bluuebunny/crossref_metadata_2025 huggingface dataset:
Biotechnological Advances in Detection of Contaminants from Wastewater
Authors: Mehta Hinal , Patel Priya , Mukherjee Anwesha , Munshi Nasreen S.
Published: August 2022

Wastewater from industries causes major environmental pollution problems. The urban development and commercialization in developing countries cause deterioration of surface water resources. Hence, for its improvement, it is essential to develop highly sensitive devices with quick response for monitoring of wastewater contamination. In this respect, biotechnological processes such as biosensors can be promising and a robust option for detection of toxic pollutants. Biosensors can be applied in order to acquire real‐time quantitative data. Nowadays, the enzymes or whole cell bio‐reporters‐based biosensors have promising potential due to the possibility of miniaturization and opportunity for development of in situ biosensors. The growing need of convenient, rapid, and efficient biosensing devices explains the current advancement of biosensors with new transduction materials for multiplexed contaminant detection. Considering the extensive range of sensing strategies including immunochemical‐based, enzymatic and nonenzymatic signals, different kinds of biosensors can be classified as electrochemical, optical, thermal, etc. For the past few years, more attention has been paid to nanomaterial‐based biosensors which exhibit monitoring on the basis of chemical reactions and biological phenomena. Overall, this review focuses on principle and operation (transduction mechanism) of biosensors based on bio‐recognition elements, for the early detection of organic and inorganic contaminants existing in wastewater.
Evaluation of Anticancer Activity of 1,3‐Oxazol‐4‐ylphosphonium Salts in Vitro
Authors: Brusnakov Mykhailo , Golovchenko Olexandr , Velihina Yevheniia , Liavynets Oleksandr , Zhirnov Victor , Brovarets Volodymyr
Published: August 2022

A novel series of 1,3‐oxazol‐4‐yltriphenylphosphonium salts has been synthesized and functionalized. Oxazole derivatives were subjected to NCI in vitro assessment. Seven most active derivatives have been selected for five‐dose assay. Among them, compounds 9 ([2‐(4‐methylphenyl)‐5‐[(4‐methylphenyl)sulfanyl]‐1,3‐oxazol‐4‐yl]triphenylphosphonium perchlorate), 1 ([5‐(4‐methylphenyl)amino]‐2‐phenyl‐1,3‐oxazol‐4‐yl]triphenylphosphonium perchlorate) and 4 ([5‐phenyl‐2‐[(4‐methylphenyl)amino]‐1,3‐oxazol‐4‐yl]triphenylphosphonium perchlorate) were the most active against all tested cancer subpanels. Statistical analysis of the total panel data showed average values of parameters of anticancer activity in the range of 0.3–1.1 μM (GI50), 1.2–2.5 μM (TGI) and 5–6 μM (LC50). It was found that the presence of phenyl or 4‐methylphenyl groups at C(2) and C(5) in the oxazole ring is of critical importance for the manifestation of the anticancer activity. Matrix COMPARE analysis using LC50 vector showed a high positive correlation of compound 9 with standard anticancer agents that can directly disrupt mitochondrial function, causing programmed death of cancer cells. The obtained results indicate the anticancer activity of 1,3‐oxazol‐4‐ylphosphonium salts, which could be useful for developing new anticancer drugs. The most active of them can be recommended for further in‐depth studies and synthesis of new derivatives with antitumor activity on their basis.
Fluorinated Cycloalkyl Building Blocks for Drug Discovery
Authors: Grygorenko Oleksandr O. , Melnykov Kostiantyn P. , Holovach Serhii , Demchuk Oleksandr
Published: August 2022

The review covers various aspects of fluorinated cycloalkyl (C3−C7) building blocks for drug discovery, including their synthesis, key physicochemical properties, and biological and medicinal applications of their derivatives. The discussed synthetic methods include classical nucleophilic fluorinations of various substrates, the addition of fluorine and another heteroatom to double bonds, cycloadditions and other transformations of fluorine‐containing substrates, as well as some newer reactions like fluorination of non‐activated and remotely activated C−H bonds, decarboxylative and deborylative fluorinations, etc. The known data on the effect of introducing the fluorinated cycloalkyl groups on the compound's key in vitro parameters (such as acidity/basicity, lipophilicity, conformational behavior, and short contact capabilities) are surveyed. Finally, applications of fluorinated cycloalkyl building block derivatives in the design of biologically active compounds (including marketed drugs Maraviroc, Ivosidenib, and Sitafloxacin) are covered, with a focus on the fluorination impact.
Discovery of an L‐like Configuration for 3’‐Fluoro‐5’‐norcarbonucleoside Phosphonates as Potent Anti‐HIV Agents
Authors: Geant Pierre‐Yves , Kaci Malika , Uttaro Jean‐Pierre , Périgaud Christian , Mathé Christophe
Published: August 2022

