bluuebunny/crossref_metadata_2025 huggingface dataset:
SODplex, a Series of Hierarchical Multiplexed Real-Time PCR Assays for the Detection and Lineage Identification of Phytophthora ramorum, the Causal Agent of Sudden Oak Death and Sudden Larch Death
Authors: Capron Arnaud , Herath Padmini , Alayon D. I. Ojeda , Cervantes Sandra , Day Brittany , Brar Avneet , Bilodeau Guillaume J. , Shamoun Simon F. , Webber Joan , Brasier Clive , Feau Nicolas , Hamelin Richard C.
Published: February 2023

Since its emergence in the 1990s, the invasive pathogen Phytophthora ramorum has spread in Europe and the west coast of North America, causing sudden oak death in the United States and sudden larch death in the United Kingdom, resulting in the mortality or destruction of millions of trees. Due to its invasive nature, its damage potential, its wide host range, and its ability to disseminate via the plant trade, P. ramorum has been placed on quarantine lists worldwide. Rapid and reliable detection of the pathogen and identification of its lineages are crucial to limit spread and inform mitigation and eradication efforts. SODplex, a suite of new multiplex real-time PCR tools, was developed to streamline the detection and identification of P. ramorum. It offers four multiplexed assays covering different use cases. SODplex-base combines primers and probes for the sensitive and accurate detection of Phytophthora spp. and P. ramorum. SODplex-ITS and SODplex-mito offer a single-step identification of P. ramorum and the EU1, NA1, and NA2 lineages present in the United States and Canada. SODplex-lin targets each of the four P. ramorum lineages present in Europe and North America in a single reaction. The assays have high levels of accuracy and are robust to the use of different instruments, different operators, and different temperatures. The redundancy within the assays reduces the likelihood of false negatives and false positives. The SODplex assays presented here improve the toolbox available for the detection of P. ramorum and its lineages.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Oxidative stress induces MUC5AC expression through mitochondrial damage‐dependent STING signaling in human bronchial epithelial cells
Authors: Nishida Yutaka , Yagi Hisako , Ota Masaya , Tanaka Atsushi , Sato Koichiro , Inoue Takaharu , Yamada Satoshi , Arakawa Naoya , Ishige Takashi , Kobayashi Yasuko , Arakawa Hirokazu , Takizawa Takumi
Published: February 2023

Oxidative stress increases the production of the predominant mucin MUC5AC in airway epithelial cells and is implicated in the pathogenesis of bronchial asthma and chronic obstructive pulmonary disease. Oxidative stress impairs mitochondria, releasing mitochondrial DNA into the cytoplasm and inducing inflammation through the intracytoplasmic DNA sensor STING (stimulator of interferon genes). However, the role of innate immunity in mucin production remains unknown. We aimed to elucidate the role of innate immunity in mucin production in airway epithelial cells under oxidative stress. Human airway epithelial cell line (NCI‐H292) and normal human bronchial epithelial cells were used to confirm MUC5AC expression levels by real‐time PCR when stimulated with hydrogen peroxide (H2O2). MUC5AC transcriptional activity was increased and mitochondrial DNA was released into the cytosol by H2O2. Mitochondrial antioxidants were used to confirm the effects of mitochondrial oxidative stress where antioxidants inhibited the increase in MUC5AC transcriptional activity. Cyclic GMP‐AMP synthase (cGAS) or STING knockout (KO) cells were generated to investigate their involvement. H2O2‐induced MUC5AC expression was suppressed in STING KO cells, but not in cGAS KO cells. The epidermal growth factor receptor was comparably expressed in STING KO and wild‐type cells. Thus, mitochondria and STING play important roles in mucin production in response to oxidative stress in airway epithelial cells.
ANP promotes HTR‐8/SVneo cell invasion by upregulating protein kinase N 3 via autophagy inhibition
Authors: Chu Nan , Tang Yao , Wang Cheng‐Jie , Pei Jiang‐Nan , Luo Shou‐Ling , Yu Yi , Liu Zhen‐Zhen , Liu Hai‐Yan , Qiu Xue‐Min , Wang Ling , Li Da‐Jin , Gu Wei‐Rong
Published: February 2023

Preeclampsia is a gestational disease characterized by two major pathological changes‐shallow trophoblast invasion and impaired spiral artery remodeling. Atrial natriuretic peptide (ANP) is a kind of peptide hormone that regulates blood pressure, while the lack of active ANP participates in preeclampsia pathogenesis. However, the underlying mechanism of how ANP modulates trophoblasts function remains unclarified. Here, we performed isobaric tags for relative and absolute quantification (iTRAQ) in ANP‐treated HTR‐8/SVneo cells and identified Protein Kinase 3 (PKN3) as the downstream factor of ANP, which was downregulated in preeclamptic placenta. Chromatin immunoprecipitation analysis and luciferase assays showed that NFYA was one of the transcription factors for the PKN3 promoter, which was also regulated by ANP treatment in HTR‐8/SVneo cells. Transmission electron microscopy and Western Blotting in HTR‐8/SVneo cells indicated that ANP inhibited autophagy via AMPK‐mTORC1 signaling, while excess autophagy was observed in preeclamptic placenta. The increased expression of PKN3 and enhanced cell invasion ability in HTR‐8/SVneo cells induced by ANP could be abolished by autophagy activation or transfection with PKN3 shRNA or NFYA shRNA or NPR‐A shRNA via regulating the invasion‐related genes and the epithelial mesenchymal transition molecules. Our results demonstrated that ANP could enhance trophoblast invasion by upregulating PKN3 via NFYA promotion through autophagy inhibition in an AMPK/mTORC1 signaling‐dependent manner.
Stabilization of nuclear β‐catenin by inhibiting KDM2A mediates cerebral ischemic tolerance
Authors: Zuo Yunyan , Zhan Lixuan , Wen Haixia , Xue Jiahui , Tan Yafu , Sun Weiwen , Xu En
Published: February 2023

