bluuebunny/crossref_metadata_2025 huggingface dataset:
A Computer‐Driven Scaffold‐Hopping Approach Generating New PTP1B Inhibitors from the Pyrrolo[1,2‐a]quinoxaline Core
Authors: García‐Marín Javier , Griera Mercedes , Alajarín Ramón , Rodríguez‐Puyol Manuel , Rodríguez‐Puyol Diego , Vaquero Juan J.
Published: June 2021

Protein tyrosine phosphatase 1B (PTP1B) is a very promising target for the treatment of metabolic disorders such as type II diabetes mellitus. Although it was validated as a promising target for this disease more than 30 years ago, as yet there is no drug in advanced clinical trials, and its biochemical mechanism and functions are still being studied. In the present study, based on our experience generating PTP1B inhibitors, we have developed and implemented a scaffold‐hopping approach to vary the pyrrole ring of the pyrrolo[1,2‐a]quinoxaline core, supported by extensive computational techniques aimed to explain the molecular interaction with PTP1B. Using a combination of docking, molecular dynamics and end‐point free‐energy calculations, we have rationally designed a hypothesis for new PTP1B inhibitors, supporting their recognition mechanism at a molecular level. After the design phase, we were able to easily synthesize proposed candidates and their evaluation against PTP1B was found to be in good concordance with our predictions. Moreover, the best candidates exhibited glucose uptake increments in cellulo model, thus confirming their utility for PTP1B inhibition and validating this approach for inhibitors design and molecules thus obtained.
Disparities in magnetic resonance imaging of the prostate for traditionally underserved patients with prostate cancer
Authors: Quinn Timothy P. , Sanda Martin G. , Howard David H. , Patil Dattatraya , Filson Christopher P.
Published: June 2021

BACKGROUND

Prebiopsy magnetic resonance imaging (MRI) of the prostate improves detection of significant tumors, while decreasing detection of less‐aggressive tumors. Therefore, its use has been increasing over time. In this study, the use of prebiopsy MRI among Medicare beneficiaries with prostate cancer was examined. It was hypothesized that patients of color and those in isolated areas would be less likely to undergo this approach for cancer detection.

METHODS

Using cancer registry data from the Surveillance, Epidemiology, and End Results (SEER) program linked to billing claims for fee‐for‐service Medicare beneficiaries, men with nonmetastatic prostate cancer were identified from 2010 through 2015 with prostate‐specific antigen (PSA) <30 ng/mL. Outcome was prebiopsy MRI of the prostate performed within 6 months before diagnosis (ie, Current Procedural Terminology 72197). Exposures were patient race/ethnicity and rural/urban status. Multivariable regression estimated the odds of prebiopsy prostate MRI. Post hoc analyses examined associations with the registry‐level proportion of non‐Hispanic Black patients and MRI use, as well as disparities in MRI use in registries with data on more frequent use of prostate MRI.

RESULTS

There were 50,719 men identified with prostate cancer (mean age, 72.1 years). Overall, 964 men (1.9% of cohort) had a prebiopsy MRI. Eighty percent of patients with prebiopsy MRI lived in California, New Jersey, or Connecticut. Non‐Hispanic Black men (0.6% vs 2.1% non‐Hispanic White; odds ratio [OR], 0.28; 95% CI, 0.19‐0.40) and men in less urban areas (1.1% vs 2.2% large metro; OR, 0.65; 95% CI, 0.44‐0.97) were less likely to have prebiopsy MRI of the prostate.

CONCLUSIONS

Non‐Hispanic Black patients with prostate cancer and those in less urban areas were less likely to have prebiopsy MRI of the prostate during its initial adoption as a tool for improving prostate cancer detection.
Subclassification of the Bethesda Category III (AUS/FLUS): A study of thyroid FNA cytology based on ThinPrep slides from the National Cancer Center in China
Authors: Zhao Huan , Guo HuiQin , Zhao LinLin , Cao Jian , Sun Yue , Wang Cong , Zhang ZhiHui
Published: June 2021

Background

The atypia of an undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a heterogeneous category, which includes various cell patterns. The subclassification of AUS/FLUS was suggested in the 2017 TBSRTC. However, the risk of malignancy (ROM) associated with different subgroups remains unresolved. Herein, AUS/FLUS aspirates were subclassified, from which the ROM of each subgroup was determined.

Methods

All cases undergoing fine‐needle aspiration (FNA) from July 2013 to December 2018 were reviewed. Of 12,913 thyroid FNAs, 1053 (8.2%) were AUS/FLUS. The slides of 222 patients with AUS/FLUS with surgical follow‐up were reviewed and subclassified according to the recommendations of the 2017 TBSRTC. There were 195 aspirates consistently diagnosed as AUS/FLUS and subclassified as cytologic atypia 1 (AUS‐C1); cytologic atypia 2 (AUS‐C2); architectural atypia (AUS‐A); cytologic and architectural atypia (AUS‐C&A); Hürthle cell aspirates (AUS‐H); atypia, not otherwise specified (AUS‐NOS); and atypical lymphoid cells, rule out lymphoma (AUS‐L).

