bluuebunny/crossref_metadata_2025 huggingface dataset:
“You are not a man”: a multi‐method study of trans stigma and risk of HIV and sexually transmitted infections among trans men in Uganda
Authors: Mujugira Andrew , Kasiita Vicent , Bagaya Monica , Nakyanzi Agnes , Bambia Felix , Nampewo Oliva , Kamusiime Brenda , Mugisha Jackson , Nalumansi Alisaati , Twesigye Collin C. , Muwonge Timothy R. , Baeten Jared M. , Wyatt Monique A. , Tsai Alexander C. , Ware Norma C. , Haberer Jessica E.
Published: December 2021

Introduction

Transgender (trans) men in sub‐Saharan Africa are a hidden and vulnerable population who may engage in sex work due to socio‐economic exclusion and lack of alternative employment opportunities. Little is known about HIV and sexually transmitted infection (STI) risk among trans men in this setting. We conducted a multi‐method study to characterize HIV/STI risk among trans men in Uganda.

Methods

Between January and October 2020, we enrolled 50 trans men into a cross‐sectional study through snowball sampling. Data were collected on socio‐demographic characteristics, sexual practices and depression. We conducted 20 qualitative interviews to explore: (1) descriptions of sexual practices that could increase HIV/STI exposure; (2) experiences of accessing public healthcare facilities; (3) perceptions of HIV or STI testing; (4) HIV and STI service delivery; and (5) drug and alcohol use. We used an inductive content analytic approach centring on descriptive category development to analyse the data.

Results

The median age was 25 years (interquartile range 23–28). The prevalence of HIV, syphilis and hepatitis B was 4%, 6% and 8%, respectively. We observed multiple levels of intersecting individual, interpersonal and structural stigmas. (1) Trans men reported transphobic rape motivated by interpersonal stigma that was psychologically traumatizing to the survivor. The resultant stigma and shame hindered healthcare access. (2) Structural stigma and economic vulnerability led to sex work, which increased the risk of HIV and other STIs. Sex work stigma further compounded vulnerability. (3) Individualized stigma led to fear of disclosure of gender identity and HIV status. Concealment was used as a form of stigma management. (4) Multiple levels of stigma hampered access to healthcare services. Preference for trans‐friendly care was motivated by stigma avoidance in public facilities. Overall, the lived experiences of trans men highlight the intertwined relationship between stigma and sexual health.

Conclusions

In this sample from Uganda, trans men experienced stigma at multiple levels, highlighting the need for gender‐sensitive healthcare delivery. Stigma reduction interventions, including provider training, non‐discrimination policies, support groups and stigma counselling, could strengthen uptake and utilization of prevention services by this marginalized population.
The macroeconomic impact of COVID‐19 in Mozambique: A social accounting matrix approach
Authors: Betho Rosario , Chelengo Marcia , Jones Sam , Keller Michael , Mussagy Ibraimo Hassane , van Seventer Dirk , Tarp Finn
Published: December 2021

This study assesses the economic costs of COVID‐19 and the state of emergency implemented by the Government of Mozambique. We use a social accounting matrix multiplier analysis to estimate the effects of the pandemic on the economy. Our simulations suggest that the Mozambican economy lost 3.6 percentage points of GDP growth in 2020 and that employment was 1.9 percentage points down. These losses were primarily driven by export shocks, the most heavily affected sectors being trade and accommodation and mining. Mozambique faces a critical challenge of how to promote economic diversification and reduce vulnerability to foreign shocks.
Extended recovery of cardiac function after severe infantile cardiomyopathy presentation of Barth syndrome
Authors: Yester Jessie , Feingold Brian
Published: December 2021

Cardiomyopathy is the most common presenting feature of Barth syndrome, often presenting in infancy with severe heart failure and cardiac dysfunction. Historically, affected infants commonly died early after presentation, sometimes before a diagnosis of Barth syndrome was made. With increases in awareness of Barth syndrome and in the care of infants with severe heart failure, survival of children with Barth syndrome and severe heart failure has improved. We describe our experience caring for five unrelated boys with Barth syndrome who presented with severe cardiomyopathy and heart failure prior to age 2 who have had marked improvement with long‐term response to medical heart failure therapy.
Systematic profiling and identification of the peptide‐mediated interactions between human Yes‐associated protein and its partners in esophageal cancer
Authors: Chen Fei , Wang Qifei , Mu Yushu , Sun Shibin , Yuan Xulong , Shang Pan , Ji Bo
Published: December 2021