Hypoxic postconditioning (HPC) with 8% oxygen increases nuclear accumulation of β‐catenin through activating the classical Wnt pathway, thereby alleviating transient global cerebral ischemia (tGCI)‐induced neuronal damage in the hippocampal CA1 subregion of adult rats. However, little is understood about the regulatory mechanism of nuclear β‐catenin in HPC‐mediated cerebral ischemic tolerance. Although lysine(K)‐specific demethylase 2A (KDM2A) has been known as a crucial regulator of nuclear β‐catenin destabilization, whether it plays an important role through modulating nuclear β‐catenin in cerebral ischemic tolerance induced by HPC remains unknown. In this study, we explored the molecular mechanism of stabilizing nuclear β‐catenin by inhibiting KDM2A‐mediated demethylation in the HPC‐offered neuroprotection against tGCI. In addition, we confirmed that nuclear methylated‐β‐catenin in CA1 decreased and nuclear β‐catenin turnover increased after tGCI, which were reversed by HPC. The administration with methyltransferase inhibitor AdOx abrogated HPC‐induced methylation and stabilization of nuclear β‐catenin in CA1, as well as the neuroprotection against tGCI. Notably, HPC downregulated the expression of KDM2A in CA1 and reduced the interaction between KDM2A and β‐catenin in the nucleus after tGCI. The knockdown of KDM2A with small‐interfering RNA could upregulate nuclear methylated‐β‐catenin and stabilize β‐catenin, thereby increasing survivin in CA1 and improving the cognitive function of rats after tGCI. Opposite results were observed by the administration of KDM2A‐carried adenovirus vector. Furthermore, we demonstrated that KDM2A mediates the demethylation of nuclear β‐catenin through jumonji C (JmjC) domain of KDM2A in HEK‐293T and SH‐SY5Y cells. Our data support that the inhibition of KDM2A‐mediated demethylation of nuclear β‐catenin contributes to HPC‐induced neuroprotection against tGCI.
The Effect of Rural Underserved Opportunities Program Participation on Medical Graduates’ Decision to Work in Rural Areas
Authors: Dahal Arati , Kardonsky Kim , Cunningham Matthew , Evans David V. , Keys Toby
Published: February 2023

Purpose

There is a persistent rural physician shortage in the United States. Policies to scale up the health workforce in response to this shortage must include measures to draw and maintain existing and newly trained health care workers to rural regions. Prior studies have found that experience in community medicine in rural practice settings increases the likelihood of medical graduates practicing in those regions but have not accounted for selection bias. This study examined the impact of a community-based clinical immersion program on medical graduates’ decision to work in rural regions, adjusting for covariates to control for selection bias.

Method

Data on sociodemographic characteristics and career interests and preferences for all 1,172 University of Washington School of Medicine graduates between 2009 and 2014 were collected. A logistic model (model 1) was used to evaluate the impact of Rural Underserved Opportunities Program (RUOP) participation on the probability of physicians working in a rural region. Another model (model 2) included the propensity score as a covariate in the regression to control for possible confounding based on differences among those who did and did not participate in the RUOP.

Results

Of the 994 students included in the analysis, 570 (57.3%) participated in RUOP training, and 111 (11.2%) were currently working in rural communities after their training. Regression analysis results showed that the odds of working in a rural region were 1.83 times higher for graduates who participated in RUOP in model 1 (P = .03) and 1.77 times higher in model 2 (P = .04).

Conclusions

The findings of this study emphasize that educational programs and policies are crucial public health interventions that can promote health equity through proper distribution of health care workers across rural regions of the United States.
Characteristics of forearm refracture in adolescents
Authors: Kapadia Ami B. , Wilson Philip L. , Gill Corey S. , Wyatt Charles W. , Montgomery Gerad K. , Huang Sharon G. , Ellis Henry B.
Published: February 2023

The purpose of this study was to evaluate characteristics of reinjury following forearm fractures in adolescents. An Institutional Review Board-approved retrospective cohort study of forearm fractures (ages 10–18 years) treated by a single academic pediatric orthopaedic group from June 2009 to May 2020 was conducted. All both bone forearm (BBFA) and radius or ulna primary and secondary injuries were included. We excluded open, surgically treated, physeal, epiphyseal, and radial head/neck fractures. Demographics, injury characteristics, and radiographic data were recorded. We evaluated associations of ipsilateral same-site refracture (RE-FRACTURE) versus ipsilateral or contralateral different-site forearm fractures occurring as secondary later injuries (OTHER). Thirty-three of 719 patients sustained a secondary forearm fracture (4.6%; mean age, 11.5 years; M:F, 5.6:1). RE-FRACTURES, compared with OTHER forearm locations, were associated with a sports mechanism at time of original injury (P = 0.024) and mid-shaft position of fracture on the radius (77.6 vs. 29.8 mm from distal physis; P < 0.001) and ulna (72.0 vs. 27.2 mm from distal physis; P = 0.003). RE-FRACTURES also demonstrated increased radius to ulna distance between BBFA primary injury sites on anteroposterior (19.6 vs. 10.6 mm; P = 0.009) and lateral radiographs (19.6 vs. 10.5 mm; P = 0.020) compared with OTHER forearm locations. Residual angulation and fracture-line visibility were not significantly associated with secondary fracture. Ipsilateral same-site refractures tend to occur in adolescents within 1 year following treatment for widely spaced (>15 mm) and mid-shaft forearm fractures incurred during athletic activity. Further research may be warranted to evaluate biologic, bone health, or personality traits that may lead to secondary fractures of the pediatric forearm.
Current “state of the art” on dendritic cell-based cancer vaccines in melanoma
Authors: Schwarze Julia Katharina , Geeraerts Xenia , Tuyaerts Sandra , Neyns Bart
Published: February 2023