Results

Malignancy was identified in 83.3% (185 of 222) of the AUS/FLUS nodules. The AUS‐C1 group was the most common (62.1%), followed by the AUS‐C&A (12.8%), AUS‐C2 (10.8%), AUS‐H (6.7%), AUS‐NOS (5.6%), AUS‐L (1.5%), and AUS‐A (0.5%) groups. AUS‐C1 had the highest ROM (92.6%) among the groups and varied significantly from that of the AUS‐C&A (P = .171), AUS‐C2 (P = .001), AUS‐H (P = .001), and AUS‐NOS (P < .001) groups.

Conclusions

As a heterogeneous category of TBSRTC, the ROM for AUS/FLUS varies greatly among medical centers. Subclassification of AUS/FLUS might be helpful in identifying nodules with a high ROM in this category and improving the management of such nodules.
The cost, survival, and quality‐of‐life implications of guideline‐discordant imaging for prostate cancer
Authors: Winn Aaron N. , Kelly Matthew , Ciprut Shannon , Walter Dawn , Gold Heather T. , Zeliadt Steven B. , Sherman Scott E. , Makarov Danil V.
Published: June 2021

Background

National Comprehensive Cancer Network (NCCN) guidelines for incident prostate cancer staging imaging have been widely circulated and accepted as best practice since 1996. Despite these clear guidelines, wasteful and potentially harmful inappropriate imaging of men with prostate cancer remains prevalent.

Aim

To understand changing population‐level patterns of imaging among men with incident prostate cancer, we created a state‐transition microsimulation model based on existing literature and incident prostate cancer cases.

Methods

To create a cohort of patients, we identified incident prostate cancer cases from 2004 to 2009 that were diagnosed in men ages 65 and older from SEER. A microsimulation model allowed us to explore how this cohort's survival, quality of life, and Medicare costs would be impacted by making imaging consistent with guidelines. We conducted a probabilistic analysis as well as one‐way sensitivity analysis.

Results

When only imaging high‐risk men compared to the status quo, we found that the population rate of imaging dropped from 53 to 38% and average per‐person spending on imaging dropped from $236 to $157. The discounted and undiscounted incremental cost‐effectiveness ratios indicated that ideal upfront imaging reduced costs and slightly improved health outcomes compared with current practice patterns, that is, guideline‐concordant imaging was less costly and slightly more effective.

Conclusion

This study demonstrates the potential reduction in cost through the correction of inappropriate imaging practices. These findings highlight an opportunity within the healthcare system to reduce unnecessary costs and overtreatment through guideline adherence.
Probability and topic‐based data transmission protocol
Authors: Saito Takumi , Nakamura Shigenari , Enokido Tomoya , Takizawa Makoto
Published: June 2021

In the fog computing (FC) models, a fog node supports not only routing functions but also application processes. By the application processes, output data are calculated on input data from sensors and other nodes and sent to target fog nodes which can calculate on the output data. In this article, we consider the mobile topic‐based publish/subscribe fog computing (MPSFC) model where mobile fog nodes communicate with one another by publishing and subscribing messages in wireless networks. Subscription topics of a fog node denote input data on which the node can calculate output data. Publication topics of a message show data carried by the message. In the topic‐based data transmission (TBDT) protocol proposed in our previous studies, while a fewer number of messages are transmitted, the delivery ratio of messages is smaller than the epidemic routing protocol. In this article, we newly propose a pair of time‐to‐live‐based data transmission (TTLBDT) and probability and topic‐based data transmission (PTBDT) protocols in order to increase the delivery ratio. If another node is found in the communication range, a fog node forwards messages to the node. Even if the node is not a target node, the node receives the message with some probability in the PTBDT protocol. In the evaluation, we show the delivery ratios in the TTLBDT and PTBDT protocols are larger than the TBDT protocol. In addition, we show the number of messages exchanged in the PTBDT protocol is smaller than the epidemic routing protocol.
Curation Guidelines for de novo Generated Transposable Element Families
Authors: Storer Jessica M. , Hubley Robert , Rosen Jeb , Smit Arian F. A.
Published: June 2021

Transposable elements (TEs) have the ability to alter individual genomic landscapes and shape the course of evolution for species in which they reside. Such profound changes can be understood by studying the biology of the organism and the interplay of the TEs it hosts. Characterizing and curating TEs across a wide range of species is a fundamental first step in this endeavor. This protocol employs techniques honed while developing TE libraries for a wide range of organisms and specifically addresses: (1) the extension of truncated de novo results into full‐length TE families; (2) the iterative refinement of TE multiple sequence alignments; and (3) the use of alignment visualization to assess model completeness and subfamily structure. © 2021 Wiley Periodicals LLC.

Basic Protocol: Extension and edge polishing of consensi and seed alignments derived from de novo repeat finders

Support Protocol: Generating seed alignments using a library of consensi and a genome assembly
Temporomandibular disorders in an adult population in northern Norway: A cross‐sectional study
Authors: Hadler‐Olsen Elin , Thon Elizabeth , Holde Gro Eirin , Jönsson Birgitta , Oscarson Nils , Tillberg Anders
Published: June 2021

Objectives

The aim of the study was to assess the prevalence of symptoms indicative of temporomandibular disorders (TMD) in an adult population in Troms County in Northern Norway, as well as the associations between TMD and socio‐demographic factors, dental status, self‐reported general, and oral health as well as oral health related quality of life (OHQoL).