Human Yes‐associated protein (YAP) is involved in the Hippo signaling pathway and serves as a coactivator to modulate gene expression, which contains a transactivation domain (TD) responsible for binding to the downstream TEA domain family (TEAD) of transcription factors and two WW1/2 domains that recognize the proline‐rich motifs (PRMs) present in a variety of upstream protein partners through peptide‐mediated interactions (PMIs). The downstream YAP TD‐TEAD interactions are closely associated with gastric cancer, and a number of therapeutic agents have been developed to target the interactions. In contrast, the upstream YAP WW1/2‐partner interactions are thought to be involved in esophageal cancer but still remain largely unexplored. Here, we attempted to elucidate the complicated PMIs between the YAP WW1/2 domains and various PRMs of YAP‐interacting proteins. A total of 106 peptide segments carrying the class I WW‐binding motif [P/L]Px[Y/P] were extracted from 22 partner candidates, which are potential recognition sites of YAP WW1/2 domains. Structural and energetic analyses of the intermolecular interactions between the domains and peptides created a systematic domain‐peptide binding profile, from which a number of biologically functional PMIs were identified and then substantiated in vitro using fluorescence spectroscopy assays. It is revealed that: (a) The sequence requirement for the partner recognition site binding to YAP WW1/2 domains is a decapeptide segment that contains a core PRM motif as well as two three‐residue extensions from each side of the motif; the core motif and extended sections are responsible for the binding stability and recognition specificity of domain‐peptide interaction, respectively. (b) There is an exquisite difference in the recognition specificity of the two domains; the LPxP and PPxP appear to more prefer WW1 than WW2, whereas the WW2 can bind more effectively to LPxY and PPxY than WW1. (c) WW2 generally exhibits a higher affinity to the panel of recognition site candidates than WW1. In addition, a number of partner peptides were found as promising recognition sites of the two domains and/or to have a good selectivity between the two domains. For example, the DVL1 peptide was determined to have moderate affinity to WW2 and strong selectivity for WW2 over WW1. Hydrogen bonds play a central role in selectivity.
Epidemiology of influenza under the coronavirus disease 2019 pandemic in Nanjing, China
Authors: Wu Kangjun , Wu Xiaoqing , Wang Weixiang , Hong Lei
Published: December 2021

Purpose

Since the pandemic of coronavirus disease‐19 (COVID‐19), the incidence of influenza has decreased significantly, but there are still few reports in the short period before and after the pandemic period. This study aimed to explore influenza activity and dynamic changes before and during the pandemic.

Methods

A total of 1 324 357 influenza‐like illness (ILI) cases were reported under the ILI surveillance network from January 1, 2018, to September 5, 2021, in Nanjing, of which 16 158 cases were detected in a laboratory. Differences in ILI and influenza were conducted with the χ2 test.

Results

The number of ILI cases accounted for 8.97% of outpatient and emergency department visits. The influenza‐positive ratio (IPR) was 7.84% in ILI cases. During the COVID‐19 pandemic, ILI% and IPR dropped by 6.03% and 11.83% on average, respectively. Besides this, IPR rose slightly in Week 30–35 of 2021. Not only differences in gender, age, and employment status, but also the circulating strains had changed from type A to B through the COVID‐19 pandemic.

Conclusion

The level of influenza activity was severely affected by COVID‐19, but it seems that it is inevitable to be vigilant against the co‐circulation in the future.
The emerging roles of the CDK/cyclin complexes in antiviral innate immunity
Authors: Zheng Chunfu , Tang Yan‐Dong
Published: December 2021

More than 20 members of the human cyclin‐dependent kinases (CDKs) family share the feature of being activated by cyclins. CDKs have been involved in diverse biological processes, such as cell cycle, transcription, DNA damage response, and apoptosis. If CDKs are not properly regulated, they can cause diseases like cancer. CDKs are Ser/Thr kinases that work with cyclins to control cell cycle progression. Various CDK‐cyclin complexes phosphorylate particular target proteins and drive different cell cycle stages. Accumulating evidence demonstrated that CDKs play an essential role in the cell cycle; however, their roles in antiviral innate immunity are just emerging. This minireview summarizes how CDKs play their roles in antiviral innate immunity. Our goal is to draw attention to the involvement of CDKs in antiviral innate immunity, whether as separate entities or as components of CDK/cyclin complexes that have gotten less attention in the past.
New insights into cave hyena ethology and the implications for territorial competition with hominins in Late Pleistocene north‐west Europe: the case of Caverne Marie‐Jeanne (Belgium)
Authors: Jimenez Elodie‐Laure , GERMONPRÉ MIETJE , BOUDIN MATHIEU
Published: December 2021

Megacarnivore behaviours shape ecological dynamics between their prey and competitors and therefore play a key role in structuring ecosystems. In Late Pleistocene Eurasia, hominins and hyenas were sympatric predators. Since the first discoveries of Crocuta c. spelaea in the 19th century, this ‘bone‐crushing’ species has been identified at most Palaeolithic sites and has inspired many taphonomic studies. Nonetheless, there is still very little known about its reproductive, social and spatial behaviours. We believe that exploring the complexity of the cave hyena's ethology is a way to better understand spatial relationships and niche sharing/partitioning between hominins and other top predators in Pleistocene ecosystems. This paper focuses on the study of Caverne Marie‐Jeanne Layer 4 (Hastière, Belgium), one of the best‐preserved palaeontological sites in the region. The exceptional number of hyena neonates in this assemblage (minimum number of individuals >300) has led us to describe, for the first time, a Late Pleistocene hyena birth den that was reused over a long period of time around 47.6–43k a
bp. By bridging the gap between archaeology and palaeontology, we explore the potential of carnivore socio‐spatial organisation and denning habits as an ecological proxy and discuss how these new unique data could help us further understand hominins’ spatial strategy in southern Belgium.
Mineralogy of the RBT 04262 Martian meteorite as determined by micro‐Raman and micro‐X‐ray fluorescence spectroscopies
Authors: Huidobro Jennifer , Aramendia Julene , García‐Florentino Cristina , Ruiz‐Galende Patricia , Torre‐Fdez Imanol , Castro Kepa , Arana Gorka , Madariaga Juan Manuel
Published: December 2021