Purpose of review

Dendritic cells (DCs) are the gatekeepers of our immune system and indispensable in the antitumor immune response. In recent years, their classification has been revised considerably using single-cell sequencing approaches. In this review, we focus on their unique role in cancer and how specific DC subsets can be manipulated to induce an effective and durable antitumor response.

Recent findings:

Historically, due to the ease of their isolation in sufficient cell numbers from peripheral blood, the utility of monocyte-derived DCs as therapeutic cancer vaccines was explored in the clinic. However, it became clear that naturally circulating myeloid DCs (myDC), exerting their physiological role, are a functionally more powerful cellular source of antigen presenting cells. With the advent of immunomagnetic bead technology to isolate naturally circulating DC subsets, the therapeutic value of these myDC subsets is currently being explored. Since DCs are also needed in the tumor microenvironment in order to “relicense” the activity of antitumor T cells, also intratumoral administration routes for DC vaccines are explored. In addition, to circumvent the use of expensive cellular vaccines, approaches to attract DCs to the tumor microenvironment are considered of interest in order to repair a defective cancer-immunity cycle.

In recent years, the type of DCs used for vaccination and their administration route evolved considerably. Intratumoral vaccination strategies require combination with additional stimuli to ensure proper functioning of DCs in the tumor microenvironment. Moreover, intratumoral administration limits the applicability to patients with accessible lesions.
Estimation of the population, death, and quality of life in Shaanxi Province, western China: a cross-sectional study
Authors: Miao Xinlei , Chen Jun , Wu Qiong , Meng Wen , Ren Lin , Wu Zhiyuan , Guo Xiuhua , Zhang Xiang , Meng Qun
Published: February 2023

Background:

Measuring the health of the population is of great significance to the development of a region. We aimed to estimate the population, probability of death, and quality of life in western China.

Methods:

We calculated the age-specific mortality rate and prevalence rate of diseases and injuries using the Full Population Database and the Home Page of Inpatient Medical Record. We used multiple interpolation methods to insert missing information from the death data and the model of Kannisto to adjust the mortality rate for elderly individuals. The age-specific prevalence rate of diseases and injuries was adjusted according to the standard ratio of age and methods of equal proportional allocation. Life expectancy was calculated by a life table, and the quality of life was estimated using the Sullivan method.

Results:

The total population continued to increase in 2015 to 2019 in the Shaanxi Province, China. The mortality rate of children under 5 has improved, and the mortality rate of people over 65 is decreasing year by year. Life expectancy increased from 74.66 years in 2015 to 77.19 years in 2019. Even with the total risk of disease and injury, the health-adjusted life expectancy increased 1.90 years within 5 years, and the number of unhealthy years significantly improved. Health-adjusted life expectancy increased 1.75 years when only considered the ten major disease systems (tumours; endocrinology, nutrition and metabolism; mental and behavioral disorders; nervous system; sensory diseases; circulatory system; respiratory system; digestive system; genitourinary system; musculoskeletal system and connective tissue), and the number of unhealthy years increased slightly.

Conclusions:

In the past five years, Shaanxi Province has made progress in improving life expectancy and controlling the development of chronic diseases. It is necessary to take specific preventive measures and improve the quality of basic public health services.
Cardiopulmonary Exercise Testing in Heart Failure With Preserved Ejection Fraction: Technique Principles, Current Evidence, and Future Perspectives
Authors: Boulmpou Aristi , Boutou Afroditi K. , Pella Eva , Sarafidis Pantelis , Papadopoulos Christodoulos E. , Vassilikos Vassilios
Published: February 2023

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial clinical syndrome involving a rather complex pathophysiologic substrate and quite a challenging diagnosis. Exercise intolerance is a major feature of HFpEF, and in many cases, diagnosis is suspected in subjects presenting with exertional dyspnea. Cardiopulmonary exercise testing (CPET) is a noninvasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, hematopoietic, neuropsychological, and metabolic functions during maximal or submaximal exercise. The assessment is based on the principle that system failure typically occurs when the system is under stress, and thus, CPET is currently considered to be the gold standard for identifying exercise intolerance, allowing the differential diagnosis of underlying causes. CPET is used in observational studies and clinical trials in HFpEF; however, in most cases, only a few from a wide variety of CPET parameters are examined, while the technique is largely underused in everyday cardiology practice. This article discusses the basic principles and methodology of CPET and studies that utilized CPET in patients with HFpEF, in an effort to increase awareness of CPET capabilities among practicing cardiologists.
Trends in stroke, cardiovascular disease, and medical expenditure under a community-based long-term stroke prevention program
Authors: Yamagishi Kazumasa , Sankai Tomoko , Muraki Isao , Umesawa Mitsumasa , Cui Renzhe , Imano Hironori , Kihara Tomomi , Noda Hiroyuki , Ikeda Ai , Ohira Tetsuya , Tanigawa Takeshi , Kitamura Akihiko , Sato Shinichi , Kiyama Masahiko , Iso Hiroyasu
Published: February 2023

Background:

Evidence on the effects of preventive measures for noncommunicable disease is urgently needed for low-income and middle-income countries suffering from stroke epidemics along with population aging.