Methods

Data were collected from a structured questionnaire and a clinical examination of a random sample of almost 2000 adults, 20–79‐year‐old, in Troms County in Northern Norway.

Results

Women had a higher prevalence of all self‐reported and clinical signs of pain and dysfunction in the temporomandibular complex compared to men. For both genders, sounds from the temporomandibular joint (TMJ) upon clinical examination was the most common symptom, followed by pain to palpation of jaw muscles. Headache was the most common of the self‐reported symptoms and sounds from the TMJ the second most common. Young women had a higher prevalence of self‐reported headache and jaw‐ and face pain compared to middle‐aged and elderly women. TMD‐related symptoms of pain were significantly associated with poor self‐reported general health and correlated with OHQoL as assessed by the oral health impact profile 14 questionnaire.

Conclusion

Being women and having moderate to poor self‐reported general health were associated with clinical signs and self‐reported symptoms of pain in the jaw, face and head region. Self‐reported symptoms of TMD correlated more strongly with OHQoL than clinical signs.
Biotechnology of Plastic Waste Degradation, Recycling, and Valorization: Current Advances and Future Perspectives
Authors: Qin Zi‐Hao , Mou Jin‐Hua , Chao Christopher Yu Huang , Chopra Shauhrat Singh , Daoud Walid , Leu Shao‐yuan , Ning Zhi , Tso Chi Yan , Chan Chak Keung , Tang Shixing , Hathi Zubeen Jyotiwadan , Haque Md Ariful , Wang Xiang , Lin Carol Sze Ki
Published: June 2021

Although fossil‐based plastic products have many attractive characteristics, their production has led to severe environmental burdens that require immediate solutions. Despite these plastics being non‐natural chemical compounds, they can be degraded and metabolized by some microorganisms, which suggests the potential application of biotechnologies based on the mechanism of plastic biodegradation. In this context, microbe‐based strategies for the degradation, recycling, and valorization of plastic waste offer a feasible approach for alleviating environmental challenges created by the accumulation of plastic waste. This Minireview highlights recent advances in the biotechnology‐based biodegradation of both traditional polymers and bio‐based plastics, focusing on the mechanisms of biodegradation. From an application perspective, this Minireview also summarizes recent progress in the recycling and valorization of plastic waste, which are feasible solutions for tackling the plastic waste dilemma.
Modeling an aspirational connected network of protected areas across North America
Authors: Barnett Kevin , Belote R. Travis
Published: June 2021

Connecting protected areas remains an important global conservation strategy in the face of ongoing and future threats to biodiversity. Amid our growing understanding of how species’ distributions will respond to climate change, conservation scientists need to plan for connectivity conservation across entire continents. We modeled multiscale connectivity priorities based on the least human‐modified lands between large protected areas of North America using least‐cost and circuit theory approaches. We first identified priority corridors between large protected areas, then characterized the network’s structure to unveil priority linkages most important for maintaining network‐ and regional‐level connectivity. Agreement between least‐cost corridors and current flow varied throughout North America, reflecting permeable landscape conditions and “pinch points” where potential ecological flows may concentrate between protected areas. Priority network‐level linkages derived from each approach were similar throughout the continental network (e.g., Rocky Mountains and Canadian boreal), but critical linkages that bridged regional protected‐area networks varied. We emphasize the importance of planning for connectivity at continental scales and demonstrate the utility of multiple methods when mapping connectivity priorities across large spatial extents with wide gradients in landscape conditions.
Responses of two dominant desert plant species to the changes in groundwater depth in hinterland natural oasis, Tarim Basin
Authors: Imin Bilal , Dai Yue , Shi Qingdong , Guo Yuchuan , Li Hao , Nijat Marhaba
Published: June 2021

Groundwater is increasingly becoming a permanent and steady water source for the growth and reproduction of desert plant species due to the frequent channel cutoff events in arid inland river basins. Although it is widely acknowledged that the accessibility of groundwater has a significant impact on plant species maintaining their ecological function, little is known about the water use strategies of desert plant species to the groundwater availability in Daryaboyi Oasis, Central Tarim Basin. This study initially determined the desirable and stressing groundwater depths based on ecological and morphological parameters including UAV‐based fractional vegetation cover (FVC) images and plant growth status. Then, leaf δ13C values of small‐ and big‐sized plants were analyzed to reveal the water use strategies of two dominant woody species (Populus euphratica and Tamarix ramosissima) in response to the groundwater depth gradient. The changes in FVC and growth status of plants suggested that the actual groundwater depth should be kept at an appropriate range of about 2.1–4.3 m, and the minimum groundwater depth should be less than 7 m. This will ensure the protection of riparian woody plants at a normal growth state and guarantee the coexistence of both plant types. Under a desirable groundwater condition, water alternation (i.e., flooding and rising groundwater depth) was the main factor influencing the variation of plant water use efficiency. The obtained results indicated that big‐sized plants are more salt‐tolerant than small ones, and T. ramosissima has strong salt palatability than P. euphratica. With increasing groundwater depth, P. euphratica continuously decreases its growth status to maintain hydraulic efficiency in drought condition, while T. ramosissima mainly increases its water use efficiency first and decreases its growth status after then. Besides, in a drought condition, T. ramosissima has strong adaptability than P. euphratica. This study will be informative for ecological restoration and sustainable management of Daryaboyi Oasis and provides reference materials for future research programs.
Heterospecific competitors and seasonality can affect host physiology and behavior: key factors in disease transmission
Authors: Eleftheriou Andreas , Kuenzi Amy J. , Luis Angela D.
Published: June 2021

