bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbonates from the ancient world's longest aqueduct: A testament of Byzantine water management
Authors: Sürmelihindi Gül , Passchier Cees , Crow James , Spötl Christoph , Mertz‐Kraus Regina
Published: May 2021

The fourth‐ and fifth‐century aqueduct system of Constantinople is, at 426 km, the longest water supply line of the ancient world. Carbonate deposits i659ide an archive of both archaeological developments and palaeo‐environmental conditions during the depositional period. The 246‐km‐long aqueduct line from the fourth century used springs from a small aquifer, whereas a 180‐km‐long fifth‐century extension to the west tapped a larger aquifer. Although historical records testify at least 700 years of aqueduct activity, carbonate deposits in the aqueduct system display less than 27 years of operation. This implies that the entire system must have been cleaned of carbonate, presumably during regular campaigns. A 50‐km‐long double‐aqueduct section in the central part of the system may have been a costly but practical solution to allow repairs and cleaning of the aqueducts of carbonate to ascertain a continuous water supply to the city. The fifth‐century channel was commonly contaminated with clay, caused by the nature of the aqueduct system and possible local damage to the channel. This clay‐rich water could have been one of the reasons for the construction of large reservoirs in Constantinople.

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Oligodendrocyte progenitor cell maturation is dependent on dual function of MCT8 in the transport of thyroid hormone across brain barriers and the plasma membrane
Authors: Vatine Gad D. , Shelest Oksana , Barriga Bianca K. , Ofan Raz , Rabinski Tatyana , Mattis Virginia B. , Heuer Heike , Svendsen Clive N.
Published: May 2021

Inactivating mutations in the thyroid hormone (TH) transporter monocarboxylate transporter 8 (MCT8) causes a rare and debilitating form of X‐linked psychomotor disability known as Allan Herndon Dudley syndrome (AHDS). One of the most prominent pathophysiological symptoms of MCT8‐deficiency is hypomyelination. Here, patient‐derived induced pluripotent stem cells (iPSCs) were used to study the role of MCT8 and TH on the maturation of oligodendrocytes. Interestingly, neither MCT8 mutations nor reduced TH affected the in vitro differentiation of control or MCT8‐deficient iPSCs into oligodendrocytes. To assess whether patient‐derived iPSC‐derived oligodendrocyte progenitor cells (iOPCs) could provide myelinating oligodendrocytes in vivo, cells were transplanted into the shiverer mouse corpus callosum where they survived, migrated, and matured into myelinating oligodendrocytes, though the myelination efficiency was reduced compared with control cells. When MCT8‐deficient and healthy control iOPCs were transplanted into a novel hypothyroid immunodeficient triple knockout mouse (tKO, mct8−/−; oatp1c1−/−; rag2−/−), they failed to provide behavioral recovery and did not mature into oligodendrocytes in the hypothyroid corpus callosum, demonstrating the critical role of TH transport across brain barriers in oligodendrocyte maturation. We conclude that MCT8 plays a cell autonomous role in oligodendrocyte maturation and that functional TH transport into the central nervous system will be required for developing an effective treatment for MCT8‐deficient patients.
Network interdigitations of Tau and amyloid‐beta deposits define cognitive levels in aging
Authors: Kim Chan‐Mi , Montal Victor , Diez Ibai , Orwig William ,   Alzheimer's Disease Neuroimaging Initiative (ADNI), Sepulcre Jorge
Published: May 2021

Amyloid‐beta (Aβ) plaques and tau neurofibrillary tangles are pathological hallmarks of Alzheimer's disease (AD); their contribution to neurodegeneration and clinical manifestations are critical in understanding preclinical AD. At present, the mechanisms related to Aβ and tau pathogenesis leading to cognitive decline in older adults remain largely unknown. Here, we examined graph theory‐based positron emission tomography (PET) analytical approaches, within and between tau and Aβ PET modalities, and tested the effects on cognitive changes in cognitively normal older adults (CN). Particularly, we focused on the network interdigitations of Aβ and tau deposits, along with cognitive test scores in CN at both baseline and 2‐year follow‐up (FU). We found highly significant Aβ‐tau network integrations in AD vulnerable areas, as well as significant associations between those Aβ‐tau interdigitations and general cognitive impairment in CN at baseline and FU. Our findings suggest a distinctive contribution of interlinking network relationships between Aβ and tau deposits in heteromodal areas of the human brain. They support a network‐based interaction between Aβ and tau accumulations as a key factor for cognitive deterioration in CN prior to dementia.
Distributed functional connectivity predicts neuropsychological test performance among older adults
Authors: Kwak Seyul , Kim Hairin , Kim Hoyoung , Youm Yoosik , Chey Jeanyung
Published: May 2021

Neuropsychological test is an essential tool in assessing cognitive and functional changes associated with late‐life neurocognitive disorders. Despite the utility of the neuropsychological test, the brain‐wide neural basis of the test performance remains unclear. Using the predictive modeling approach, we aimed to identify the optimal combination of functional connectivities that predicts neuropsychological test scores of novel individuals. Resting‐state functional connectivity and neuropsychological tests included in the OASIS‐3 dataset (n = 428) were used to train the predictive models, and the identified models were iteratively applied to the holdout internal test set (n = 216) and external test set (KSHAP, n = 151). We found that the connectivity‐based predicted score tracked the actual behavioral test scores (r = 0.08–0.44). The predictive models utilizing most of the connectivity features showed better accuracy than those composed of focal connectivity features, suggesting that its neural basis is largely distributed across multiple brain systems. The discriminant and clinical validity of the predictive models were further assessed. Our results suggest that late‐life neuropsychological test performance can be formally characterized with distributed connectome‐based predictive models, and further translational evidence is needed when developing theoretically valid and clinically incremental predictive models.
Place of birth for unintended pregnancies in six former Soviet Union countries
Authors: Bellizzi Saverio , Pichierri Giuseppe , Panu Napodano Catello M , Murgia Paola , Padrini Susanna , Bassat Quique
Published: May 2021

Objective

This paper aims at exploring the association between unintended pregnancies and place of birth in six Former Soviet Union (FSU) countries.