Objectives:

We sought to examine the impact of a community-based stroke prevention program on incidences of stroke and ischemic heart disease, mortality from cardiovascular disease, and medical expenditure.

Methods:

Trends in the incidences of stroke and ischemic heart disease were documented in a Japanese rural community, Kyowa, from 1981 through 2015. Trends in mortality from cardiovascular disease and in medical expenditures were compared between Kyowa and its surrounding municipalities from 1981 through 2004.

Results:

In Kyowa, the age and-sex-adjusted incidences of stroke and of ischemic heart disease decreased by half (from 4.1 to 1.9 and from 1.5 to 0.7 per year/1000 persons, respectively) over the past 35 years. A similar decreasing trend was observed for the age and-sex-adjusted mortality from cardiovascular disease, and this decreasing trend occurred earlier than that in the surrounding municipalities. The medical expenditures for cardiovascular disease became lower in Kyowa than in the surrounding municipalities over time.

Conclusion:

Our study's findings suggest that a community-based stroke prevention program augmented the decline in the incidences of stroke and ischemic heart disease, mortality from cardiovascular disease, and attenuated the increase in medical expenditures for cardiovascular disease.
How acute renal failure led to the diagnosis of aortic coarctation
Authors: Kantauskaite Marta , Fürst Günter , Minko Peter , Antoch Gerald , Rump Lars Christian , Potthoff Sebastian A.
Published: February 2023

The present case report focuses on a rare presentation of aortic coarctation. A 38-year-old man with well-controlled arterial hypertension, minimal change glomerulonephritis and colitis ulcerosa was suffering from recurrent acute renal failure episodes during viral gastroenteritis. No other symptoms at rest or during physical activity were present. The workup included renal duplex sonography, which unmasked tardus parvus profile in both kidneys without any acceleration of blood flow in the renal arteries. Further examination included CT angiography, which confirmed the diagnosis of aortic coarctation. The observed narrowing of the aorta measured 4 mm and was treated with percutaneous transluminal angioplasty and stent implantation (final diameter 12 mm). After the procedure, the patient had normal blood pressure values without the need of any medication; duplex sonography showed improved renal perfusion. The present case confirms the importance of evaluation for secondary hypertension and thorough workup of acute renal failure in young patients.
The relationship between arginine vasopressin gene polymorphisms and plasma copeptin and hypertensive disorders of pregnancy: a nested case-control study
Authors: Sun Yexiu , Guo Ying , Xu He , Zhao Ji , Wu Di , Hu Jianwei , Wang Dandan , Wu Lei , Peng Hao , Li Hongmei
Published: February 2023

Objectives:

This study aims to explore the relationship between polymorphism of the arginine vasopressin (AVP) gene and plasma copeptin concentration with the occurrence of hypertension in pregnancy.

Methods:

We conducted a matched nested case–control study in Chinese women. The genotypes of rs3729965, rs3761249, rs1410713, rs2740204, and rs2282018 loci of AVP gene and plasma copeptin at 16–20 gestational weeks were detected in 288 patients with gestational hypertension (GH), 82 with preeclampsia (PE), and 14 with chronic hypertension with superimposed preeclampsia (CH-PE) and their healthy matched controls.

Results:

For every natural logarithm unit increment in copeptin, the risks of GH and PE/CH-PE increased by 5.556 (adjusted odds ratio [aOR]: 6.556, 95% confidence interval [CI]: 2.734–15.717) and 3.312 times (aOR: 4.312, 95% CI: 1.168–15.914). Under the dominant model, the genotype CC + CT of rs2282018 and GG + GT of rs3761249 had higher risks of GH than genotype TT, with aORs of 1.757 (95% CI: 1.077–2.867) and 1.814 (95% CI: 1.111–2.963). Allele A of rs3729965 loci had a lower risk of PE/CH-PE than allele G (aOR: 0.441, 95% CI: 0.199–0.978). However, the frequencies of rs1410713 and rs2740204 genotypes were not significantly different between cases and controls. The model of copeptin combined with the AVP gene and traditional factors (TFs) had a higher ability than the TFs model in predicting GH and PE/CH-PE.

Conclusion:

Our study confirms that higher plasma copeptin and AVP gene variants are associated with the occurrence of GH and PE/CH-PE. The detection of copeptin and AVP gene in the early second trimester improves the predictive ability of TFs for GH and PE/CH-PE.
Virtual Physician Assistant Program Interviews: Faculty and Applicant Perspectives
Authors: Loscalzo Carina , Kuriakose Shinu , Timko-Swaim Lynn , L’Eplattenier Mark
Published: February 2023

Introduction

Many physician assistant (PA) programs converted from traditional in-person admission interviews to virtual interviews during the COVID-19 pandemic. The purpose of this study was to investigate the perceptions of both PA faculty and applicants to PA programs about the virtual interview process. General perceptions, advantages, and disadvantages were explored.