Ecological and environmental factors can influence the transmission of infectious diseases. They can accomplish this via effects on host susceptibility and exposure to infection, which are governed by host physiology and behavior, respectively. To better inform disease control, more information is needed about how extrinsic factors affect physiological and behavioral processes that determine transmission. We investigated how heterospecific competitors and seasonality may influence host susceptibility and intraspecific contact rates using a directly transmitted disease system, the North American deer mouse (Peromyscus maniculatus)—Sin Nombre hantavirus (SNV) system. In grasslands of western Montana, USA, deer mice compete with dominant voles (Microtus spp.) and shrews (Sorex spp.) and experience a seasonal temperate climate. Higher SNV transmission occurs primarily during spring/summer, when changes in physiology and behavior may serve as influential contributors. We hypothesized that (1) voles, and to a lesser extent shrews, will induce chronic stress, suppress immunity, and may change contact rates of deer mice; and (2) during spring/summer, deer mice may experience chronic stress, suppressed immunity, and higher contact rates, which may help explain the reported seasonality in SNV transmission. Over two years, we trapped small mammals at four grids in western Montana. Deer mice were sampled for feces and blood and evaluated for scar numbers, demography, and body condition scores (BCSs). We evaluated stress physiology with fecal corticosterone metabolites (FCMs), neutrophil/lymphocyte (N/L) ratios and BCSs, immunity with white blood cell (WBC) counts, and contact rates with scar numbers. We found that shrew density was negatively associated with stress response FCMs, suggestive of chronic stress. Additionally, although complex interactions existed, shrew and vole densities were negatively associated with BCSs, but differentially with scar numbers. N/L ratios were higher in spring/summer, whereas WBC counts were lower in summer, suggestive of chronic stress and suppressed immunity, respectively. Our results suggest that (1) heterospecific competitors may differentially influence disease transmission via stress physiology and contact rates, and that (2) chronic stress, suppressed immunity, and higher contact rates may help explain why higher SNV transmission has been previously reported during spring/summer in Montana. Our findings may extend to other directly transmitted disease systems.
Molecular mechanisms of nonself nucleic acid recognition by the innate immune system
Authors: de Oliveira Mann Carina C. , Hornung Veit
Published: June 2021

Nucleic acids (NAs) represent one of the most important classes of molecules recognized by the innate immune system. However, NAs are not limited to pathogens, but are also present within the host. As such, the immune system has evolved an elaborate set of pathogen recognition receptors (PRRs) that employ various strategies to recognize distinct types of NAs, while reliably distinguishing between self and nonself. The here‐employed strategies encompass the positioning of NA‐sensing PRRs in certain subcellular compartments that potentially come in contact with pathogens but not host NAs, the existence of counterregulatory measures that keep endogenous NAs below a certain threshold, and also the specific identification of certain nonself patterns. Here, we review recent advances in the molecular mechanisms of NA recognition by TLRs, RLRs, and the cGAS–STING axis. We highlight the differences in NA‐PRR interfaces that confer specificity and selectivity toward an NA ligand, as well as the NA‐dependent induced conformational changes required for signal transduction.
Fear not of cognition in context
Authors: Prather Richard William
Published: June 2021

How do researchers of cognitive development work to make sure that our field evolves so that our contribution to humanity is emancipatory? We can take inspiration from researchers near and far. Inspiration may be found in other areas of psychological research (social, cultural, etc.) and other social sciences (public health, sociology, etc.). Frameworks developed in other fields (e.g., intersectionality, Crenshaw, University of Chicago Legal Forum, 1989(1), 139–167) may be helpful for our own interests and questions. If so, this will require some work in determining how these tools can be used to improve the state of cognitive research.
The prenatal diagnosis of a rare circular shunt with absent pulmonary valve syndrome
Authors: Inamura Noboru , Takada Nori , Marutani Satoshi
Published: June 2021

Absent pulmonary valve syndrome (APVS) with tricuspid atresia is very rare. We report a case of APVS in which the fetus died due to severe hydrops fetalis. In addition to weakened cardiac contraction due to left ventricular noncompaction cardiomyopathy, a circular shunt through a ventricular septal defect exacerbated heart failure. Although APVS with tricuspid valve atresia is not supposed to cause a circular shunt, we herein present the echocardiographic demonstration of a case of circular shunt.
Interventions aiming to improve informed decision on prenatal screening and testing: A scoping review of the literature
Authors: Yeşilçinar İlknur , Seven Memnun , Paşalak Şeyma İnciser , Güvenç Gülten
Published: June 2021