Recently, we reported the racemic synthesis of 3’‐fluoro‐5’‐norcarbocyclic nucleoside phosphonates bearing adenine as the heterocyclic base. For this study, to evaluate the antiviral activity of each enantiomer, we synthesized both enantiomers, as well as their corresponding bis(POM) prodrugs. Anti‐HIV‐1 evaluation against the LAI strain and clinically NRTI‐resistant HIV‐1 strains are presented. The activities against these different strains show that the activities of bis(POM) prodrug (−)‐9 are equivalent or even superior to those of (R)‐PMPA.
Neuropeptide S (NPS) neurons: Parabrachial identity and novel distributions
Authors: Huang Dake , Zhang Richie , Gasparini Silvia , McDonough Miriam C. , Paradee William J. , Geerling Joel C.
Published: August 2022

Neuropeptide S (NPS) increases wakefulness. A small number of neurons in the brainstem express Nps. These neurons are located in or near the parabrachial nucleus (PB), but we know very little about their ontogeny, connectivity, and function. To identify Nps‐expressing neurons within the molecular framework of the PB region, we used in situ hybridization, immunofluorescence, and Cre‐reporter labeling in mice. The primary concentration of Nps‐expressing neurons borders the lateral lemniscus at far‐rostral levels of the lateral PB. Caudal to this main cluster, Nps‐expressing neurons scatter through the PB and form a secondary concentration medial to the locus coeruleus (LC). Most Nps‐expressing neurons in the PB region are Atoh1‐derived, Foxp2‐expressing, and mutually exclusive with neurons expressing Calca or Lmx1b. Among Foxp2‐expressing PB neurons, those expressing Nps are distinct from intermingled subsets expressing Cck or Pdyn. Examining Nps Cre‐reporter expression throughout the brain identified novel populations of neurons in the nucleus incertus, anterior hypothalamus, and lateral habenula. This information will help focus experimental questions about the connectivity and function of NPS neurons.
Prediction and forecasting of worldwide corona virus (COVID‐19) outbreak using time series and machine learning
Authors: Jain Priyank , Sahu Shriya
Published: August 2022

How will the newly discovered coronavirus (COVID‐19) affect the world and what will be its global impact? For answering this question, we will require a prediction of overall recoveries and fatalities, as well as a reliable prognosis of coronavirus cases. Predicting, however, requires an ample total of past data related to it. On any particular day, the prediction is unclear since events in the future rarely repeat themselves the way that they did in the past. Furthermore, forecasts and predictions are determined by the absolute interests, accuracy of the data, and prophesied variables. In addition, psychological factors play an enormous role in how people perceive and react to the danger from the disease and therefore the fear that it is going to affect them personally. This research paper advances an unbiased method for predicting the increase of the COVID‐19 employing a simple, but powerful method to do so. Assumed that the data are accurate and reliable which the longer term will still follow an equivalent disease pattern, our projections intimate with a large association. Within the COVID‐19 cases were documented, in contingency, there is a steady increase. The hazards are far away from symmetric, as underestimating a pandemic's spread and failing to do enough to prevent it is far a lot worse than overspending and being too cautious when it will not be needed. This paper illustrates the timeline of a live forecasting study with huge implied implications for devising and decision‐making and gives unbiased predictions on COVID‐19 confirmed cases, recovered cases, deaths, and ongoing cases are shown on a continental map using data science and machine learning (ML) approaches. Utilizing these ML‐based techniques, the proposed system predicts the accurate COVID‐19 cases and gives better performance.
Corporate social responsibility and green behaviour: Towards sustainablefood‐businessdevelopment
Authors: Shiri Nematollah , Jafari‐Sadeghi Vahid
Published: August 2022