Material and methods

A secondary analysis of the latest cross‐sectional Demographic and Health Surveys of six FSU countries from 2005 through 2012 was conducted. Prevalence of institutional births and unintended pregnancies was estimated by country and for the pooled population. Odds ratio (OR) and 95% confidence interval (CI) were calculated to measure the country and pooled association between pregnancy intention and institutional birth.

Results

Institutional births occurred in 90.4% of the overall study population and ranged from 78.2% in Tajikistan to 99.7% in Ukraine Demographic and Health Survey. Around one out of 10 pregnancies resulted unintended. In the pooled analysis, unintended pregnancies were significantly associated with giving births outside health facility (aOR1.2; 95% CI 1.0–1.6).

Conclusion

Based on the study findings we suggest that increase awareness of benefit of skilled delivery care is needed among women with poor access to family planning.
Hair today, gone tomorrow: How personal protective equipment guidance changed doctor's facial hair during the COVID‐19 pandemic
Authors: Sahota Sanjeev , Gill Simon , Ridenton Jennifer , Hegarty Helen , Pope Katherine , Gentile Giorgio
Published: May 2021

Objectives

To investigate how personal protective equipment (PPE) guidance altered the facial hair of hospital doctors and explore the wider impact and implications of these changes.

Methods

A single site uncontrolled before‐after survey study examining change in facial hairstyles, and wider implications on doctor's cultural, religious, and personal wellbeing. Outcome measures included change in facial hair between January and April 2020 and whether these changes adhered to guidance set by Public Health England. Participants were also asked about the wider impact of these changes which were thematically analyzed using an inductive approach.

Results

Of those who completed the survey, 257 participants met the inclusion criteria. 68% (n = 67) of doctors who could grow facial hair changed their facial hairstyle during the COVID‐19 pandemic and 96% (n = 64) reported that the change was in response to PPE guidance. The odds of having a facial hairstyle that complied with PPE guidance before the pandemic was 0.32, which rose to 2.77 after guidance was released, giving an odds ratio of 8.54 (95% CI 4.49‐16.23, P < .001). When compared to those who sported a shaven face prepandemic, the odds ratio of a change in style for those with prepandemic full beards was 37.92 (95% CI 7.45‐192.8, P < .001), for goatees was 7.22 (95% CI 1.076‐48.47, P = .04), for moustaches was 4.33 (95% CI 0.207‐90.85, P = .345), and for stubble was 9.06 (95% CI 2.133‐38.49, P = .003). Qualitative analysis revealed multiple themes, including skin irritation, loss of identity, and a significant impact on participants required to maintain a beard due to religious or cultural reasons.

Conclusions

Facial hairstyles have changed significantly at our hospital during the COVID‐19 pandemic. Facial hair can impact upon doctors' cultural, religious, and personal wellbeing and these factors need to be considered with policy and provision of PPE.
Effectiveness of peer‐supervision on pediatric fever illness treatment among registered private drug sellers in East‐Central Uganda: An interrupted time series analysis
Authors: Bagonza Arthur , Kitutu Freddy Eric , Peterson Stefan , Mårtensson Andreas , Mutto Milton , Awor Phyllis , Mukanga David , Wamani Henry
Published: May 2021

Rationale, aims, and objectives

Appropriate treatment of pediatric fever in rural areas remains a challenge and maybe partly due to inadequate supervision of licensed drug sellers. This study assessed the effectiveness of peer‐supervision among drug sellers on the appropriate treatment of pneumonia symptoms, uncomplicated malaria, and non‐bloody diarrhea among children less than 5 years of age in the intervention (Luuka) and comparison (Buyende) districts, in East‐Central Uganda.

Methods

Data on pneumonia symptoms, uncomplicated malaria, and non‐bloody diarrhea among children less than 5 years of age was abstracted from drug shop sick child registers over a 12‐month period; 6 months before and 6 months after the introduction of peer‐supervision. Interrupted time series were applied to determine the effectiveness of the peer‐supervision intervention on the appropriate treatment of pneumonia, uncomplicated malaria, and non‐bloody diarrhea among children less than 5 years of age attending drug shops in East Central Uganda.

Results

The proportion of children treated appropriately for pneumonia symptoms was 10.84% (P < .05, CI = [1.75, 19.9]) higher, for uncomplicated malaria was 1.46% (P = .79, CI = [−10.43, 13.36]) higher, and for non‐bloody diarrhea was 4.00% (P < .05, CI = [−7.95, −0.13]) lower in the intervention district than the comparison district, respectively.

Post‐intervention trend results showed an increase of 1.21% (P = .008, CI = [0.36, 2.05]) in the proportion appropriately treated for pneumonia symptoms, no difference in appropriate treatment for uncomplicated malaria, and a reduction of 1% (P < .06, CI = [−1.95, 0.02]) in the proportion of children appropriately treated for non‐bloody diarrhea, respectively.