The aim of this scoping review was to explore interventions and their effect in facilitating decision making on prenatal screening and testing among pregnant women. This review was conducted according to the Joanna Briggs Institute Methods Manual for scoping reviews. Studies published 2000–2019 that consist of interventions to facilitate pregnant women's decision making in prenatal screening and testing were specifically reviewed. A total of 27 studies are included in this scoping review. In these studies, various methods, including face‐to‐face individual or group interventions, e‐Health interventions, video‐based interventions, written educational materials, and decision aid interventions, were developed and tested for their effectiveness in facilitating informed decision making on prenatal screening and testing. While these methods appeared to be effective, further studies involving diverse populations are needed to integrate them into practice. Genetic counselors and healthcare providers working with individuals who are referred for genetic education and counseling need to work collaboratively to facilitate informed decisions on prenatal screening of women and/or their partners.
The key role of mass spectrometry in comprehensive research on new psychoactive substances
Authors: Fabregat‐Safont David , Sancho Juan V. , Hernández Félix , Ibáñez María
Published: June 2021

New psychoactive substances (NPS) are a wide group of compounds that try to mimic the effects produced by the ‘classical’ illicit drugs, including cannabis (synthetic cannabinoids), cocaine and amphetamines (synthetic cathinones) or heroin (synthetic opioids), and which health effects are still unknown for most of them. Nowadays, more than 700 compounds are being monitored by official organisms, some of which have been recently identified in seizures and/or intoxication cases. Toxicological analysis plays a pivotal role in NPS research. A comprehensive investigation on NPS, from the first identification of a novel substance until its detection in drug users to help in diagnostics and medical treatment, requires the use of a wide variety of instruments and analytical strategies. This paper illustrates the key role of mass spectrometry (MS) along a comprehensive investigation on NPS. The synthetic cannabinoid XLR‐11 and the synthetic cathinone 5‐PPDi have been chosen as representative substances of the most consumed NPS families. Moreover, both compounds have been investigated at our laboratory in different stages of the three‐step strategy considered in this article. The initial identification and characterisation of the compound in consumption products, the first reported metabolic pathway and the development of analytical methodologies for its determination (and/or their metabolites) in different toxicological samples are described. The analytical strategies and MS instruments are briefly discussed to show the reader the possibilities that MS instrumentation offer to analytical scientists. This publication aims to be a starting point for those interested on the NPS research field from an analytical chemistry point of view.
High‐resolution melting curve FRET‐PCR rapidly identifies SARS‐CoV‐2 mutations
Authors: Barua Subarna , Hoque Monirul , Kelly Patrick J. , Bai Jianfa , Hanzlicek Gregg , Noll Lance , Walz Heather , Johnson Calvin , Kyriakis Constantinos , Wang Chengming
Published: June 2021

Reverse transcription fluorescence resonance energy transfer‐polymerase chain reaction (FRET‐PCRs) were designed against the two most common mutations in severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) (A23403G in the spike protein; C14408T in the RNA‐dependent RNA polymerase). Based on high‐resolution melting curve analysis, the reverse transcription (RT) FRET‐PCRs identified the mutations in american type culture collection control viruses, and feline and human clinical samples. All major makes of PCR machines can perform melting curve analysis and thus further specifically designed FRET‐PCRs could enable active surveillance for mutations and variants in countries where genome sequencing is not readily available.
Overall uncertainty of climate change impacts on watershed hydrology in China
Authors: Zhang Shaobo , Chen Jie , Gu Lei
Published: June 2021

The hydrological projections provided by the outputs of Global Climate Models (GCMs) combining hydrological models include multi‐source uncertainties, which may challenge the formulation of relevant adaption and mitigation policies. In this paper, the overall uncertainty and the relative contribution of each uncertainty component were investigated for hydrological projections over 408 watersheds in China by using 3 shared socioeconomic pathway emission scenarios (SSP1‐2.6, SSP2‐4.5, and SSP5‐8.5), 21 GCMs, 8 bias correction methods, 4 hydrological models, and 2 sets of optimized hydrological model parameters. The results show that the total uncertainty (T) is mainly contributed by uncertainty related to global climate models (G), with the mean percentage ranging from 60.4 to 64.1%, followed by the interaction uncertainties among all components, with the mean percentage ranging from 22.0 to 26.4%. The uncertainty contribution of hydrological models (H) (6.1–9.4%) ranks third, followed by emission scenarios (S) (2.9–5.9%) and bias correction methods (B) (0.2–1.1%). The uncertainty contribution of the optimized hydrological model parameters (P) (0.2–0.3%) is almost negligible. In terms of spatial variability, the relative contribution of uncertainty related to global climate models (G) is the highest in the near future for northern China (67.5–70.6%) and in the far future for southern China (66.1–66.7%). However, it was found to be lower for the Tibetan Plateau and northwestern China (45.3–57.9%) in the near and far future. The relative contribution of hydrological model uncertainty is higher for southwestern and northwestern China and the Tibetan Plateau (7.2–19.5%) and lower for northern, eastern, and southern China (2.5–6.6%). This study highlights the importance of including multiple GCMs and hydrological models in hydrological impact studies to consider their overall uncertainty. The development of global climate models and hydrological models is still the best way to reduce the uncertainty of climate change impact studies.
When do family brand personalities lead to brand loyalty? A study of family‐owned fashion retailers in Pakistan
Authors: Sindhu Mahwish , Saleem Irfan , Arshad Muhammad
Published: June 2021