Martian meteorites and terrestrial analogs represent the only samples available on Earth for studying mineralogy features of our neighbor planet Mars. This work characterizes the Roberts Massif (RBT) 04262 Martian meteorite by using mainly Raman spectroscopy. By means of this technique, it was confirmed that the meteorite matrix is composed by pyroxene and plagioclase (converted to maskelynite due to the shock pressure). Olivine‐coarse grains embedded in the matrix were also observed. These grains were coated by hydrated magnesium and calcium sulfates, which would belong to the Mars sulfate deposits or to the terrestrial weathering. Although the sulfates could be formed on Mars due to the oxidation of sulfides or elemental sulfur along the sulfur Mars cycle, their distribution along cracks and fractures confirm that are weathering products. However, other S‐bearing compounds that belong to Mars were found, such as elemental sulfur and a thermally transformed iron sulfide. Finally, the calcium phosphate merrillite and titanomagnetite were also detected. Taking this into account, the minerals found were classified into primary minerals that belong to Mars (pyroxene, olivine, elemental sulfur, and titanomagnetite), secondary ones that are alteration products of the primary minerals (maskelynite, iron sulfide, and merrillite), and terrestrial weathering products (sulfates gypsum and epsomite).
Surgical treatment of gastric adenocarcinoma: Are we achieving textbook oncologic outcomes for our patients?
Authors: Spolverato Gaya , Paro Alessandro , Capelli Giulia , Dalmacy Djhenne , Poultsides George A. , Fields Ryan C. , Weber Sharon M. , Votanopoulos Konstantinos I. , He Jin , Maithel Shishir K. , Pucciarelli Salvatore , Pawlik Timothy M.
Published: December 2021

Background and objectives

Composite measures are increasingly used to assess quality of care in surgical oncology. We sought to define the incidence of “textbook oncologic outcome” (TOO) following resection of gastric adenocarcinoma among a large, international cohort of patients.

Methods

Gastric adenocarcinoma patients undergoing resection between 2000 and 2020 were identified from an international database. TOO was defined as margin‐negative resection, examination of ≥16 lymph nodes, no prolonged length‐of‐stay (LOS), no 30‐day mortality, and stage‐appropriate receipt of chemotherapy.

Results

Among a total of 910 patients, 321 patients (35.3%) achieved a postoperative TOO. While failure to evaluate ≥16 lymph nodes (n = 591, 65.0%) and receipt of chemotherapy (n = 651, 71.5%) had the greatest negative impact on the ability to obtain a TOO, no 30‐day mortality (n = 880, 96.7%), margin‐negative resection (n = 831, 91.3%), and no extended LOS (n = 706, 77.6%) were more commonly achieved. No postoperative complications (OR: 0.44; 95% CI: 0.31−0.63) and T1a/T1b‐stage disease (OR: 2.87; 95% CI: 1.59−5.18) were independently associated with achieving a TOO (p < 0.05). The odds of achieving a TOO improved over time (p‐trend < 0.05), which was largely attributable to improved odds of evaluating ≥16 lymph nodes (2010−2014 vs. 2000−2004: OR, 5.21; 95% CI: 3.22−8.45).

Conclusions

Only about one in three patients achieved a TOO following resection of gastric adenocarcinoma. Odds of TOO increased over time, largely due to improved lymph node evaluation.
High concordance of 70‐gene recurrence risk signature and 80‐gene molecular subtyping signature between core needle biopsy and surgical resection specimens in early‐stage breast cancer
Authors: Crozier Jennifer A. , Barone Julie , Whitworth Pat , Cheong Abraham , Maganini Robert , Tamayo Jose Perez , Dauer Patricia , Wang Shiyu , Audeh William , Glas Annuska M.
Published: December 2021

Background and Objectives

With increased neoadjuvant therapy recommendations for early‐stage breast cancer patients due to the COVID‐19 pandemic, it is imperative that molecular diagnostic assays provide reliable results from preoperative core needle biopsies (CNB). The study objective was to determine the concordance of MammaPrint and BluePrint results between matched CNB and surgical resection (SR) specimens.

Methods

Matched tumor specimens (n = 121) were prospectively collected from women enrolled in the FLEX trial (NCT03053193). Concordance is reported using overall percentage agreement and Cohen's kappa coefficient. Correlation is reported using Pearson correlation coefficient.

Results

We found good concordance for MammaPrint results between matched tumor samples (90.9%, κ = 0.817), and a very strong correlation of MammaPrint indices (r = 0.94). The concordance of BluePrint subtyping in matched samples was also excellent (98.3%).

Conclusions

CNB samples demonstrated high concordance with paired SR samples for MammaPrint risk classification and BluePrint molecular subtyping, suggesting that physicians are provided with accurate prognostic information that can be used to guide therapy decisions.
Pleuropulmonary Ultrasound in Pediatrics: Proposal of a Reporting Model From the Academy of Thoracic Ultrasound
Authors: Amendolea Antonella , Gori Laura , Adamoli Paolo , Limoli Giuseppe , Supino Maria Chiara , Coco Alfina Domenica , Trobia Gian Luca , Tursi Francesco , Soldati Gino , Buonsenso Danilo ,   Gruppo di studio Pediatrico AdET
Published: December 2021

With the emergence of the Covid‐19 pandemic, pleuropulmonary ultrasound has become a very common tool in clinical practice, even in the pediatric field. Therefore, the clinicians' need to speak a common ultrasound language becomes increasingly necessary. The Italian scientific society AdET (Academy of Thoracic Ultrasound) has been carrying out the study and dissemination of pulmonary ultrasound in medical practice in Italy for years. With this article, the pediatric AdET group wants to propose a report model of pediatric pulmonary ultrasound as a useful tool in daily clinical practice to interpret the images and reach a diagnostic conclusion, aiming to share a standardized approach that may also support the sharing of research findings.
Interobserver Agreement and Correlation of an Automated Algorithm for B‐Line Identification and Quantification With Expert Sonologist Review in a Handheld Ultrasound Device
Authors: Moore Christopher L. , Wang Jing , Battisti Anthony J. , Chen Alvin , Fincke Jonathan , Wang Anita , Wagner Michael , Raju Balasundar , Baloescu Cristiana
Published: December 2021

Objectives

B‐lines are ultrasound artifacts that can be used to detect a variety of pathologic lung conditions. Computer‐aided methods to detect and quantify B‐lines may standardize quantification and improve diagnosis by novice users. We sought to test the performance of an automated algorithm for the detection and quantification of B‐lines in a handheld ultrasound device (HHUD).