Conclusions

Peer‐supervision increased the proportion of children less than 5 years of age that received appropriate treatment for pneumonia symptoms but not for uncomplicated malaria and non‐bloody diarrhea. Implementation of community‐level interventions to improve pediatric fever management should consider including peer‐supervision among drug sellers.
A longer‐term perspective on soil moisture, groundwater and stream flow response to the 2018 drought in an experimental catchment in the Scottish Highlands
Authors: Soulsby Chris , Scheliga Bernhard , Neill Aaron , Comte Jean‐Christophe , Tetzlaff Doerthe
Published: May 2021

The drought of summer 2018, which affected much of Northern Europe, resulted in low river flows, biodiversity loss and threats to water supplies. In some regions, like the Scottish Highlands, the summer drought followed two consecutive, anomalously dry, winter periods. Here, we examine how the drought, and its antecedent conditions, affected soil moisture, groundwater storage, and low flows in the Bruntland Burn; a sub‐catchment of the Girnock Burn long‐term observatory in the Scottish Cairngorm Mountains. Fifty years of rainfall‐runoff observations and long‐term modelling studies in the Girnock provided unique contextualisation of this extreme event in relation to more usual summer storage dynamics. Whilst summer precipitation in 2018 was only 63% of the long‐term mean, soil moisture storage across much of the catchment were less than half of their summer average and seasonal groundwater levels were 0.5 m lower than normal. Hydrometric and isotopic observations showed that ~100 mm of river flows during the summer (May‐Sept) were sustained almost entirely by groundwater drainage, representing ~30% of evapotranspiration that occurred over the same period. A key reason that the summer drought was so severe was because the preceding two winters were also dry and failed to adequately replenish catchment soil moisture and groundwater stores. As a result, the drought had the biggest catchment storage deficits for over a decade, and likely since 1975–1976. Despite this, recovery was rapid in autumn/winter 2018, with soil and groundwater stores returning to normal winter values, along with stream flows. The study emphasizes how long‐term data from experimental sites are key to understanding the non‐linear flux‐storage interactions in catchments and the “memory effects” that govern the evolution of, and recovery from, droughts. This is invaluable both in terms of (a) giving insights into hydrological behaviours that will become more common water resource management problems in the future under climate change and (b) providing extreme data to challenge hydrological models.
PAQR3 inhibits proliferation and aggravates ferroptosis in acute lymphoblastic leukemia through modulation Nrf2 stability
Authors: Jin Ling , Tong Laigen
Published: May 2021

Introduction

Acute lymphoblastic leukemia (ALL) is a usual hematological tumor, which was featured by malignant proliferation of lymphoid progenitor cells. Many important factors participate into the regulation of ALL, including proteins. PAQR3 (also named RKTG) has been proved to take part in many human cancers by acting as a tumor suppressor. PAQR3 has bee n shown to repress human leukemia cells proliferation and induce cell apoptosis, but its role and relevant regulatory mechanism on cell proliferation and ferroptosis in ALL needs more exploration.

Methods

The genes expression was detected through quantitative reverse transcription polymerase chain reaction (mRNA) or western blot (protein). The cell proliferation was assessed through Cell Counting Kit‐8 and 5‐ethynyl‐2‐deoxyuridine assays. The levels of MDA, DCF, and intracellular free Fe in ALL cells were tested through the commercial kits. The cell apoptosis was determined through flow cytometry analysis. The binding ability of PAQR3 and nuclear factor erythroid 2‐related factor 2 (Nrf2) was verified through pull down assay.

Results

PAQR3 expression was firstly assessed in ALL patients and cell lines, and discovered to be downregulated. It was verified that PAQR3 suppressed ALL cells proliferation. Further experiments proved that PAQR3 aggravates ferroptosis in ALL. In addition, AQR3 bound with Nrf2, and modulated its expression through ubiquitination in ALL. Finally, through rescue assays, it was demonstrated that Nrf2 overexpression reversed the effects of PAQR3 on cell proliferation and ferroptosis.

Conclusion

Findings from our work uncovered that PAQR3 inhibited proliferation and aggravated ferroptosis in ALL through modulation Nrf2 stability. This study suggested that PAQR3 may serve as an effective biological marker for ALL treatment.
Parameters associated with diagnosis of COVID‐19 in emergency department
Authors: Ucciferri Claudio , Caiazzo Luca , Di Nicola Marta , Borrelli Paola , Pontolillo Michela , Auricchio Antonio , Vecchiet Jacopo , Falasca Katia
Published: May 2021

Objectives

We designed this study to identify laboratory and radiological parameters, which could be useful to guide the clinician, in the evaluation of a suspected case of coronavirus disease 19 (COVID‐19).

Methods

This retrospective, observational, single‐center‐study recruited patients with a suspect of COVID‐19 data were extracted from electronic medical records using a standardized data collection form.

Results

A total of 566 patients with suspect COVID‐19 infection were enrolled (280 were COVID‐19+). The COVID‐19 population was characterized with bilateral‐pneumonia, a lower count of neutrophil, lymphocyte and monocyte, a lower neutrophil to lymphocyte‐ratio (NLR). Lower of platelet count, d‐dimer, troponin I, and serum calcium were in COVID‐19 patients. The occurrence of COVID‐19 diagnosis increased, independently of other variables, with pneumonia (odds ratio [OR]: 3.60; p < .001), neutrophil below normal range (OR: 4.15; p < .05), lactate dehydrogenase (OR: 2.09; p < .01) and sodium above normal range (OR: 2.34; p < .01). In patients with possible respiratory acute affections we found a higher neutrophil, higher monocyte, a higher NLR and a more elevation in d‐dimer. In the Sepsis group showed higher level of white blood cell, C‐reactive protein, d‐dimer, and procalcitonin.