Methods

A mixed-method approach was implemented to collect data using 2 survey instruments: one for PA program applicants and another for PA program faculty. The surveys were created using a combination of previously used and new questions and distributed through email and social media. Descriptive statistics were used to analyze the independent and dependent variables. Chi-square, one-way ANOVA, and Spearman’s rho correlation were conducted to analyze potential relationships between variables. Qualitative data were analyzed using an iterative process and inductive reasoning to identify recurring themes and code responses into common topical categories.

Results

Completed surveys were received from 178 applicants and 325 faculty members. If given the choice, most applicants favored virtual interviews (62.4%), while the majority of faculty preferred in-person interviews (64.0%). The majority of applicants (84.6%) and faculty (64.9%) were comfortable making a decision about the program or applicant, respectively, after the virtual interview process. The top 3 advantages of virtual interviewing for both faculty and applicants included convenience, decreased travel time, and cost savings.

Discussion

Both faculty and applicants perceived the virtual interview process positively, and thus, this modality may have enough advantages to support its use in the future.
Impact of Perceived Cooking Skills on Eating Habits Among Young Adults
Authors: Puri Achira , Jaiswal Nidhi
Published: February 2023

This review characterizes the impact that perceived cooking skills and psychological characteristics can have on young adults' eating habits, with particular emphasis on young Asian Indian adults. It concludes that cooking skills do have a positive impact on their eating habits. However, psychological factors, such as cooking confidence, willingness to cook, time available, health consciousness, personal interest, and other factors, are also associated with eating habits.
Building Global Consensus on Nutrition Metrics to Support Food System Transformation: A Dairy Case Study
Authors: Miller Gregory D. , McMahan Joe , Ragalie-Carr Jean , Maisano Megan , Brown Katie
Published: February 2023

A new assessment, conducted by nutrition and environmental scientists within the dairy sector, underscores the need to improve the characterization and reporting of nutrition and health outcomes in the context of food system transformation. To date, global stakeholders have more narrowly prioritized the environmental aspects of sustainable food production and diets. The urgent next step is to draw from established nutrition/health-focused frameworks to align global stakeholders around a consistent set of metrics and indicators that are measurable and evidence-based and accurately reflect benefits and harms to public nutrition and health.
Design and evaluation of a hip prosthesis simulator: A technical note
Authors: Fanous Amir , Botros Michael , Gholizadeh Hossein , Baddour Natalie , Lemaire Edward D.
Published: February 2023

People with a limb loss at the level of the hip or pelvis have the most difficulty returning to walking compared with those with a lower amputation. This is because their prosthesis must replace the hip, knee, and ankle joints. An adjustable hip-disarticulation/hemipelvectomy prosthesis simulator that allows able-bodied individuals to wear and assess a prosthesis can help researchers and manufacturers when designing new prosthetic components (ie, hip joints). SolidWorks computer-aided design software was used to design and simulate an adapter that can connect prosthetic components to an off-the-shelf hip abduction orthosis. The adapter was made of 1020 stainless steel and aluminium 6061-T3 with a yield strength of 276 MPa. To confirm that this adapter is strong and safe for ambulation, mechanical testing was performed using an INSTRON machine. The maximum loads generated in any activity were chosen according to the International Organization for Standardization 15032:2000 standard for hip disarticulation external prostheses. The designed adapter allowed frontal, lateral, or distal mounting of different prosthetic hip joints. Mechanical testing confirmed that the new adapter can withstand forces and moments experienced during ambulation. The hip disarticulation/hemipelvectomy prosthesis simulator is easy to use and adjustable based on each person’s height and pelvic width. Furthermore, this simulator would assist rehabilitation practitioners in experiencing the use of hip-level prostheses and give them a better understanding of people using such technologies. The next step in this project is to evaluate able-bodied participant gait while using this hip simulator prosthesis with different hip joints.
68Ga-FAPI PET/CT Imaging of Intracranial Syphilitic Gumma
Authors: Gong Weidong , Qiu Shuang , Zheng Shiyu , Liu Wei , Zhang Chunyin
Published: February 2023

Intracranial syphilitic gumma is a rare neurological disease. We present 68Ga-DOTA-FAPI-04 and 18F-FDG PET/CT findings of intracranial syphilitic gumma in a 46-year-old man with HIV. In this case, 68Ga-DOTA-FAPI-04 PET/CT outperforms 18F-FDG in helping to visualizing syphilitic gumma. Syphilitic gumma can also cause increase FAPI activity. Our findings suggest the potential value of 68Ga-DOTA-FAPI-04 in the diagnosis of syphilis.
68Ga–DOTA–Exendin-4 PET/CT Demonstrated a Higher Detection Efficacy for Double-Primary Insulinomas Than MRI
Authors: Qiu Lin , Lan Lianjun , Cai Liang , Chen Lin , Chen Yue
Published: February 2023

We presented a 20-year-old woman with gradually increasing lethargy and multiple episodes of dizziness for 5 months. The laboratory examination revealed decreasing level of blood glucose and elevated levels of fasting plasma insulin and C-peptide. The MRI identified a focal nodule in the tail of the pancreas. 68Ga–DOTA–exendin-4 PET/CT revealed 2 intense focal tracer uptakes in the tail of the pancreas, one of which corresponded to the lesion revealed on MRI. The immunohistochemical results of resected samples confirmed the diagnosis of double-primary insulinomas. 68Ga–DOTA–exendin-4 PET/CT demonstrated excellent localization and characterization for double-primary insulinomas in the tail of the pancreas.
Solitary Accessory Spleen-Like Metastasis Coexisted With Splenic Infarction Reveled on 18F-FDG PET/CT in a Hepatocellular Carcinoma Patient
Authors: Shao Fuqiang , Xie Peng
Published: February 2023

