrospectively analyzed the clinical data of 311 patients with HBs who underwent surgical resection at our institution between June 2014 and August 2021. First, patients were divided into two groups: those who had pathologic microvascular invasion (n = 146) and those who did not (n = 165). Propensity score‐matched (PSM) analysis was carried out between the two groups. The preoperative parameters and overall survival (OS) rate were compared between the two groups. Second, all 311 patients were randomly divided into the training and validation cohort in a ratio of 4:1. A nomogram was created in the training cohort to visualize the prediction of OS. Moreover, the validation cohort was used for validation.

Results

Multivariate analysis suggested that age, histology type, microvascular invasion, multifocality, distant metastasis, and macrovascular involvement are independent prognostic factors for HBs. The nomogram showed good predictive ability in the training and validation cohorts with a C‐index of 0.878 (95% CI, 0.831‐0.925) and 0.847 (95% CI, 0.757‐0.937), respectively. The calibration curve indicated good agreement between the prediction and observation for one‐, two‐, and three‐year OS probabilities.

Conclusion

By combining preoperative imaging results and other clinical data, we established a nomogram to predict OS probability for patients with HB, which could be a potential tool to guide personalized treatment.
Copper Nanoclusters Loaded on SA/PVA Composite Films for Sensitive Detection of Trace Water in Organic Solvent
Authors: Wei Wei , Ding Juan , Hou Haoting , Miao Xirui , Wang Mao , Pang Shujie , Yang Xudong
Published: August 2022

Copper nanoclusters (CuNCs), a new type of fluorescent material, have attracted extensive attention due to their excellent fluorescence properties and stability. In this paper, orange–red organic fluorescent CuNCs are prepared using reduced glutathione both as a template and reducing agent. CuNCs are then doped into a polymer matrix of alginate and polyvinyl alcohol using the aggregation‐induced emission enhancement effect to produce a kind of easy to use fluorescent composite films. The fluorescent composite films can realize the specific detection of trace water in the organic environment, and the detection limit can reach 0.0025% (volume ratio). Compared with the pure exposed CuNCs, the fluorescence intensity is greatly improved, and more importantly, the fluorescent composite films can be used repeatedly, saving resources and environmental protection.
Analysis of protein structures containing HEPES and MES molecules
Authors: Macnar Joanna Magdalena , Brzezinski Dariusz , Chruszcz Maksymilian , Gront Dominik
Published: August 2022

X‐ray crystallography is the main experimental method behind ligand–macromolecule complexes found in the Protein Data Bank (PDB). Applying bioinformatics methods to such structural data can fuel drug discovery, albeit under the condition that the information is correct. Regrettably, a small number of structures in the PDB are of suboptimal quality due to incorrectly identified and modeled ligands in protein–ligand complexes. In this paper, we combine a theoretical‐graph approach, nuclear density estimates, bioinformatics methods, and prior chemical knowledge to analyze two non‐physiological ligands, HEPES and MES, that are frequent components of crystallization and purifications buffers. Our analysis includes quantum mechanics calculations and Cambridge Structure Database (CSD) queries to define the ideal conformation of these ligands, geometry analysis of PDB deposits regarding several quality factors, and a search for homologous structures to identify other small molecules that could bind in place of the parasitic ligand. Our results highlight the need for careful refinement of macromolecule–ligand complexes and better validation tools that integrate results from all relevant resources.
High Pressure Study of New Type of MAX Phases: Hf2AB2 (A = In, Sn)
Authors: Rahman Md. Atikur , Kholil Ibrahim , Khatun Rukaia , Sarker Sushmita , Hasan Mahbub , Ali Md. Ashraf , Rahaman Md. Zahidur , Hossain Khandaker Monower , Haque Md. Ismail , Hasan Md. Zahid
Published: August 2022