Literature in the field of corporate social responsibility (CSR) has mainly focused on customers, particularly on their loyalty, behavioural intent and satisfaction. That is, the effectiveness of CSR dimensions has been less considered by scholars. Hence, this research strives to explore the effect of CSR dimensions on the green behaviour among employees of food businesses in Iran. In this vein, the mediating role of green trust and the moderating role of gender in the relationship between the CSR dimensions and the green behaviour of employees have been investigated. The samples of this research included 415 employees of food businesses and companies in Iran. The findings reveal that the CSR dimensions (economic CSR, ethical CSR and philanthropic CSR) directly and indirectly—through the mediating variable of green trust—played an important role in shaping the green behaviour of employees. In this study, the direct and indirect effects of legal CSR on green behaviour among employees were not confirmed. Furthermore, the results represent that the gender variable moderates the effect of the CSR dimensions on the green behaviour of employees, highlighting that economic CSR and ethical CSR played a prominent role in shaping the green behaviour of respectively males and females. In addition, the theoretical and practical implications of the research discussed the impact of green behaviour on producing environmentally friendly products in order to sustainable development in the food business.
Influence of early social isolation on general activity and spatial learning in adult WAG/Rij rats
Authors: Shishelova Anna Y. , Smirnov Kirill , Raevskiĭ Vladimir V.
Published: August 2022

The study identifies the critical period of early ontogeny, during which social factors have the greatest influence on the operant behavior with positive reinforcement in adult WAG/Rij rats. Individual social isolation of rats from dam and siblings was performed daily for 3 h during postnatal day (PND) 2–8, 9–15, and 16–22. General activity and water consumption were examined using the IntelliCage (IC) in adulthood. The operant behavior training was performed in four consecutive sessions: free exploration of the IC environment (adaptation), learning to retrieve water by nosepoking (nosepoke adaptation), spatial learning to retrieve water in the specific corner (place learning), and retraining with a change of a place preference (reversal learning). Social isolation during PND16–22 led to the greatest behavioral changes in all sessions of the experiment. These rats were more active, consumed more water, demonstrated a higher ratio of visits with drinking to the total number, and relearned faster after changing the location of the rewarded corner. Thus, the postnatal period between days 16 and 22 in WAG/Rij rat pups is more sensitive to social isolation for change of adaptive behavior in the IC in adulthood.
Engineering current collectors for advanced alkali metal anodes: A review and perspective
Authors: Hu Liang , Deng Jiaojiao , Liang Qinghua , Wu Junxiong , Ge Bingcheng , Liu Qiang , Chen Guohua , Yu Xiaoliang
Published: August 2022

Alkali metal batteries (AMBs) are promising next‐generation high‐density electrochemical energy storage systems. In addition, current collectors play important roles in enhancing their electrochemical performances. Thus, it is essential to have a critical review of the most recent advances in engineering the current collectors for high‐performance AMBs. In this review paper, the fundamentals of alkali metal deposition on current collectors will be introduced first. Then recent advances in the development of advanced metal and carbon‐based current collectors are examined for boosting the stability and cycle life of lithium metal batteries (LMBs) in terms of various strategies including 3D architectural design and functional modifications. Thereafter, the research progress in design of advanced current collectors will be analyzed for sodium/potassium metal batteries, especially the counterparts that do not follow the paradigms established in LMBs. Finally, the major challenges and key perspectives will be discussed for the future development of current collectors in AMBs.

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Mapping the effect of plant‐based extracts on immune and tumor cells from a bioactive compound standpoint
Authors: Huang Chujun , Xu Tianxiong , Li Yanping , Ren Jiaoyan
Published: August 2022

Instead of traditional regimen of “one molecule, one target, one disease,” natural plant extracts, as a multi‐component system, show great potential in alleviate disease with complex etiology and pathophysiological factors, such as cancer. In this study, we evaluated the chemical characteristic as well as bioactive activities profiles of 15 species of plant‐based extracts, which corresponding to polysaccharide, protein, polyphenol content, and effects on MC38, LLC, RAW264.7 cell viability, respectively. Person correlation analysis and multi‐criteria decision analysis method was proposed to evaluate dose‐effect relationship and the comprehensive activities of each extract. A significant positive correlation was found between polyphenol value and immune cell activity, which means that it was considered to perform well on antitumor and immunomodulatory effects when compared to the studied substances. The subsequent measurement by a MC38‐N4/OT‐I coculture model verified the results, showing an excellent effect of Grifola frondosa on enhancing the antigen‐specific killing of tumor cells. Here we give a general view of the chemical composition and the bioactive activities of 15 plant‐based extracts and provide a feasible strategy to estimate the complex effect of phytochemicals. That would help us to better understand the effect of phytochemical combination and lay a good foundation for further in vivo studies.
Rapid in vivo multiplexed editing (RIME) of the adult mouse liver
Authors: Katsuda Takeshi , Cure Hector , Sussman Jonathan , Simeonov Kamen P. , Krapp Christopher , Arany Zoltan , Grompe Markus , Stanger Ben Z.
Published: August 2022

Background and Aims:

Assessing mammalian gene function in vivo has traditionally relied on manipulation of the mouse genome in embryonic stem cells or perizygotic embryos. These approaches are time‐consuming and require extensive breeding when simultaneous mutations in multiple genes is desired. The aim of this study is to introduce a rapid in vivo multiplexed editing (RIME) method and provide proof of concept of this system.