Solitary parasplenic metastatic carcinoma may be misinterpreted as accessory spleen on CT images. In addition, elevated FDG uptake in the spleen may also mimic metastasis in patient with a history of carcinoma. Here we present a case of parasplenic metastasis coexisted with splenic infarction reveled on 18F-FDG PET/CT in a 51-year-old man with history of hepatocellular carcinoma.
Renal Ischemia–reperfusion Injury Attenuated by Exosomes Extracted From Splenic Ischemic Preconditioning Models
Authors: Liu Hongtao , Shen Ye
Published: February 2023

Background.

To investigate the protective effects of exosomes extracted from splenic ischemic preconditioning (sIPC) models on renal ischemia–reperfusion injury (IRI).

Methods.

sIPC was conducted on mice before renal IRI, and exosomes derived from sIPC mice were infused into a mouse model of renal IRI. The kidney tissue and serum were collected 24 h later. The morphological changes, inflammation and apoptosis in IR kidneys were determined by hematoxylin–eosin (HE), terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), and Ki-67 immunohistochemical staining. In addition, the proinflammatory cytokines in serum and cell supernatant were measured with enzyme-linked immunosorbent assays (ELISAs). Then, we administered exosomes to mouse renal epithelial cells. TUNEL assays and flow cytometry were used to evaluate cell apoptosis. Bax and Bcl-2 levels were measured via Western blotting.

Results.

HE staining showed that the renal IRI was attenuated after sIPC. TUNEL results showed that renal tissue apoptosis was greatly reduced after sIPC or injection of exosomes. ELISAs showed that the serum creatinine (sCr), tumor necrosis factor alpha, and interleukin-1 β levels induced by IRI decreased with sIPC. In vitro, exosomes extracted from the hypoxia/reoxygenation (H/R) splenic fibroblast model had the same protective effect. TUNEL and flow cytometry results showed that the exosomes reduced apoptosis. ELISAs showed that tumor necrosis factor alpha and interleukin-1 β were significantly increased in the H/R group but decreased due to the exosomes treated with starvation. WB results showed that Bax expression was increased and Bcl-2 expression was decreased in the H/R group. However, exosomes decreased the Bax level and increased the Bcl-2 level.

Conclusions.

Exosomes extracted from sIPC models exerted a protective effect to attenuate renal IRI.
Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion
Authors: de Jong Iris E.M. , Bodewes Silke B. , van Leeuwen Otto B. , Oosterhuis Dorenda , Lantinga Veerle A. , Thorne Adam M. , Lascaris Bianca , van den Heuvel Marius C. , Wells Rebecca G. , Olinga Peter , de Meijer Vincent E. , Porte Robert J.
Published: February 2023

Background.

End-ischemic ex situ normothermic machine perfusion (NMP) enables assessment of donor livers prior to transplantation. The objective of this study was to provide support for bile composition as a marker of biliary viability and to investigate whether bile ducts of high-risk human donor livers already undergo repair during NMP.

Methods.

Forty-two livers that were initially declined for transplantation were included in our NMP clinical trial. After NMP, livers were either secondary declined (n = 17) or accepted for transplantation (n = 25) based on the chemical composition of bile and perfusate samples. Bile duct biopsies were taken before and after NMP and assessed using an established histological injury severity scoring system and a comprehensive immunohistochemical assessment focusing on peribiliary glands (PBGs), vascular damage, and regeneration.

Results.

Bile ducts of livers that were transplanted after viability testing during NMP showed better preservation of PBGs, (micro)vasculature, and increased cholangiocyte proliferation, compared with declined livers. Biliary bicarbonate, glucose, and pH were confirmed as accurate biomarkers of bile duct vitality. In addition, we found evidence of PBG-based progenitor cell differentiation toward mature cholangiocytes during NMP.

Conclusions.

Favorable bile chemistry during NMP correlates well with better-preserved biliary microvasculature and PBGs, with a preserved capacity for biliary regeneration. During NMP, biliary tree progenitor cells start to differentiate toward mature cholangiocytes, facilitating restoration of the ischemically damaged surface epithelium.
Obinutuzumab Effectively Depletes Key B-cell Subsets in Blood and Tissue in End-stage Renal Disease Patients
Authors: Looney Cary M. , Schroeder Aaron , Tavares Erica , Garg Jay , Schindler Thomas , Vincenti Flavio , Redfield Robert R. , Jordan Stanley C. , Busque Stephan , Woodle E. Steve , Khan Jared , Eastham Jeffrey , Micallef Sandrine , Austin Cary D. , Morimoto Alyssa
Published: February 2023

Background.

The THEORY study evaluated the effects of single and multiple doses of obinutuzumab, a type 2 anti-CD20 antibody that induces antibody-dependent cell-mediated cytotoxicity and direct cell death, in combination with standard of care in patients with end-stage renal disease.

Methods.

We measured B-cell subsets and protein biomarkers of B-cell activity in peripheral blood before and after obinutuzumab administration in THEORY patients, and B-cell subsets in lymph nodes in THEORY patients and an untreated comparator cohort.