Conclusions

Our study confirms that patients with COVID‐19 have typical radiological and laboratory characteristics. The parameters highlighted in the study can help identify COVID‐19 patients, also highlighting which are the main differential diagnoses to be made and the parameters that facilitate the differential diagnosis.
Corporate judicial dissolution in China
Authors: Lin Shaowei
Published: May 2021

Corporate judicial dissolution was formally introduced into Chinese Company Law in 2005, and yet there has been scant academic research exploring the function and implications of this procedure. This paper aims to rectify this by offering a comprehensive empirical study of the practice. Research shows that the procedure has been increasingly exercised by shareholders, though the total number of such cases is relatively small. The research also revealed many flaws in the procedure, which is not surprising; teething troubles are all but inevitable for a new procedure. The study also reveals that the courts do not strictly follow the relevant provisions of the Company Law and Judicial Interpretations when adjudicating judicial dissolution cases. Instead, Chinese judges appear to have created their own specific rules, a practice that runs counter to China's current legal system. Finally, this article proposes that the shareholder oppression could be introduced and enacted as one of the grounds to initiate the judicial dissolution.
Granulomatous prostatitis with high suspicion of prostatic adenocarcinoma on radiological imaging
Authors: Ambe Yoshiki , Nakamura Masaki , Shirakawa Norihide , Inatsu Hiroki , Amakawa Ryo , Inoue Yasushi , Yoshimatsu Tadashi , Miura Sakiko , Morikawa Teppei , Kusakabe Masashi , Shiga Yoshiyuki
Published: May 2021

Introduction

Granulomatous prostatitis is a benign inflammatory condition of the prostate that may mimic prostatic adenocarcinoma on magnetic resonance imaging findings. Even in the era of multiparametric magnetic resonance imaging, the differential diagnosis of granulomatous prostatitis from malignancy remains difficult.

Case presentation

A 69‐year‐old man with abnormal magnetic resonance imaging and positron emission tomography/magnetic resonance imaging findings, and a prostate‐specific antigen value of 2.48 ng/mL underwent prostate needle biopsy. He had a history of urinary tract infection 3 months prior to presentation. Multiparametric magnetic resonance imaging showed low‐intensity signals on T2‐weighted images, slightly high‐intensity signals on diffusion‐weighted images, and low values on apparent diffusion coefficients. The prostate imaging‐reporting and data system version 2 score was 3. Histological examination revealed granulomatous prostatitis.

Conclusion

For patients with preceding urinary tract infections, granulomatous prostatitis should be considered as a differential diagnosis, even when magnetic resonance imaging and positron emission tomography suggest prostatic adenocarcinoma.
The effect of nanoparticles of cobalt–chromium on human aortic endothelial cells in vitro
Authors: Zhu Wenxiu , Zhang Rui , Liu Song , Tian Jiawei , Lv Xiaobing , Yu Fei , Xin Hui
Published: May 2021

Despite advances in stent technology for vascular interventions, in‐stent restenosis (ISR) remains a main complication. The corrosion of cobalt–chromium (CoCr) alloy coronary stents has been identified to be associated with ISR, whereas its role in ISR has not been elucidated. In the current work, CoCr nanoparticles, simulated corrosion products of CoCr alloy, were used to investigate their effect on the endothelial cells. It has been demonstrated that the cell viability declines and the cell membrane is damaged, indicating the cytotoxicity of CoCr nanoparticles. The expression of GRP78, CHOP, and cleaved‐caspase12 proteins has increased when exposed to CoCr nanoparticles, suggesting that CoCr nanoparticles induced cell apoptosis through endoplasmic reticulum (ER) stress‐mediated apoptotic pathway. An increased release of adhesion and inflammatory mediators was also induced by CoCr nanoparticles, including ICAM‐1, VCAM‐1, IL‐1β, IL‐6, and TNF‐α. Our results demonstrated that CoCr nanoparticles could trigger apoptosis, adhesion, and inflammation. These findings indicated potential damaging effects of CoCr nanoparticles on the vascular endothelium, which suggested corrosion of CoCr alloy may promote the progression and development of ISR.
Lrp5 Mutant and Crispant Zebrafish Faithfully Model Human Osteoporosis, Establishing the Zebrafish as a Platform for CRISPR-Based Functional Screening of Osteoporosis Candidate Genes
Authors: Bek Jan Willem , Shochat Chen , De Clercq Adelbert , De Saffel Hanna , Boel Annekatrien , Metz Juriaan , Rodenburg Frans , Karasik David , Willaert Andy , Coucke Paul J
Published: May 2021