Methods

Ultrasound images were prospectively collected on adult emergency department patients with dyspnea. Images from the first 124 patients were used for algorithm development. Clips from 80 unique subjects for testing were randomly selected in a predefined proportion of B‐lines (0 B‐lines, 1–2 B‐lines, 3 or more B‐lines) and blindly reviewed by five experts using both a manual and reviewer‐adjusted process. Intraclass correlation coefficient (ICC) and weighted kappa were used to measure agreement, while an a priori threshold of an ICC (3,k) of 0.75 and precision of 0.3 were used to define adequate performance.

Results

ICC between the algorithm and manual count was 0.84 (95% confidence interval [CI] 0.75–0.90), with a precision of 0.15. ICC between the reviewer‐adjusted count and the algorithm count was 0.94 (95% CI 0.90–0.96), and the ICC between the manual and reviewer‐adjusted counts was 0.94 (95% CI 0.90–0.96). Weighted kappa was 0.72 (95% CI 0.49–0.95), 0.88 (95% CI 0.74–1), and 0.85 (95% CI 0.89–0.96), respectively.

Conclusions

This study demonstrates a high correlation between point‐of‐care ultrasound experts and an automated algorithm to identify and quantify B‐lines using an HHUD. Future research may incorporate this HHUD in clinical studies in multiple settings and users of varying experience levels.
Assessment of land use systems for CO2 sequestration, carbon credit potential, and income security in Vindhyan region, India
Authors: Roy Oindrila , Meena Ram Swaroop , Kumar Sandeep , Jhariya Manoj Kumar , Pradhan Gourisankar
Published: December 2021

Land‐use systems (LUSs) in the agriculture urgently need to be revised to reduce greenhouse gases emissions (GHGs), and promote long‐term sustainability. This study aimed to estimate the highest amount of CO2 sequestration, carbon (C) stocks, and credit potential to mitigate climate change, and importantly identify a more sustainable LUS for income security, which can be easily adopted by farmers. The experiment was executed with the current year six LUSs: (1) legumes cereal wheat (Triticum aestivum) ‐based LUS (LCBLUS); (2) vegetable (cabbage ‐Brassica oleracea varcapitata) ‐based LUS (VBLUS) (farmer field); (3) guava (Psidium guajava) + linseed (Linum usitatissimum) ‐based LUS (GLBLUS); (4) custard apple (Annona reticulata) + barley (Hordeum vulgare) ‐based LUS (CABBLUS); (5) bael (Aegle marmelos) + mustard (Brassica juncea) ‐based LUS (BMBLUS), and (6) teak (Tectona grandis) ‐based forest LUS (TBFLUS) with four‐times replicated in a randomized block design (RBD). The soil samples were collected at 0–15 and 15–30 cm depths from the study area at the start, and end of the experiment. Results revealed that the mean value of a bulk density (ρb) and particle density (ρd) was ranged from 1.38–1.54 Mg m−3 and 2.40–2.65  Mg m−3, respectively. The mean value of pH and EC was ranged from 4.49–5.84 and 0.07–0.21 dsm‐1, respectively. Soil organic carbon (SOC) was ranged from 0.48%–0.76% and the total NPK stock range was from 51.69–58.97 Mgha‐1. The biomass accumulation, C stock, sequestration potential, and credit for six LUSs were ranged from 9.39–75.82, 4.69–37.91, 17.23–139.93  Mgha‐1, and 689–5565 US$ha‐1, respectively. The highest biomass accumulation, C stock, sequestration, and credit potential were observed under TBFLUS and the lowest under LCBLUS. The highest estimated market price was 5583.14 US$ha‐1 from BMBLUS, followed by CABBLUS (5284.42 US$ha‐1), GLBLUS (5121.70 US$ha‐1), and VBLUS (4198.40 US$ha‐1). While the minimum price market price was 969.83 US$ha‐1 recorded from LCBLUS. According to the results of this experiment, the TBFLUS had the highest soil enrichment, maximum C storage, and CO2 sequestration capacity among all the LUSs.
Peptide Modified Albumin–Paclitaxel Nanoparticles for Improving Chemotherapy and Preventing Metastasis
Authors: Fu Ying , Yang Shuyan , Liu Yuning , Liu Jian , Wang Qizhi , Li Fengyan , Shang Xiuzhuan , Teng Yuou , Guo Na , Yu Peng
Published: December 2021