This study carries out density functional theory (DFT)‐based simulation in order to observe the effect of pressure (up to 120 GPa) on the various physical properties of boron (B) containing new MAX compounds Hf2InB2 and Hf2SnB2. Structural parameters in ambient conditions show excellent concordance with prior experimental and theoretical data. A decreasing trend of lattice parameters with pressure is observed. The stability of the phases under pressure is determined by calculating the elastic constant using the Born stability criteria, and is found stable within the studied pressure range. Pressure's effect on the various elastic moduli is considered, and a linear response with pressure is observed. The brittle/ductile behavior under pressure is investigated, and a brittle to ductile phase transition is found. An opposite trend of elastic moduli with pressure is observed for Vickers hardness. The nonlinear variation of Vickers hardness with pressure has been interpreted in terms of Pugh ratio and density of states (DOS). A decreasing trend of the anisotropic indices is observed for Hf2InB2, while an increasing trend is observed for Hf2SnB2. The electronic and optical properties are also significantly influenced by the pressure. The results obtained at zero GPa have been compared with previous results and show significant agreement.
A two‐fluid single‐column model of turbulent shallow convection. Part 1: Turbulence equations in the multifluid framework
Authors: Thuburn John , Efstathiou Georgios A. , McIntyre William A.
Published: August 2022

The multifluid equations are derived from the compressible Euler equations (or any of the usual approximate equation sets used in meteorology) by conditional filtering. They have the potential to provide the basis for an improved representation of cumulus convection and its coupling to the boundary layer and larger scale flow in numerical models. The present article derives the prognostic equations for subfilter‐scale turbulent second moments in the multifluid framework, along with certain systematic simplifications of them, thus providing a multifluid analogue of the well‐known Mellor and Yamada hierarchy of turbulence closures. As well as enabling a more accurate calculation of subfilter‐scale fluxes and the effects of subfilter‐scale variability on cloud fraction, liquid water, and buoyancy, the second moment information can be used to obtain a more accurate parameterization of entrainment and detrainment. A subset of the turbulence equations derived here is employed in the two‐fluid single‐column model described in Part 2 and applied to the simulation of shallow cumulus cases in Part 3.
Actuator fault detection for masonry robot manipulator arm with the interval observer
Authors: Zhao Jinbao , Zhang Ke , Hou Maxiao , Zhang Hao , Bai Yunfei , Huang Yanzheng , Li Jianan
Published: August 2022

The main construction method of building wall is artificial masonry, the main problem is that the process is associated with low construction efficiency and poor safety, workers are prone fall from high altitude. The research of automatic masonry robot has become an urgent need. The masonry mechanical arm system is the main executing part of the masonry robot, special attention should be paid to the robot fault. Therefore, it is necessary to establish a suitable model to detect the actuator faults of the manipulator system. In this paper, a dynamic model of manipulator fault is presented and a fault detection scheme of masonry robot manipulator arm is proposed based on the model. The model is simplified by analyzing the state parameters of each joint during robot masonry and the interval observer with more design freedom was designed based on the established mathematical model of actuator faults. In this paper, a joint method for solving S and L matrices is proposed, which avoids the limitation of the traditional method for solving L matrices by two‐step. In the presence of external interference, / performance are introduced into the generation process of residual interval, and the interval observer has better disturbance robustness and fault sensitivity. Simulation experiments verify that the scheme can effectively detect the actuator fault of the manipulator, and experiments are carried out on a 6‐axis manipulator. The experimental results show that when actuator faults occur at joints 2 and 3, the residual rapidly exceeds the threshold range, which proves the effectiveness of the fault detection scheme designed in this paper.
A function‐based approach to model the measurement error in wearable devices
Authors: Jadhav Sneha , Tekwe Carmen D. , Luan Yuanyuan
Published: August 2022

Physical activity (PA) is an important risk factor for many health outcomes. Wearable‐devices such as accelerometers are increasingly used in biomedical studies to understand the associations between PA and health outcomes. Statistical analyses involving accelerometer data are challenging due to the following three characteristics: (i) high‐dimensionality, (ii) temporal dependence, and (iii) measurement error. To address these challenges we treat accelerometer‐based measures of PA as a single function‐valued covariate prone to measurement error. Specifically, in order to determine the relationship between PA and a health outcome of interest, we propose a regression model with a functional covariate that accounts for measurement error. Using regression calibration, we develop a two‐step estimation method for the model parameters and establish their consistency. A test is also proposed to test the significance of the estimated model parameters. Simulation studies are conducted to compare the proposed methods with existing alternative approaches under varying scenarios. Finally, the developed methods are used to assess the relationship between PA intensity and BMI obtained from the National Health and Nutrition Examination Survey data.