Genomewide association studies (GWAS) have improved our understanding of the genetic architecture of common complex diseases such as osteoporosis. Nevertheless, to attribute functional skeletal contributions of candidate genes to osteoporosis-related traits, there is a need for efficient and cost-effective in vivo functional testing. This can be achieved through CRISPR-based reverse genetic screens, where phenotyping is traditionally performed in stable germline knockout (KO) mutants. Recently it was shown that first-generation (F0) mosaic mutant zebrafish (so-called crispants) recapitulate the phenotype of germline KOs. To demonstrate feasibility of functional validation of osteoporosis candidate genes through crispant screening, we compared a crispant to a stable KO zebrafish model for the lrp5 gene. In humans, recessive loss-of-function mutations in LRP5, a co-receptor in the Wnt signaling pathway, cause osteoporosis-pseudoglioma syndrome. In addition, several GWAS studies identified LRP5 as a major risk locus for osteoporosis-related phenotypes. In this study, we showed that early stage lrp5 KO larvae display decreased notochord mineralization and malformations of the head cartilage. Quantitative micro-computed tomography (micro-CT) scanning and mass-spectrometry element analysis of the adult skeleton revealed decreased vertebral bone volume and bone mineralization, hallmark features of osteoporosis. Furthermore, regenerating fin tissue displayed reduced Wnt signaling activity in lrp5 KO adults. We next compared lrp5 mutants with crispants. Next-generation sequencing analysis of adult crispant tissue revealed a mean out-of-frame mutation rate of 76%, resulting in strongly reduced levels of Lrp5 protein. These crispants generally showed a milder but nonetheless highly comparable skeletal phenotype and a similarly reduced Wnt pathway response compared with lrp5 KO mutants. In conclusion, we show through faithful modeling of LRP5-related primary osteoporosis that crispant screening in zebrafish is a promising approach for rapid functional screening of osteoporosis candidate genes. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
A N-Terminus Domain Determines Amelogenin's Stability to Guide the Development of Mouse Enamel Matrix
Authors: Huang Yulei , Bai Yushi , Chang Chih , Bacino Margot , Cheng Ieong Cheng , Li Li , Habelitz Stefan , Li Wu , Zhang Yan
Published: May 2021

Amelogenins, the principal proteins in the developing enamel microenvironment, self-assemble into supramolecular structures to govern the remodeling of a proteinaceous organic matrix into longitudinally ordered hydroxyapatite nanocrystal arrays. Extensive in vitro studies using purified native or recombinant proteins have revealed the potential of N-terminal amelogenin on protein self-assembly and its ability to guide the mineral deposition. We have previously identified a 14-aa domain (P2) of N-terminal amelogenin that can self-assemble into amyloid-like fibrils in vitro. Here, we investigated how this domain affects the ability of amelogenin self-assembling and stability of enamel matrix protein scaffolding in an in vivo animal model. Mice harboring mutant amelogenin lacking P2 domain had a hypoplastic, hypomineralized, and aprismatic enamel. In vitro, the mutant recombinant amelogenin without P2 had a reduced tendency to self-assemble and was prone to accelerated hydrolysis by MMP20, the prevailing metalloproteinase in early developing enamel matrix. A reduced amount of amelogenins and a lack of elongated fibrous assemblies in the development enamel matrix of mutant mice were evident compared with that in the wild-type mouse enamel matrix. Our study is the first to demonstrate that a subdomain (P2) at the N-terminus of amelogenin controls amelogenin's assembly into a transient protein scaffold that resists rapid proteolysis during enamel development in an animal model. Understanding the building blocks of fibrous scaffold that guides the longitudinal growth of hydroxyapatites in enamel matrix sheds light on protein-mediated enamel bioengineering. © 2021 American Society for Bone and Mineral Research (ASBMR).
Non‐invasive urine markers for the differentiation between RCCs and oncocytoma
Authors: von Brandenstein Melanie , Herden Jan , Köditz Barbara , Huerta Manuel , Nestler Tim , Heidenreich Axel , Fries Jochen W.U.
Published: May 2021

Background

Recently, our group showed that Vim3 is overexpressed in tissue samples of renal oncocytomas and Mxi‐2 in clear cell renal carcinoma (ccRCC). The mechanism leading to the truncation of both proteins is known and involves with two miRs, both detectable in urine. Since the analysis of miRs is time‐consuming, our aim was to identify the truncated proteins in urine instead. Furthermore, urine samples from small renal masses (SRMs) (n = 45, <4 cm) were analyzed to get a pre‐surgical differentiation of the cancer subtypes.

Methods

Urines were accessed from the urological biobank (n = 350). Proteins were isolated from urine samples, and Western blots were performed. Each sample was analyzed with ELISA for the expression of Vim3 and Mxi‐2. A lateral flow assay was established. For the detection of SRMs, the miRs were isolated and qRT‐PCR was performed.

Results

A significant increase of Vim3 in urines from patients with oncocytoma (n = 20) was detectable with ELISA compared to all other subtypes of RCCs (chromophobe (n = 50), papillary (n = 40), ccRCC (n = 200), and controls (n = 40) (***p < 0.0001)). Mxi‐2 was predominantly overexpressed in ccRCCs (***p < 0.0001). Lateral flow assay of Vim3 and Mxi‐2 shows two bands in the case of oncocytoma and ccRCC indicating the specificity of this test.

For SRMs, an overexpression of miR‐15a/Mxi2 was detectable in urine samples from ccRCC and chromoRCC patients. In contrast to that, miR‐498/Vim3 were predominantly overexpressed in oncocytoma patients.