Despite the benefits that it can bring, family firms in emerging markets rarely take brand loyalty into account. Using self‐congruity theory and data from a sample of 381 customers of family‐owned fashion retailers in five major shopping malls in Lahore, this research sets out to answer the question, how do brand personalities help to generate a brand image, and ensure brand loyalty, for family firms in emerging markets? It focuses on the influence of three brand personalities—sincerity, competence, and excitement—on brand loyalty, and examines the mediating effect of brand image, and the moderating effect of brand sophistication. The results show that brand sincerity, competence, and excitement have a positive effect on brand image, which in turn positively influences brand loyalty, and that brand sincerity and brand excitement also have positive indirect effects on brand loyalty. The study highlights some avenues for future research and discusses the implications for managers working in family firms in emerging markets such as Pakistan.
Kinetic Modeling Characterization of Cellulose Modified Surface for Methylene Blue Removal from Aqueous Media
Authors: Azhar Siti Maizatul Ameera , Samsudin Ahmad Salihin , Ismail Wan Norfazilah Wan , Samah Nurlin Abu
Published: June 2021

In this work, commercial cellulose is modified with allylthiourea (Cel‐AT) to remove methylene blue (MB) from aqueous solution. Characterization study includes FTIR analysis along with UV spectrophotometer. A variety of physico‐chemical properties such as kinetic, total sorption capacity loaded and pH effect by using Cel‐AT sorbent is carried out. The main finding is the adsorption total capacity of Cel‐AT for MB is three times more than commercial cellulose (Cel) when the concentration of MB increases in batch mode. In kinetic study, the MB removal efficiency is at 90% after 5 min of removal using Cel‐AT as a sorbent and Cel‐AT fulfil pseudo second order of reaction. The optimum MB removal is at pH 11 with 95% of removal. There is spectral peak which is observed in the spectrum of FTIR and it is addressed accordingly. As a conclusion, the suggested method improves the quality of MB sorption onto the Cel‐AT in terms of contact time and less laborious.
Indian Sign Language Recognition Using Machine Learning Techniques
Authors: Sahoo Ashok Kumar
Published: June 2021

Automatic conversion of sign language to text or speech is indeed helpful for interaction between deaf or mute people with people who even do not have knowledge of sign language. This is the demand of current times to develop an automatic system to convert ISL signs to normal text and vice versa. This will be beneficial for both communities to express their fillings to one another in accessing publicly available facilities like ticketing, banking services, traffic signals, etc. A new feature extraction and selection technique using structural features and some of the best available classifiers are proposed to recognize ISL signs for better communication for computer‐human interface. This paper narrates a system for automatic recognition of ISL immobile numeric signs, in which a standard digital camera was only used to acquire the signs, no wearable devices are required to capture electrical signals. The system is intended to convert isolated digit signs into text, that is, each entered sign image should contain precisely one numeric sign. To recognize ISL sign images in real time environment, a sign database containing ISL digits is created which contains 5000 images, 500 images for each numeral sign (0‐9). Among two classifiers, the k‐Nearest Neighbor outperforms the Naive Bayes classifier in stipulations of classification accuracy.
Nanotechnology‐Based Approach to Combat Pandemic COVID 19: A Review
Authors: Shukla Brijesh Kumar , Tyagi Himanshi , Bhandari Hema , Garg Seema
Published: June 2021

The emergence of a novel Corona virus (COVID 19) originated on December 19 from China. The city of Wuhan, the capital city of Hubei province, China, is responsible for an outbreak of respiratory illness known as COVID 19 and it has been rapidly spread across the world claiming millions of lives. The sudden outbreak of novel Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2 or 2019‐nCoV), is a big concern for their speedy mitigation using the predictable treatment and creating its approach around the world. Researchers and doctors are in search of rapid diagnosis kit, drugs, and viral‐resistant personal protective equipment (PPE) to clinical diagnosis, medication, and prevent the spread of COVID 19. A rational approach with adaptability and broad viewpoint to challenge the growing pain could be overcome by the application of appropriate technology. The nanotechnology‐based approach can significantly serve the purpose of the current pandemic situation of COVID 19. But same time implementation of innovative and creative nanotech approach, there is a decisive need for the full knowledge of SARS‐CoV‐2 pathogenesis. Moreover, to defeat COVID 19, particularly nanotech‐based system with their viral inhibitory properties to increase the effective nanotech approach is essential. In this scenario, this review aims to summarize the past, present, and future of nanotech‐based systems that can be used to treat COVID 19, highlighting Nano‐based compounds. Lastly, the potential application of the different category of Inorganic Nanomaterials/Inorganic organic conjugate /hybrid system and their practical applicability as suitable means for inspiring against COVID 19 has also been discussed.
Assessing a transmission network of Mycobacterium tuberculosis in an African city using single nucleotide polymorphism threshold analysis
Authors: Yassine Edriss , Galiwango Ronald , Ssengooba Willy , Ashaba Fred , Joloba Moses L. , Zalwango Sarah , Whalen Christopher C. , Quinn Frederick
Published: June 2021