Metastasis and recurrence are the main causes of death in cancer patients; however, there are few medicines that can inhibit tumor growth and metastasis at the same time. In this work, a novel nano‐drug delivery system (NDDS) based on targeting ligand modified albumin is reported. The hydrophobic drug (paclitaxel) induces albumin self‐assembly after treatment of albumin with l‐cysteine, forming drug‐loaded nanoparticles with a size of 100–200 nm. Importantly, the albumin nanoparticles display enhanced antitumor efficacy against tumor growth/lung metastasis in 4T1 bearing nude mice and prevention of lung metastasis in a B16‐F10 model. This study provides a facile method for hydrophobic chemo‐drugs loaded albumin nanoparticles preparation and a promising chemotherapy with effective tumor growth inhibition and metastasis prevention.
Photo‐Crosslinking and Reductive Decrosslinking of Polymethacrylate‐Based Copolymers Containing 1,2‐Dithiolane Rings
Authors: Maes Stephan , Scholiers Vincent , Du Prez Filip E.
Published: December 2021

This study first describes a straightforward approach for the preparation of polymethacrylate‐based networks containing variable amounts of lipoates. For this purpose, butyl methacrylate and a 1,2‐dithiolane derivative of hydroxymethylmethacrylate are copolymerized in different ratios by free‐radical polymerization with the formation of linear network precursors. After optimizing the copolymerization conditions, the ultraviolet (UV)‐induced crosslinking behavior is studied. The latter is possible because of the presence of 1,2‐dithiolane moieties, which can be photolytically cleaved and recombined upon UV‐irradiation. The obtained networks are analyzed in terms of swelling degree, gel fraction, and rheological behavior. Then, network decrosslinking is achieved by immersing the networks in a reducing environment. Finally, successful preliminary coating experiments are conducted, demonstrating the potential applicability of the studied materials.
Stretchable and Thermally Responsive Semi‐Interpenetrating Nanocomposite Hydrogel for Wearable Strain Sensors and Thermal Switch
Authors: Yan Jiao , Xia Yuanmeng , Lai Jingjuan , Zhao Chunxia , Xiang Dong , Li Hui , Wu Yuanpeng , Li Zhenyu , Zhou Hongwei
Published: December 2021

Wearable electronics based on stimuli‐responsive hydrogels are promising in various applications such as soft robots, artificial skin, and health monitoring. Herein, a novel wearable and strain/thermal dual sensor is developed utilizing a nanocomposite hydrogel, which is prepared by incorporating allyl mercaptan (ALM) functionalized Au nanoparticles (Au@ALM) into poly(N‐isopropylacrylamide‐co‐hydroxyethylmethacrylate)/poly(N‐isopropylacrylamide) (P(NIPAM‐co‐HEMA)/PNIPAM) semi‐interpenetrating hydrogel network. PNIPAM acts as the thermally responsive component. Semi‐interpenetrating network and Au nanoparticles are introduced to enhance the mechanical properties of the hydrogel. Au nanoparticles also work as the electrically conductive component. Strain sensor and thermoreceptor are realized by using the mechanical stretchability and strain‐ or temperature‐dependent conductivity. The strain sensor exhibited excellent stability and repeatability in the strain range of 0–150%. Remarkably, the thermal sensor made of this hydrogel can monitor the ambient temperature from 0 to 70 °C. Therefore, an intelligent thermal switch is designed that can effectively protect electronic components by disconnecting high‐temperature circuits. The nanocomposite hydrogel holds great potential in smart devices and flexible sensors.
Pharmacologic inhibition of ataxia telangiectasia and Rad3‐related (ATR) in the treatment of head and neck squamous cell carcinoma
Authors: Karukonda Pooja , Odhiambo Diana , Mowery Yvonne M.
Published: December 2021

Head and neck squamous cell carcinoma (HNSCC) poses significant treatment challenges, with high recurrence rates for locally advanced disease despite aggressive therapy typically involving a combination of surgery, radiation therapy, and/or chemotherapy. HNSCCs commonly exhibit reduced or absent TP53 function due to genomic alterations or human papillomavirus (HPV) infection, leading to dependence on the S‐ and G2/M checkpoints for cell cycle regulation. Both of these checkpoints are activated by Ataxia Telangiectasia and Rad3‐related (ATR), which tends to be overexpressed in HNSCC relative to adjacent normal tissues and represents a potentially promising therapeutic target, particularly in combination with other treatments. ATR is a DNA damage signaling kinase that is activated in response to replication stress and single‐stranded DNA breaks, such as those induced by radiation therapy and certain chemotherapies. ATR kinase inhibitors are currently being investigated in several clinical trials as part of the management of locally advanced, recurrent, or metastatic HNSCC, along with other malignancies. In this review article, we summarize the rationale and preclinical data supporting incorporation of ATR inhibition into therapeutic regimens for HNSCC.
Conditional deletion of mTOR discloses its essential role in early B‐cell development
Authors: Zhang Shuling , Dubois Wendy , Feng Xingmin , Nguyen Joe T. , Young Neal S. , Mock Beverly A.
Published: December 2021

Mechanistic target of rapamycin (mTOR) is a serine‐threonine kinase and central regulator of cell growth, differentiation, and survival. mTOR is commonly hyperactivated in a diverse number of cancers and critical roles for mTOR in regulating immune cell differentiation and function have been demonstrated. However, there is little work investigating the roles of mTOR in early B‐cell development. Here we demonstrate that conditional disruption of mTOR in developing mouse B cells results in reduced pre‐B‐cell proliferation and survival, as well as a developmental block at the pre‐B‐cell stage, with a corresponding lack of peripheral B cells. Upon immunization with NP‐CGG antigen, mice with Mtor conditional disruption in early B cells lost their ability to form germinal centers and produce specific antibodies. In competitive BM repopulation assays, donor BM cells from conditional knock‐out mice were completely impaired in their ability to reconstitute B cells. Our data reveal the essential role of mTOR in early pre‐B‐cell development and survival.
Price premium or price discount for locally produced food products? A 5W1H approach in meta‐analysis
Authors: Yang Yiwen , Leung PingSun , Tseng Chu‐wei
Published: December 2021