Results.

Obinutuzumab treatment resulted in a rapid loss of B-cell subsets (including naive B, memory B, double-negative, immunoglobulin D+ transitional cells, and plasmablasts/plasma cells) in peripheral blood and tissue. This loss of B cells was associated with increased B cell–activating factor and decreased CXCL13 levels in circulation.

Conclusions.

Our data further characterize the mechanistic profile of obinutuzumab and suggest that it may elicit greater efficacy in indications such as lupus where B-cell targeting therapeutics are limited by the resistance of pathogenic tissue B cells to depletion.
Numerical instability of Hill-type muscle models
Authors: Yeo Sang-Hoon , Verheul Jasper , Herzog Walter , Sueda Shinjiro
Published: February 2023

Hill-type muscle models are highly preferred as phenomenological models for musculoskeletal simulation studies despite their introduction almost a century ago. The use of simple Hill-type models in simulations, instead of more recent cross-bridge models, is well justified since computationally ‘light-weight’—although less accurate—Hill-type models have great value for large-scale simulations. However, this article aims to invite discussion on numerical instability issues of Hill-type muscle models in simulation studies, which can lead to computational failures and, therefore, cannot be simply dismissed as an inevitable but acceptable consequence of simplification. We will first revisit the basic premises and assumptions on the force–length and force–velocity relationships that Hill-type models are based upon, and their often overlooked but major theoretical limitations. We will then use several simple conceptual simulation studies to discuss how these numerical instability issues can manifest as practical computational problems. Lastly, we will review how such numerical instability issues are dealt with, mostly in an ad hoc fashion, in two main areas of application: musculoskeletal biomechanics and computer animation.
Echinoid skeleton: an insight on the species-specific pattern of the
Paracentrotus lividus
plate and its microstructural variability
Authors: Perricone Valentina , Cesarano Pasquale , Mancosu Andrea , Asnicar Davide , Bravi Sergio , Marmo Francesco
Published: February 2023

The skeletal plates of echinoids consist of a peculiar lightweight structure, called stereom, which is organized in a porous three-dimensional lattice-like meshwork. The stereom is characterized by an extremely complex and diverse microarchitecture, largely varying not only from species to species but also among different test plates. It consists of different basic types combined in extremely different ways according to specific functional needs, creating species-specific structural patterns. These patterns can lead to specific mechanical behaviours, which can inspire biomimetic technology and design development. In this framework, the present study aimed to characterize the species-specific pattern of the
Paracentrotus lividus
interambulacral plate and the main microstructural features regarding its geometrical variability and mechanical responses. The results achieved quantitatively highlighted the differences between the analysed stereom types providing new insights regarding their topological configuration and isotropic and anisotropic behaviour. Interestingly, data also revealed that the galleried stereom present at the tubercle is significantly different from the one located at the suture. These analyses and findings are encouraging and provide a starting point for future research to unravel the wide range of mechanical strategies evolved in the echinoid skeletal structure.
Raising the value of research studies in psychological science by increasing the credibility of research reports: the transparent Psi project
Authors: Kekecs Zoltan , Palfi Bence , Szaszi Barnabas , Szecsi Peter , Zrubka Mark , Kovacs Marton , Bakos Bence E. , Cousineau Denis , Tressoldi Patrizio , Schmidt Kathleen , Grassi Massimo , Evans Thomas Rhys , Yamada Yuki , Miller Jeremy K. , Liu Huanxu , Yonemitsu Fumiya , Dubrov Dmitrii , Röer Jan Philipp , Becker Marvin , Schnepper Roxane , Ariga Atsunori , Arriaga Patrícia , Oliveira Raquel , Põldver Nele , Kreegipuu Kairi , Hall Braeden , Wiechert Sera , Verschuere Bruno , Girán Kyra , Aczel Balazs
Published: February 2023

The low reproducibility rate in social sciences has produced hesitation among researchers in accepting published findings at their face value. Despite the advent of initiatives to increase transparency in research reporting, the field is still lacking tools to verify the credibility of research reports. In the present paper, we describe methodologies that let researchers craft highly credible research and allow their peers to verify this credibility. We demonstrate the application of these methods in a multi-laboratory replication of Bem's Experiment 1 (Bem 2011J. Pers. Soc. Psychol.100, 407–425. (doi:10.1037/a0021524)) on extrasensory perception (ESP), which was co-designed by a consensus panel including both proponents and opponents of Bem's original hypothesis. In the study we applied direct data deposition in combination with born-open data and real-time research reports to extend transparency to protocol delivery and data collection. We also used piloting, checklists, laboratory logs and video-documented trial sessions to ascertain as-intended protocol delivery, and external research auditors to monitor research integrity. We found 49.89% successful guesses, while Bem reported 53.07% success rate, with the chance level being 50%. Thus, Bem's findings were not replicated in our study. In the paper, we discuss the implementation, feasibility and perceived usefulness of the credibility-enhancing methodologies used throughout the project.
The process of replication target selection in psychology: what to consider?
Authors: Pittelkow Merle-Marie , Field Sarahanne M. , Isager Peder M. , van’t Veer Anna E. , Anderson Thomas , Cole Scott N. , Dominik Tomáš , Giner-Sorolla Roger , Gok Sebahat , Heyman Tom , Jekel Marc , Luke Timothy J. , Mitchell David B. , Peels Rik , Pendrous Rosina , Sarrazin Samuel , Schauer Jacob M. , Specker Eva , Tran Ulrich S. , Vranka Marek A. , Wicherts Jelte M. , Yoshimura Naoto , Zwaan Rolf A. , van Ravenzwaaij Don
Published: February 2023