Approach and Results:

RIME, a system wherein CRISPR/caspase 9 technology, paired with adeno‐associated viruses (AAVs), permits the inactivation of one or more genes in the adult mouse liver. The method is quick, requiring as little as 1 month from conceptualization to knockout, and highly efficient, enabling editing in >95% of target cells. To highlight its use, we used this system to inactivate, alone or in combination, genes with functions spanning metabolism, mitosis, mitochondrial maintenance, and cell proliferation.

Conclusions:

RIME enables the rapid, efficient, and inexpensive analysis of multiple genes in the mouse liver in vivo.
Zinc oxide nanoclusters and their potential application as CH4 and CO2 gas sensors: Insight from DFT and TD‐DFT
Authors: Muz İskender , Kurban Mustafa
Published: August 2022

We have investigated the adsorption of CH4 and CO2 gases on zinc oxide nanoclusters (ZnO NCs) using density functional theory (DFT). It was found that the CH4 tends to be physically adsorbed on the surface of all the ZnO NCs with adsorption energy in the range −11 to −14 kcal/mol. Even though, the CO2 is favorably chemisorbed on the Zn12O12 and Zn15O15 NCs, with adsorption energy about −38 kcal/mol at B3LYP/6‐311G(d,p) level of theory. When the CH4 and CO2 gases are adsorbed on the ZnO NCs, their electrical conductivities are decreased, and thus the studied ZnO NCs do not generate an electrical signal in the presence of CH4 and CO2 gases. Interestingly, both pure and gas adsorbed Zn22O22 NC exhibited more favorable electronic and reactive properties than other NCs. Comparison of the structural, electronic, and optical data predicted by DFT/B3LYP and TD‐DFT/CAM‐B3LYP calculations with those experimentally obtained show good agreement.
The diagnostic importance of multiple cytokines in adult hemophagocytic lymphohistiocytosis
Authors: Jin Zhili , Suolitiken Dina , Wang Yini , Wang Zhao
Published: August 2022

Background

Hemophagocytic lymphohistiocytosis (HLH) is a category of immunological illnesses that cause out‐of‐control T cells and macrophages to release life‐threatening cytokines. The HLH‐2004 diagnostic criteria are the gold standard for HLH diagnosis, but there is a need to investigate the usefulness of various cytokines for HLH diagnosis.

Methods

Patients admitted to Beijing Friendship Hospital of Capital Medical University from January 2016 to December 2020 were included in this retrospective study, with 166 patients with confirmed HLH and 142 febrile patients requiring differential diagnosis completing the sum. Multiplex cytokine assays using multifactor liquid phase microarray technology‐based multifactor liquid phase microarray technology were used to detect 33 cytokines. Twenty‐eight cytokines detected using the Luminex analytical platform technology were ultimately included in the analysis.

Results

Interleukin‐1 receptor antagonist (IL‐1 RA), IL‐18, interferon‐γ (IFN‐γ), and interferon‐induced protein 10 (IP‐10) regulated upon activation normal T cell expressed and secreted (RANTES), eotaxin, growth‐related oncogene α (GRO‐α), and macrophage inflammatory protein‐1 α (MIP‐1α) were higher in the HLH group than in the non‐HLH group, and the differences were statistically significant. Among them, the area under the curve (AUC) for IL‐18 for HLH diagnosis was reported for the first time as 82.69%, with a sensitivity of 76.32% and a specificity of 79.61%; the AUC of IL‐1 RA was 72.34%, with a sensitivity of 62.71% and a specificity of 75.97%; and the AUC of IP‐10 was 71.73%, with a sensitivity of 60.14% and a specificity of 75.15%. Moreover, the AUC of the combined diagnostic tests for IL‐1 RA, IL‐18, IFN‐γ, IP‐10, and RANTES was 99.6%, with a sensitivity of 95.8% and a specificity of 98.6%.

Conclusion

Our study concluded that multiple cytokines are valid biological markers for the diagnosis of HLH. The findings of this study remain to be validated in an external dataset.
Coinfections with multiple sexually transmitted pathogens in Republic of Korea, 2018–2020
Authors: Lee Sun Jung , Jang Tae Su , Jeon Jae‐Sik , Kim Jae Kyung
Published: August 2022

Background

Sexually transmitted infections (STIs) can have serious consequences, and the global STI incidence remains high. However, there is little information on the frequency of STIs with multiple pathogens according to age. Accordingly, we conducted a study to determine the trends of coinfection with sexually transmitted pathogens according to age in the Republic of Korea from 2018 to 2020.