Conclusion

Both proteins (Vim3 and Mxi‐2) were detectable in patients’ urines and can be used for the non‐invasive differentiation of kidney cancers.
Matching, induction, and covariance with mixed response‐contingent food and noncontingent food
Authors: Baum William M.
Published: May 2021

The multiscale molar view of behavior is based on three basic laws of behavior: the Law of Allocation, the Law of Induction, and the Law of Covariance. Experiments that mix response‐contingent food with noncontingent food shed light on these three laws. Food, like other phylogenetically important events, induces various activities that compete in allocation. Quantitative accounts represent induction with power functions. These power functions define activities' competitive weights, and relative time allocation among activities matches relative competitive weight. Behavior–food covariance determines which activities are induced. Phylogenetic (behavior–fitness) covariance determines which adjunctive activities are induced. Ontogenetic covariance may be represented in feedback functions. Feedback functions for variable‐interval schedules may be observed even when overlaid by noncontingent food deliveries. Equations derived from the three laws describe responding in experiments with mixed response‐contingent and noncontingent food. Equations derived here accounted for responding in three data sets: (a) from Rachlin and Baum (1972); (b) a new data set in which overall food rate was fixed while the proportion of response‐contingent and noncontingent food varied; and (c) a new data set in which food occurred according to various variable‐interval schedules. The same pigeons served throughout. All results were accommodated by the derived equations.
Usefulness of the l‐type Wako Helicobacter pylori antibody J test
Authors: Tokai Yoshitaka , Fujisaki Junko , Ishizuka Naoki , Osumi Hiroki , Namikawa Ken , Yoshimizu Shoichi , Horiuchi Yusuke , Ishiyama Akiyoshi , Yoshio Toshiyuki , Hirasawa Toshiaki , Miki Kazumasa , Tsuchida Tomohiro
Published: May 2021

Background and Aim

Helicobacter pylori antibody levels in the blood are currently measured using an ELISA. In April 2016, FUJIFILM Wako Pure Chemical Corporation launched the “l‐type Wako Helicobacter pylori antibody J" test, which is based on the latex agglutination turbidimetric immunoassay. In this study, we investigated the usefulness of the Wako test.

Methods

We measured H. pylori antibody levels using both the ELISA and Wako test in 180 patients who underwent upper gastrointestinal endoscopy at our hospital between September 2017 and February 2019. Ninety patients were infected with H. pylori. We calculated the diagnostic accuracy, sensitivity, and specificity of each test and the concordance rate between the ELISA and Wako test. If lower limits of 90% confidence intervals (CIs) for each diagnostic validity exceeded the 85% threshold, the usefulness of the diagnostic test was confirmed.

Results

The diagnostic accuracy, sensitivity, and specificity were 94.4% (90% CI, 90.8–97.0%), 94.4% (90% CI, 88.7–97.8%), and 94.4% (90% CI, 88.7–97.8%), respectively, when the Wako test was used, and 94.4% (90% CI, 90.8–97.0%), 88.9% (90% CI, 81.9–93.8%), and 100% (90% CI, 96.0–100%), respectively, when the ELISA was used. The concordance rate between the two tests was high (κ = 0.8444).

Conclusions

We confirmed the usefulness of the Wako test, especially when screening for H. pylori infection, due to its high sensitivity.
Rural employment guarantee programme in India and its impact on household educational decisions: A focus on private coaching
Authors: Das Upasak
Published: May 2021

This paper evaluates the impact of household participation in a large‐scale public works programme in India on educational decisions including children schooling and expenditure incurred on private coaching and other educational components. Exogenous variation in proximity of households to a river is used to control for the potential endogeneity. The findings indicate positive impact of the programme on expenditure on private coaching while having no impact on other educational expenditures indicating higher income elasticity of private coaching. The paper thus emphasizes on various direct and indirect benefits of the programme which necessitate its effective implementation at the local level.
Regional Gas Exchange Measured by 129Xe Magnetic Resonance Imaging Before and After Combination Bronchodilators Treatment in Chronic Obstructive Pulmonary Disease
Authors: Mummy David G. , Coleman Erika M. , Wang Ziyi , Bier Elianna A. , Lu Junlan , Driehuys Bastiaan , Huang Yuh‐Chin
Published: May 2021

Background

Hyperpolarized 129Xe magnetic resonance imaging (MRI) provides a non‐invasive assessment of regional pulmonary gas exchange function. This technique has demonstrated that chronic obstructive pulmonary disease (COPD) patients exhibit ventilation defects, reduced interstitial barrier tissue uptake, and poor transfer to capillary red blood cells (RBCs). However, the behavior of these measurements following therapeutic intervention is unknown.

Purpose

To characterize changes in 129Xe gas transfer function following administration of an inhaled long‐acting beta‐agonist/long‐acting muscarinic receptor antagonist (LABA/LAMA) bronchodilator.

Study Type

Prospective.

Population

Seventeen COPD subjects (GOLD II/III classification per Global Initiative for Chronic Obstructive Lung Disease criteria) were imaged before and after 2 weeks of LABA/LAMA therapy.

Field Strength/Sequences

Dedicated ventilation imaging used a multi‐slice 2D gradient echo sequence. Three‐dimensional images of ventilation, barrier uptake, and RBC transfer used an interleaved, radial, 1‐point Dixon sequence. Imaging was acquired at 3 T.

Assessment

129Xe measurements were quantified before and after LABA/LAMA treatment by ventilation defect + low percent (vendef + low) and by barrier uptake and RBC transfer relative to a healthy reference population (bar%ref and RBC%ref). Pulmonary function tests, including diffusing capacity of the lung for carbon monoxide (DLCO), were also performed before and after treatment.

Statistical Tests

Paired t‐test, Pearson correlation coefficient (r).