Previous empirical studies reveal conflicting results of estimating the price differential between locally produced foods and their imported counterparts. This study aims to identify possible key determinants of these diverse findings under the 5W1H conceptual scaffold. We conduct a meta‐analysis of the empirical evidence on price premiums or discounts of local food, based on a sample of 80 estimates obtained from 42 studies. Our findings show that studies using actual market prices generate a lower price premium of locally produced food than those using a willingness‐to‐pay value. Furthermore, our results reflect that consumers are increasingly more interested in local food over time.
Disruption of Brainstem Structural Connectivity in REM Sleep Behavior Disorder Using 7 Tesla Magnetic Resonance Imaging
Authors: García‐Gomar María G. , Videnovic Aleksandar , Singh Kavita , Stauder Matthew , Lewis Laura D. , Wald Lawrence L. , Rosen Bruce R. , Bianciardi Marta
Published: December 2021

Background

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is one of the earliest manifestations of α synucleinopathies. Brainstem pathophysiology underlying REM sleep behavior disorder has been described in animal models, yet it is understudied in living humans because of the lack of an in vivo brainstem nuclei atlas and to the limited magnetic resonance imaging (MRI) sensitivity.

Objective

To investigate brainstem structural connectivity changes in iRBD patients by using an in vivo probabilistic brainstem nuclei atlas and 7 Tesla MRI.

Methods

Structural connectivity of 12 iRBD patients and 12 controls was evaluated by probabilistic tractography. Two‐sided Wilcoxon rank‐sum test was used to compare the structural connectivity indices across groups.

Results

In iRBD, we found impaired (Z = 2.6, P < 0.01) structural connectivity in 14 brainstem nuclei, including the connectivity between REM‐on (eg, subcoeruleus [SubC]) and REM sleep muscle atonia (eg, medullary reticular formation) areas.

Conclusions

The brainstem nuclei diagram of impaired connectivity in human iRBD expands animal models and is a promising tool to study and possibly assess prodromal synucleinopathy stages. © 2021 International Parkinson and Movement Disorder Society
Modelling of bivariate meteorological drought analysis in Lake Urmia Basin using Archimedean copula functions
Authors: Khezri Farzad , Irandoost Mohsen , Jalalkamali Navid , Yazdanpanah Najme
Published: December 2021

The Urmia Lake Basin as the world's second largest salt lake has experienced severe drought during recent years. The purpose of this study is to analyse the bivariate characteristics of drought (i.e., duration and severity) using two indices including SPI (standard precipitation index) and SPImod (modified SPI) associated with copula functions. For this purpose, rainfall data of six stations were used for the period of 1971–2017. At first, the characteristics of drought were extracted using the two indices. Then, through coding in the MATLAB software environment, eight families of Archimedean copula functions were applied. The simultaneous return period and conditional and Kendall returns were also investigated. The result showed that the Joe copula function was the best predictor for the analysis of both intensity and duration of drought for the study area. The correlation coefficients of Spearman, linear correlation and Tau Kendall computed for the SPI of stations were >0.65, >0.72 and >0.48, respectively, while all of them were significant. At a given critical probability level, t, the value of the Kendall return period was much greater than the standard return period, so that this difference increased with increasing t value. The results obtained from the time series of indices indicated that at least 40% of the months were dry, and the severity of droughts in the Urmia station was much higher than other stations during the studied period. Moreover, SPImod to a large extent eliminates the disadvantages of conventional SPI and takes into account seasonal variations of precipitation in the calculation of SPI.
Machine learning in calibrating tropical cyclone intensity forecast of ECMWF EPS
Authors: Chan Ming Hei Kenneth , Wong Wai Kin , Au‐Yeung Kin Chung
Published: December 2021

Intensity prediction of tropical cyclones (TC) has been one of the major challenges for the operational forecast and warning service, as well as consequential assessment of impacts including high winds, storm surge and heavy rainfall caused by TC. With the advances in global numerical weather prediction (NWP) modelling systems, TC track and intensity forecasts for medium range are available every 6 or 12 h, and ensemble prediction system (EPS) outputs provide various scenarios for producing probabilistic forecasts. The TC intensity forecast from the EPS of the European Centre for Medium‐Range Weather Forecasts (ECMWF) has shown systematic negative biases, although the performance is better than other global models in general. A machine learning model based on XGBoost, a decision‐tree‐based machine learning algorithm, is introduced in this paper to post‐process ECMWF EPS outputs and generate an improved forecast of TC intensity. The predictors such as selected percentiles of ensemble members in maximum wind and minimum pressure of previous TC cases were applied in the XGBoost model to generate a calibrated forecast for the maximum wind of TCs. Verification of the XGBoost model was made using TCs over the western North Pacific during 2016–2019. It is found that the negative biases of the intensity forecast from ECMWF EPS and HRES can be reduced with improvement in the overall accuracy.
A Leigh syndrome caused by compound heterozygous mutations on NDUFAF5 induce early infant death: A case report
Authors: Wen Yan , Lu Guoyan , Qiao Lina , Li Yifei
Published: December 2021

Background

The NADH:ubiquinone oxidoreductase complex assembly factor gene (NDUFAF5) has been linked to the occurrence of Leigh syndrome, but few causative mutations have been identified. Here we report a rare case of Leigh syndrome in an infant who died in the early postnatal period.