Tuberculosis (TB) is the leading cause of death in humans by a single infectious agent worldwide with approximately two billion humans latently infected with the bacterium Mycobacterium tuberculosis. Currently, the accepted method for controlling the disease is Tuberculosis Directly Observed Treatment Shortcourse (TB‐DOTS). This program is not preventative and individuals may transmit disease before diagnosis, thus better understanding of disease transmission is essential. Using whole‐genome sequencing and single nucleotide polymorphism analysis, we analyzed genomes of 145 M. tuberculosis clinical isolates from active TB cases from the Rubaga Division of Kampala, Uganda. We established that these isolates grouped into M. tuberculosis complex (MTBC) lineages 1, 2, 3, and 4, with the most isolates grouping into lineage 4. Possible transmission pairs containing ≤12 SNPs were identified in lineages 1, 3, and 4 with the prevailing transmission in lineages 3 and 4. Furthermore, investigating DNA codon changes as a result of specific SNPs in prominent virulence genes including plcA and plcB could indicate potentially important modifications in protein function. Incorporating this analysis with corresponding epidemiological data may provide a blueprint for the integration of public health interventions to decrease TB transmission in a region.
Impact of replacing or adding placental growth factor on Down syndrome screening: A prospective cohort study
Authors: Sin Angela Wing To , Poon Liona C. , Chaemsaithong Piya , Wah Yi Man Isabella , Hui Shuk Yi Annie , Ting Yuen Ha , Law Kwok Ming , Leung Tak Yeung , Sahota Daljit Singh
Published: June 2021

Objectives

To assess whether adding placental growth factor (PlGF) or replacing pregnancy‐associated plasma protein‐A (PAPP‐A) improves the first trimester combined test performance for trisomy 21.

Methods

A total of 11,518 women with a singleton pregnancy who underwent the first trimester combined test between December 2016 and December 2019 were included. PlGF was measured and estimated term risk for trisomy 21 was calculated by (1) adding PlGF to the combined test and (2) replacing PAPP‐A with PlGF.

Results

Twenty‐nine pregnancies had trisomy 21. The combined tests detection rate (DR), false positive rate (FPR) and screen positive rate (SPR) were 89.7%, 5.7% and 6% respectively. DR when adding PlGF to the combined test or replacing PAPP‐A remained unchanged. Replacing PAPP‐A by PlGF increased FPR and SPR to 6.2% and 6.4% respectively. Adding PlGF to the combined test gave FPR and SPR rates of 5.5% and 5.7% respectively. Change in FPR and SPR was not significant (p > 0.1 for all).

Conclusion

Adding PlGF to the combined test or replacing PAPP‐A with PlGF did not improve trisomy 21 DR and resulted in a non‐significant marginal change in FPR and SPR.
A constant shear stress strategy for establishing in situ viscosity models of photoinduced polymerization of acrylamide
Authors: Sun Guangdong , Huang Yi , Lv Lingling , Li Dapeng , Fan Qinguo , Li Yongqiang , Shao Jianzhong
Published: June 2021

In situ viscosity kinetics models for blue light induced radical polymerization of acrylamide (AM) were proposed and established with camphorquinone/4‐(dimethylamino)‐2‐ethylbenzoate/diphenyl iodonium hexafluorophosphateas the photoinitiators. In order to minimize the impact of shear effect on polymer network, a constant shear stress technique of photo‐rheometry was proposed to characterize in‐situ viscosity behavior of acrylamide solution during the photopolymerization. The effect of various factors, for example, the dosages of initiator, monomer, and light intensities, on viscosity, polymerization and gelation behavior of AM solution was systematically analyzed. The viscosity advancement behavior was shaped by the joint action of the movement, growth and entanglement of molecular chains, and shear orientation. Different power‐law kinetic models were found in three curves, time‐related viscosity, shear rate‐related viscosity and time‐related shear rate. Such school of thought on constructing the viscosity advancement model provides a new theory and method of systematical studying on the photorheological theories. Furthermore, a trinitarian theoretical model that represented the access from the microscopic kinetics of free radical polymerization to the movement behavior of polymer chains was successfully established by mapping the photoinduced viscosity kinetics model onto the polymerization and crosslinking kinetics model.
Palforzia for desensitisation of peanut allergy in children
Authors: Chaplin Steve
Published: June 2021

Palforzia is an oral defatted peanut powder licensed for desensitisation of peanut allergy in 4–17 year‐olds. This article discusses the dosing procedure, clinical trial efficacy and adverse effects.
A systems pharmacology model for gene therapy in sickle cell disease
Authors: Zheng Bo , Wille Lucia , Peppel Karsten , Hagen David , Matteson Andrew , Ahlers Jeffrey , Schaff James , Hua Fei , Yuraszeck Theresa , Cobbina Enoch , Apgar Joshua F. , Burke John M. , Roberts John , Das Raibatak
Published: June 2021