Results

Baseline vendef + low was 57.8 ± 8.4%, bar%ref was 73.2 ± 19.6%, and RBC%ref was 36.5 ± 13.6%. Following treatment, vendef + low decreased to 52.5 ± 10.6% (P < 0.05), and improved in 14/17 (82.4%) of subjects. However, RBC%ref decreased in 10/17 (58.8%) of subjects. Baseline measurements of bar%ref and DLCO were correlated with the degree of post‐treatment change in vendef + low (r = −0.49, P < 0.05 and r = −0.52, P < 0.05, respectively).

Conclusion

LABA/LAMA therapy tended to preferentially improve ventilation in subjects whose 129Xe barrier uptake and DLCO were relatively preserved. However, newly ventilated regions often revealed RBC transfer defects, an aspect of lung function opaque to spirometry. These microvasculature abnormalities must be accounted for when assessing the effects of LABA/LAMA therapy.

Level of Evidence

1

Technical Efficacy Stage

4
Selecting Markov chain orders for generating daily precipitation series across different Köppen climate regimes
Authors: Wilson Kemsley Sarah , Osborn Timothy J. , Dorling Stephen R. , Wallace Craig , Parker Joanne
Published: May 2021

Markov chain models are a commonly used statistical technique to generate realistic sequences of precipitation, but the choice of model order can strongly affect their performance. Although it is widely accepted that a first‐order Markov chain reproduces precipitation occurrence in temperate latitudes quite well, it is also well known that first‐order models have several shortcomings. These include a limited memory of rare events and inaccurately reproducing the distribution of dry‐spell lengths, and their performance outside of temperate regions is less well understood. We present, therefore, the first assessment of model‐order optimization which is both global in extent and which uses four evaluation methods: the Bayesian information criterion (BIC) and each model‐order's ability to reproduce wet‐ and dry‐spell lengths, and the interannual variability of precipitation occurrence. As well as a global analysis, we also assessed Markov chain performance and model‐order selection separately within five climate regimes based on the Köppen classification system: tropical, dry, temperate, continental and polar. These metrics were used to determine the best performing model‐order to generate realistic time series of precipitation across the five different climate regimes. We find that the choice of model order is most sensitive to the performance metric and less dependent on the climate regime. Across all regimes, we show that a first‐order model performs best when evaluated with BIC and for generating realistic wet‐spell distributions across all climate regimes except tropical, where third order performs best. We also find that a third‐order model reproduces observed dry‐spell distributions the best and second order commonly reproduces the interannual variability of precipitation occurrence across all regimes except tropical, where third order once again performs best. Our findings highlight the benefits of a flexible and tailored approach to the choice of Markov chain order for constructing precipitation series.
Directional Raman scattering spectra of metal–sulfur bonds at smooth gold and silver substrates
Authors: Nyamekye Charles K. A. , Weibel Stephen C. , Smith Emily A.
Published: May 2021

The gold–sulfur (Au–S) and silver–sulfur (Ag–S) bonds are integral to the surface modification of metal films with alkanethiol monolayers. Although the metal–sulfur bond can be characterized with surface‐enhanced Raman spectroscopy (SERS) at roughened metal films, some applications require or perform better when using a smooth metal surface, which is not suitable for SERS signal enhancement. Directional‐surface‐plasmon‐coupled Raman scattering (directional Raman scattering) is an approach to measure metal–sulfur bonds on smooth metal films with sub‐monolayer sensitivity. The metal–sulfur bonds formed from a benzenethiol monolayer on smooth planar gold or silver films are observed in the directional Raman scattering spectra between 240 and 270 cm−1; the signal‐to‐noise ratio of the Au–S Raman peak is 60. Importantly, the directional Raman scattering signal measured with smooth metal surfaces can be simply modeled and easily compared across many samples. Directional Raman scattering can also be measured at roughened metal films, which makes it applicable for many analyses.
Profiles of Maltreatment in the Child Welfare System: Predicting Mental Health Outcomes and Examining Age as a Moderator
Authors: Huguenel Brynn M. , Leon Scott C. , Hindt Lauren A. , Lutz Nathan , Osborne Jennifer
Published: May 2021

This longitudinal study explored the unique profiles of maltreatment among youth in the child welfare system and examined their relation to mental health outcomes over time. We additionally examined the moderating role of age. Participants included 316 youth in the foster care system (age range: 6–13 years). Data were collected through the Department of Children and Family Services upon youths’ entry into foster care, then quarterly for the duration of care. A latent profile analysis identified five profiles of maltreatment, categorized as primary neglect (PN), neglect and physical abuse (PA), complex trauma, complex trauma with severe sexual abuse (SA), and neglect with SA. A hierarchical general linear model applied to the data revealed that all four classes predicted higher internalizing symptom trajectories compared with the PN reference class, event rate ratios (eRRs) = 1.19–1.37, but none of these associations were significantly moderated by age. Membership in the two classes categorized by complex trauma predicted higher externalizing behavior trajectories as compared to the PN reference class, eRRs = 1.11–1.13. The relation between membership in the neglect with SA class and externalizing behaviors was moderated by age, eRR = 0.83. Finally, membership in all four classes predicted higher posttraumatic stress symptoms as compared with the reference group, eRRs = 1.84–2.45, and with all associations moderated by age, eRRs = 0.51–0.53. These findings provide insight into the maltreatment experiences of youth in the child welfare system and have important implications for treatment needs.
Prognostic Role of Tumor‐Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma
Authors: Hori Yukiko , Kubota Akira , Yokose Tomoyuki , Furukawa Madoka , Matsushita Takeshi , Katsumata Noriyuki , Oridate Nobuhiko
Published: May 2021

Objectives/Hypothesis

Occult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor‐infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate‐ or high‐grade budding scores was investigated as a prognostic marker for occult neck metastases.