Methods

We performed whole‐exome sequencing (WES) and mutation analysis of NDUFAF5 to obtain genetic data on the patient and describe the clinical and genetic characteristics.

Results

The proband was a 2‐month‐old male infant who suffered from recurrent vomiting and persistent seizure and died at 2 months of age after early medical support and treatment. His parents reported the unexplained death of the infant's older brother at 1 year of age. WES of the patient's DNA revealed c.357C>G and c.611C>T compound heterozygous mutations in NDUFAF5; analysis with the MutationTaster application indicated that both were pathogenic (p = 0.99). Significant structural changes in the transport domain of the protein were predicted using SWISS‐MODEL. We estimated the stability of the mutant protein using a mutation cutoff scanning matrix and found reductions in Gibbs free energy (−0.623 kcal/mol for p.D119E and −0.813 kcal/mol for p.A204V), indicating that the mutations led to an unstable protein structure. We speculated that the patient died as a result of impaired mitochondrial function caused by the NDUFAF5 mutations, and made a diagnosis of Leigh syndrome.

Conclusion

Our results demonstrate that molecular genetic screening is useful for the diagnosis of mitochondrial diseases, especially in children with a positive family history. Leigh syndrome should be considered in the diagnosis of patients presenting with severe recurrent vomiting and feeding difficulties with persistent seizure. Our findings expand the mutation spectrum of the NDUFAF5 gene and contribute to the genotype–phenotype map of mitochondrial respiratory chain complex I deficiency.
Bovine Milk‐Derived Extracellular Vesicles Inhibit Catabolic and Inflammatory Processes in Cartilage from Osteoarthritis Patients
Authors: Pieters Bartijn C. H. , Arntz Onno J. , Aarts Joyce , Feitsma Anouk L. , van Neerven R. J. Joost , van der Kraan Peter M. , Oliveira Marina C. , van de Loo Fons A. J.
Published: December 2021

Scope

Data from the Osteoarthritis Initiative shows that females who drink milk regularly have less joint cartilage loss and OA progression, but the biologic mechanism is unclear. Bovine milk is a rich source of extracellular vesicles (EVs), which are small phospholipid bilayer bound structures that facilitate intercellular communication. In this study, the authors aim to evaluate whether these EVs may have the capacity to protect cartilage from osteoarthritis patients, ex vivo, by directly effecting chondrocytes.

Methods and Results

Human cartilage explants are exposed to cow's milk‐derived EVs (CMEVs), which results in reduced sulfated glycosaminoglycan release and inhibition of metalloproteinase‐1 expression. Incubation of articular chondrocytes with CMEVs also effectively reduces expression of cartilage destructive enzymes (ADAMTS5, MMPs), which play key roles in the disease progression. In part, these findings are attributed to the presence of TGFβ on these vesicles, and in addition, a possible role is reserved for miR‐148a, which is functionally transferred by CMEVs.

Conclusion

These findings highlight the therapeutic potential of local CMEV delivery in osteoarthritic joints, where inflammatory and catabolic mediators are responsible for joint pathology. CMEVs are carriers of both TGFβ and miR‐148a, two essential regulators for maintaining chondrocyte homeostasis and protection against cartilage destruction.
An opto‐electronic oscillator based on Fabry‐Perot stabilized dual‐wavelength fiber ring laser
Authors: Correia Marlon , Tovar Pedro , Ribeiro Ricardo M. , von der Weid Jean Pierre
Published: December 2021

The authors experimentally demonstrate an opto‐electronic oscillator based on a dual‐wavelength fiber ring laser with an inline specially designed fiber‐Bragg‐grating‐based Fabry‐Perot filter. An erbium‐doped fiber amplifier initiates the process as a broadband light source while a second optical amplifier provides additional gain to increase the cavity power. By exploiting the two‐wavelength beating, a 10.3 GHz microwave carrier with 3‐dB linewidth of <200 Hz was generated with 77 dB signal‐to‐noise ratio. Phase noise of −100 dBc/Hz @10 kHz offset is achieved, which is very appropriate for microwave applications in X‐band that often require high extinction ratio and low phase noise.
Improving predictive CTV segmentation on CT and CBCT for cervical cancer by diffeomorphic registration of a prior
Authors: Beekman Chris , van Beek Suzanne , Stam Jikke , Sonke Jan‐Jakob , Remeijer Peter
Published: December 2021

Purpose

Automatic cervix‐uterus segmentation of the clinical target volume (CTV) on CT and cone‐beam CT (CBCT) scans is challenged by the limited visibility and the non‐anatomical definition of certain border regions. We study the potential performance gain of convolutional neural networks by regulating the segmentation predictions as diffeomorphic deformations of a segmentation prior.

Materials and Methods

We introduce a 3D convolutional neural network that segments the target scan by joint voxel‐wise classification and the registration of a given prior. We compare this network to two other 3D baseline models: One treating segmentation as a classification problem (segmentation‐only), the other as a registration problem (deformation‐only). For reference and to highlight the benefits of a 3D model, these models are also benchmarked against a 2D segmentation model. Network performances are reported for CT and CBCT segmentation of the cervix‐uterus CTV. We train the networks on the data of 84 patients. The prior is provided by the CTV segmentation of a planning CT. Repeat CT or CBCT scans constitute the target scans to be segmented.

Results

All 3D models outperformed the 2D segmentation model. For CT segmentation, combining classification and registration in the proposed joint model proved beneficial, achieving a Dice score of 0.87 and a mean squared error (MSE) of the surface distance below 1.7 mm. No such synergy was observed for CBCT segmentation, for which the joint and the deformation‐only model performed similarly, achieving a Dice score of about 0.80 and an MSE surface distance of 2.5 mm. However, the segmentation‐only model performed notably worse in this low contrast regime. Visual inspection revealed that this performance drop translated into geometric inconsistencies between the prior and target segmentation. Such inconsistencies were not observed for the deformation‐based models.