Increased execution of replication studies contributes to the effort to restore credibility of empirical research. However, a second generation of problems arises: the number of potential replication targets is at a serious mismatch with available resources. Given limited resources, replication target selection should be well-justified, systematic and transparently communicated. At present the discussion on what to consider when selecting a replication target is limited to theoretical discussion, self-reported justifications and a few formalized suggestions. In this Registered Report, we proposed a study involving the scientific community to create a list of considerations for consultation when selecting a replication target in psychology. We employed a modified Delphi approach. First, we constructed a preliminary list of considerations. Second, we surveyed psychologists who previously selected a replication target with regards to their considerations. Third, we incorporated the results into the preliminary list of considerations and sent the updated list to a group of individuals knowledgeable about concerns regarding replication target selection. Over the course of several rounds, we established consensus regarding what to consider when selecting a replication target. The resulting checklist can be used for transparently communicating the rationale for selecting studies for replication.
Difficulty-skill balance does not affect engagement and enjoyment: a pre-registered study using artificial intelligence-controlled difficulty
Authors: Cutting Joe , Deterding Sebastian , Demediuk Simon , Sephton Nick
Published: February 2023

How does the difficulty of a task affect people's enjoyment and engagement? Intrinsic motivation and flow theories posit a ‘goldilocks’ optimum where task difficulty matches performer skill, yet current work is confounded by questionable measurement practices and lacks scalable methods to manipulate objective difficulty-skill ratios. We developed a two-player tactical game test suite with an artificial intelligence (AI)-controlled opponent that uses a variant of the Monte Carlo Tree Search algorithm to precisely manipulate difficulty-skill ratios. A pre-registered study (n= 311) showed that our AI produced targeted difficulty-skill ratios without participants noticing the manipulation, yet different ratios had no significant impact on enjoyment or engagement. This indicates that difficulty-skill balance does not always affect engagement and enjoyment, but that games with AI-controlled difficulty provide a useful paradigm for rigorous future work on this issue.
Unsupervised machine learning discovers classes in aluminium alloys
Authors: Bhat Ninad , Barnard Amanda S. , Birbilis Nick
Published: February 2023

Aluminium (Al) alloys are critical to many applications. Although Al alloys have been commercially widespread for over a century, their development has predominantly taken a trial-and-error approach. Furthermore, many discrete studies regarding Al alloys, often application specific, have precluded a broader consolidation of Al alloy classification. Iterative label spreading (ILS), an unsupervised machine learning approach, was used to identify the different classes of Al alloys, drawing from a specifically curated dataset of 1154 Al alloys (including alloy composition and processing conditions). Using ILS, eight classes of Al alloys were identified based on a comprehensive feature set under two descriptors. Further, a decision tree classifier was used to validate the separation of classes.
Multi-fidelity modelling of shark skin denticle flows: insights into drag generation mechanisms
Authors: Lloyd C. J. , Mittal K. , Dutta S. , Dorrell R. M. , Peakall J. , Keevil G. M. , Burns A. D.
Published: February 2023

We investigate the flow over smooth (non-ribletted) shark skin denticles in an open-channel flow using direct numerical simulation (DNS) and two Reynolds averaged Navier–Stokes (RANS) closures. Large peaks in pressure and viscous drag are observed at the denticle crown edges, where they are exposed to high-speed fluid which penetrates between individual denticles, increasing shear and turbulence. Strong lift forces lead to a positive spanwise torque acting on individual denticles, potentially encouraging bristling if the denticles were not fixed. However, DNS predicts that denticles ultimately increase drag by 58% compared to a flat plate. Good predictions of drag distributions are obtained by RANS models, although an underestimation of turbulent kinetic energy production leads to an underprediction of drag. Nevertheless, RANS methods correctly predict trends in the drag data and the regions contributing most to viscous and pressure drag. Subsequently, RANS models are used to investigate the dependence of drag on the flow blockage ratio (boundary layer to roughness height ratio), finding that the drag increase due to denticles is halved when the blockage ratio
δ
/
h
is increased from 14 to 45. Our results provide an integrated understanding of the drag over non-ribletted denticles, enabling existing diverse drag data to be explained.
Recognizability bias in citizen science photographs
Authors: Koch Wouter , Hogeweg Laurens , Nilsen Erlend B. , O’Hara Robert B. , Finstad Anders G.
Published: February 2023

Citizen science and automated collection methods increasingly depend on image recognition to provide the amounts of observational data research and management needs. Recognition models, meanwhile, also require large amounts of data from these sources, creating a feedback loop between the methods and tools. Species that are harder to recognize, both for humans and machine learning algorithms, are likely to be under-reported, and thus be less prevalent in the training data. As a result, the feedback loop may hamper training mostly for species that already pose the greatest challenge. In this study, we trained recognition models for various taxa, and found evidence for a
‘recognizability bias’
, where species that are more readily identified by humans and recognition models alike are more prevalent in the available image data. This pattern is present across multiple taxa, and does not appear to relate to differences in picture quality, biological traits or data collection metrics other than recognizability. This has implications for the expected performance of future models trained with more data, including such challenging species.