Study Design

Retrospective study.

Methods

Specimens from 62 patients with early oral tongue SCC treated with only primary surgery were analyzed by immunohistochemistry for CD4+, CD8+, FoxP3+, and CD45RO+ T cells and CD163+ macrophages. The highest number of each TIL subtype was counted in two areas of parenchyma and stroma in the tumor (Tumor) and peripheral stroma of the invasion margin.

Results

Based on multivariate analysis, a high density of Tumor CD163+ macrophages served as the poorest prognostic factor for regional control (RC) and disease‐free survival (DFS). Patients with both a high density of Tumor CD163+ macrophages and an intermediate‐ or a high‐grade budding score had a poor prognosis for RC according to the log‐rank test.

Conclusions

In summary, each TIL subtype may use different mechanisms during early and advanced stages of oral tongue SCC. A high density of Tumor CD163+ macrophages was determined to be a risk factor for RC and DFS as well as an additional stratification factor for RC in patients with intermediate‐ or high‐grade budding scores. Therefore, identifying TIL subtypes in daily clinical practice can help determine a more successful and individualized therapeutic approach for early oral tongue SCC.

Level of Evidence

Step 4 (Level 4) Laryngoscope, 131:2512–2518, 2021
Discordant SARS‐CoV‐2 Detection in the Nasopharynx Versus Trachea for Patients With Tracheostomies
Authors: Smith Joshua D. , Correll Jason A. , Stein Jennifer L. , Kupfer Robbi A. , Hogikyan Norman D. , Morrison Robert J. , Stein Andrew P.
Published: May 2021

Objectives/Hypothesis

Patients with tracheostomies have an anatomically altered connection between their upper and lower airways that could impact SARS‐CoV‐2 testing. Our goal was to evaluate for discordance in SARS‐CoV‐2 detection in hospitalized patients with COVID‐19 and tracheostomies based on the site analyzed.

Study Design

Retrospective chart review.

Methods

This single‐institution study evaluated hospitalized patients with COVID‐19 who had tracheostomies placed during their treatment. We analyzed SARS‐CoV‐2 RNA nucleic acid amplification test (NAAT) results after tracheostomy. All included patients had nasopharyngeal (NP) and tracheal (TR) samples taken within a 48‐hour period, allowing us to characterize rate of test concordance.

Results

Forty‐five patients met our inclusion criteria. Thirty‐two (71.1%) patients had entirely concordant results after tracheostomy. However, 13 (28.9%) patients had at least one set of discordant results, the majority of which were NP negative and TR positive. There were no statistically significant differences in demographic or clinical variables, including time to tracheostomy and time to testing, among patients with concordant versus discordant SARS‐CoV‐2 results.

Conclusion

This represents the first study to examine SARS‐CoV‐2 RNA NAAT concordance between NP and TR sites in hospitalized patients with COVID‐19 and tracheostomies. One‐third of patients demonstrated discordant testing when NP and TR specimens were collected within a 48‐hour time period. Thus, patients with tracheostomies may have a higher false‐negative rate if only one site is assessed for SARS‐CoV‐2. We recommend analyzing samples from both the nasopharynx and trachea for these patients until more prospective data exist.

Level of Evidence

4 Laryngoscope, 131:E2634–E2638, 2021
Narrative review of the role of inflammation in gastroesophageal reflux disease. Can food allergies play a part?
Authors: Swain Lucy Kensett
Published: May 2021

Acid suppression is the accepted treatment for gastroesophageal reflux disease, despite being ineffective in one third of patients. Certain conditions presenting as reflux may later be attributed to food allergy (infant cow's milk allergy; eosinophilic esophagitis), but the role of food allergy in adult reflux disease has rarely been investigated. The mechanisms of gastroesophageal reflux disease are examined to explore potential subgroups within the population, such as undisclosed food allergy, which may determine the responsiveness to treatment. The relevant literature was searched systematically using ProQuest Dialog, yielding 113 papers that were evaluated for quality. The extracted evidence was formed into a mechanistic diagram representing the processes of disease. As yet, insufficient research exists to evaluate the relationship between food allergies and reflux in adults. Of significance, however, is the potential for multiple variables to affect the integrity of the esophageal mucosa, thereby allowing symptoms to emerge which are independent of acid exposure. Where nonacidic drivers of inflammation exist, acid suppression is unlikely to offer adequate symptom resolution and may serve to explain the high proportion of nonresponders in this group. The review concludes that symptoms of gastroesophageal reflux may emerge in response to the coexistence of physiological reflux and esophageal mucosal inflammation. The latter may arise due to reflux‐induced acid erosion, or due to alternative endogenous sources of inflammation. When a patient presents with refractory reflux and a history of allergic disease, the role of antigen‐induced inflammation should be considered for further investigation. Nonallergic individuals presenting with refractory reflux symptoms may benefit from further analysis of relevant co‐morbidities that have the capacity to compromise mucosal integrity, including obesity or psychological stress. The identification of specific mediators of inflammation in refractory reflux disease may enable the development of personalized treatment regimes which improve outcomes and reduce the reliance on acid suppressants.