Conclusion

Constraining the solution space of admissible segmentation predictions to those reachable by a diffeomorphic deformation of the prior proved beneficial as it improved geometric consistency. Especially for CBCT, with its poor soft‐tissue contrast, this type of regularization becomes important as shown by quantitative and qualitative evaluation.
Technical note: Bremsstrahlung dose in the electron beam at extended distances in total skin electron therapy
Authors: Ding George X. , Kucuker‐Dogan Serpil , Das Indra J.
Published: December 2021

Purpose

Electron beam from a linear accelerator is commonly used in total skin electron therapy (TSET) at extended distances. Since Das et al (Med Phys 21, p.1733, 1994) reported 5% bremsstrahlung dose for a 6 MeV electron beam at extended distance of 500 cm it has been accepted as common knowledge. However, measurements by Chen et al (Int J. Rad Onc Biol Phys 59 p.872, 2004) and Monte Carlo simulations by Ding et al (Phys. Med. Biol. 66, 075010, 2021) were unable to reproduce such high bremsstrahlung dose. As bremsstrahlung dose contributes to whole‐body dose, which could produce bone marrow toxicity with serious complications for the outcome of the TSET, it is important to re‐evaluate the magnitude of bremsstrahlung dose accurately.

Methods

The EGSnrc Monte Carlo system is used to investigate bremsstrahlung doses from 6 MeV high dose rate total skin electron (HDTSe) beams from Varian TrueBeam and Clinac Accelerators. The measurements were carried out at a depth of dmax and 5 cm in Solid Water and Acrylic phantoms at extended distances using a parallel‐plate chamber and a cylindrical ion chamber.

Results

We were able to reproduce previously reported high bremsstrahlung dose at extended distances by using a parallel plate ionization chamber. However, both the measurements made by using a cylindrical chamber and Monte Carlo simulations showed an insignificant bremsstrahlung dose (∼1%) even at SSD = 500 cm.

Conclusion

The bremsstrahlung doses of a 6 MeV electron beam are 0.5% to 1% for SSD from 100 to 700 cm, although it increases with the increasing extended distance. The common belief of up to 5% bremsstrahlung dose at large extended distances is incorrect. Previously reported high bremsstrahlung doses might be due to poor signal‐to‐noise ratio of using a parallel plate chamber for measuring very low dose or particular setup.
Assessing the accuracy of electronic portal imaging device (EPID)‐based dosimetry: I. Quantities influencing long‐term stability
Authors: Renaud James , Muir Bryan
Published: December 2021

Purpose

The aim of this study is to reduce the uncertainty associated with determining dose‐to‐water using an amorphous silicon electronic portal imaging detector (EPID) under reference conditions by identifying and accounting for operational and environmental factors influencing the long‐term stability of EPID response.

Methods

Measurements of the EPID relative response, corrected for variations in linear accelerator (linac) output, were performed regularly over a period of 12 months. For every acquired image set, measurements of detector supply voltages, internal operating temperature, and ambient environmental conditions were obtained. Pearsonrcorrelation coefficients were then calculated for each pair of variables, a subset of which were fitted using multiple linear regression to develop a predictive model of EPID response. Principal component analysis was performed on the dataset to reveal the internal structure of the data in a way that best accounts for the observed variations.

Results

The +5.5 V power supply voltage, internal operating temperature, and the accumulated dose absorbed in EPID were identified as having the greatest influence on the long‐term stability of EPID response. By correcting for the combined effect of these variables, the mean difference in linac output as measured by the EPID relative to a reference class chamber improved from ‐0.46% to 0.23% over the period of the study.

Conclusions

This work suggests that the stability of an EPID over a period of a year can be improved by a factor of two by monitoring and accounting for the effects of variations in power supply voltage, internal temperature of the detector, and accumulated absorbed dose.
Quantitative MRI analysis of structural changes in tomato tissues resulting from dehydration
Authors: Leforestier Rodolphe , Fleury Anna , Mariette François , Collewet Guylaine , Challois Sylvain , Musse Maja
Published: December 2021

A quantitative magnetic resonance imaging (MRI) analysis at 1.5T of the effects of different dehydration regimes on transverse relaxation parameters measured in tomato tissue is presented. Multi‐exponential T2 maps have been estimated for the first time, providing access to spatialized microstructural information at voxel scale. The objective was to provide a better understanding of the changes in the multi‐exponential transverse relaxation parameters induced by dehydration in tomato tissues and to unravel the effects of microstructure and composition on relaxation parameters. The results led to the hypothesis that the multi‐exponential relaxation signal reflects cell compartmentation and tissue heterogeneity, even at the voxel scale. Multi‐exponential relaxation times provided information about water loss from specific cell compartments and seem to indicate that the dehydration process mainly affects large cells. By contrast, total signal intensity showed no sensitivity to variations in water content in the range investigated in the present study (between 95% [fresh tissue] and 90% [after dehydration]). The variation in relaxation times resulting from water loss was due to both changes in solute concentration and compartment size. The comparative analysis of the two contrasted tissues in terms of microporosity demonstrated that magnetic susceptibility effects, caused by the presence of air in the placenta tissue, significantly impact the effective relaxation and might be the dominant effect in the variations observed in relaxation times in this tissue.