We developed a mathematical model for autologous stem cell therapy to cure sickle cell disease (SCD). Experimental therapies using this approach seek to engraft stem cells containing a curative gene. These stem cells are expected to produce a lifelong supply of red blood cells (RBCs) containing an anti‐sickling hemoglobin. This complex, multistep treatment is expensive, and there is limited patient data available from early clinical trials. Our objective was to quantify the impact of treatment parameters, such as initial stem cell dose, efficiency of lentiviral transduction, and degree of bone marrow preconditioning on engraftment efficiency, peripheral RBC numbers, and anti‐sickling hemoglobin levels over time. We used ordinary differential equations to model RBC production from progenitor cells in the bone marrow, and hemoglobin assembly from its constituent globin monomers. The model recapitulates observed RBC and hemoglobin levels in healthy and SCD phenotypes. Treatment simulations predict dynamics of stem cell engraftment and RBC containing the therapeutic gene product. Post‐treatment dynamics show an early phase of reconstitution due to short lived stem cells, followed by a sustained RBC production from stable engraftment of long‐term stem cells. This biphasic behavior was previously reported in the literature. Sensitivity analysis of the model quantified relationships between treatment parameters and efficacy. The initial dose of transduced stem cells, and the intensity of myeloablative bone marrow preconditioning are predicted to most positively impact long‐term outcomes. The quantitative systems pharmacology approach used here demonstrates the value of model‐assisted therapeutic design for gene therapies in SCD.
Dense Pt Nanowire Electrocatalyst for Improved Fuel Cell Performance Using a Graphitic Carbon Nitride‐Decorated Hierarchical Nanocarbon Support
Authors: Fang Baizeng , Daniel Lius , Bonakdarpour Arman , Govindarajan Ruben , Sharman Jonathan , Wilkinson David P.
Published: June 2021

An innovative strategy is presented to engineer supported‐Pt nanowire (NW) electrocatalysts with a high Pt content for the cathode of hydrogen fuel cells. This involves deposition of graphitic carbon nitride (g‐CN) onto 3D multimodal porous carbon (MPC) (denoted as g‐CN@MPC) and using the g‐CN@MPC as an electrocatalyst support. The protective coating of g‐CN on the MPC provides good stability for the electrocatalyst support against electrochemical oxidation, and also enhances oxygen adsorption and provides additional active sites for the oxygen reduction reaction. Compared with commercial carbon black Vulcan XC‐72R (denoted as VC) support material, the larger hydrophobic surface area of the g‐CN@MPC enables the supported high‐content Pt NWs to disperse uniformly on the support. In addition, the unique 3D interconnected pore networks facilitate improved mass transport within the g‐CN@MPC support material. As a result, the g‐CN@MPC‐supported high‐content Pt catalysts show improved performance with respect to their counterparts, namely, MPC, VC, and g‐CN@VC‐supported Pt NW catalysts and the conventional Pt nanoparticle (NP) catalyst (i.e., Pt(20 wt%)NPs/VC (Johnson Matthey)) used as the benchmark. More importantly, the g‐CN‐tailored high‐content Pt NW (≈60 wt%) electrocatalyst demonstrates high PEM fuel cell power/performance at a very low cathode catalyst loading (≈0.1 mgPt cm−2).
Comparison between continuous and periodic inspections in step‐stress tests
Authors: Hakamipour Nooshin
Published: June 2021

Accelerated life test is currently the main method of assessing product reliability rapidly, and the design of efficient test plans is a critical step to ensure that accelerated life tests can assess the product reliability accurately, quickly and economically. In these tests, the samples are tested at stress levels higher than normal. Then, the product life at the normal stress level can be estimated by extrapolating the life information of samples at high stress levels to the normal level based on the stress–life relationship. In this paper, optimal k‐level step‐stress accelerated life tests are considered for the Weibull failure data under progressive Type‐I censoring. There are two strategies for performance inspection of the test unit, which include continuous inspection and periodic inspection. These two strategies generate the life data and group data, respectively. In this paper, these two inspection modes are compared and the efficiencies of these are obtained. This paper investigates the optimal design based on five optimality criteria under the constraint that the total experimental cost does not exceed a pre‐specified budget. Finally, based on the simulation study and a real data set, the advantages of using the continuous inspection relative to periodic inspection are investigated.
Bone Histomorphometry and 18F-Sodium Fluoride Positron Emission Tomography Imaging: Comparison Between only Bone Turnover-based and Unified TMV-based Classification of Renal Osteodystrophy
Authors: Aaltonen Louise , Koivuviita Niina , Seppänen Marko , Burton Inari S. , Kröger Heikki , Löyttyniemi Eliisa , Metsärinne Kaj
Published: June 2021

Bone biopsy is the gold standard for characterization of renal osteodystrophy (ROD). However, the classification of the subtypes of ROD based on histomorphometric parameters is not unambiguous and the range of normal values for turnover differ in different publications.18F-Sodium Fluoride positron emission tomography (18F-NaF PET) is a dynamic imaging technique that measures turnover.18F-NaF PET has previously been shown to correlate with histomorphometric parameters. In this cross-sectional study, 26 patients on dialysis underwent a18F-NaF PET and a bone biopsy. Bone turnover-based classification was assessed using Malluche’s historical reference values for normal bone turnover. In unified turnover-mineralization-volume (TMV)-based classification, the whole histopathological picture was evaluated and the range for normal turnover was set accordingly. Fluoride activity was measured in the lumbar spine (L1–L4) and at the anterior iliac crest. On the basis of turnover-based classification of ROD, 12% had high turnover and 61% had low turnover bone disease. On the basis of unified TMV-based classification of ROD, 42% had high turnover/hyperparathyroid bone disease and 23% had low turnover/adynamic bone disease. When using unified TMV-based classification of ROD,18F-NaF PET had an AUC of 0.86 to discriminate hyperparathyroid bone disease from other types of ROD and an AUC of 0.87, for discriminating adynamic bone disease. There was a disproportion between turnover-based classification and unified TMV-based classification. More research is needed to establish normal range of bone turnover in patients with CKD and to establish the role of PET imaging in ROD.