Methods

From January 2018 to December 2020, 65,191 samples of swab, urine, and other types submitted for STI screening were obtained from U2Bio Co. Ltd. (Seoul, Republic of Korea). Multiplex polymerase chain reaction, a sensitive and rapid method for simultaneous detection of STIs caused by multiple different pathogens, was performed using an AccuPower STI4C‐Plex Real‐Time PCR kit, AccuPower STI8A‐Plex Real‐Time PCR kit, and AccuPower STI8B‐Plex Real‐Time PCR kit with an Exicycler 96 Real‐Time Quantitative Thermal Block.

Results

Of the 65,191 samples tested, 35,366 (54.3%) tested positive for one or more sexually transmitted pathogens. The prevalence of coinfections with two or more sexually transmitted pathogens was inversely proportional to age. Furthermore, the rates of coinfection with sexually transmitted pathogens and age distribution differed according to sex and the sexually transmitted pathogen type.

Conclusion

This study confirmed that a significant proportion of patients with STIs are coinfected with multiple pathogens. Public health managers could use these results to recognize and prevent STIs according to age.
Is there a potential biomarker in distinguishing invasive breast carcinomas with elevated Ki‐67 levels among 2D‐SWE, SMI, and 18F‐FDG PET‐CT/MRI‐derived parameters?: A single‐center data
Authors: Kurt Seda Aladag , Besli Lebriz Uslu , Kayadibi Yasemin , Samanci Cesur , Nazari Azizullah , Ozturk Tulin , Kocael Pinar , Sayman Haluk
Published: August 2022

Purpose

To investigate the strength of quantitative imaging and metabolic parameters in differentiating invasive breast carcinomas with elevated Ki‐67 levels.

Materials and Methods

A total of 123 patients with 129 breast lesions confirmed as invasive breast carcinoma underwent shear wave elastography (SWE), superb microvascular imaging (SMI) and positron emission tomography (PET)/CT or MRI. Adler's grade (classifying the microvascularity into four types) and Vascular Index (VI) was obtained by SMI as microvascular parameters. In addition, the stiffness value (Emean) was evaluated in kilopascal by SWE. The average of consecutive measurements was recorded as mean VI and mean Emean. PET scan parameters were obtained as SUVmax and SULpeak. Lesions were divided into two groups according to the Ki‐67 expression, low as 14 and high as >14.

Results

Adler's grading was the most correlated imaging parameter with high Ki‐67 expression (p < 0.05), while VI and Emean had poor correlation (p > 0.05). SUVmax and SULpeak indicated a significant linear correlation with Ki‐67 but a moderate correlation with the high levels of Ki‐67 (p < 0,001). The sensitivity of VI, Emean, SUVmax and SULpeak was 64.6%, 66.7%, 65.7%, and 66.7% when the cut‐off point was set to 5.25, 102.5, 6.59, and 2.63, respectively. SUVmax had the highest AUC value of 0.740, according to the ROC curve analysis.

Conclusions

Our results suggest that the quantitative parameters obtained by advanced imaging methods may be useful in predicting the high proliferation in invasive breast carcinomas. But none of them is eligible to be used as an independent biomarker in distinguishing aggressive behavior. Nevertheless, as a noninvasive method, visual assessment of microvascular morphology using SMI increases the prognostic efficiency in invasive breast carcinomas.
Meta‐analysis of the demographic and prognostic significance of gastrointestinal symptoms in COVID‐19 patients
Authors: Zaman Shafquat , Hajibandeh Shahin , Hajibandeh Shahab , Mohamedahmed Ali Yasen Y , El‐Asrag Mohammed E , Quraishi Nabil , Iqbal Tariq H , Beggs Andrew D
Published: August 2022

Background and Aim

To evaluate the demographic and prognostic significance of gastrointestinal (GI) symptoms in patients with coronavirus disease 2019 (COVID‐19).

Methods

A systematic search of electronic information sources was conducted. Combined overall effect sizes were calculated using random‐effects models for baseline demographic factors and outcomes including mortality, intensive care unit (ICU) admission, and length of hospital stay.

Results

Twenty‐four comparative observational studies reporting a total of 51 522 COVID‐19 patients with (n = 6544) or without (n = 44 978) GI symptoms were identified. The patients with GI symptoms were of comparable age (mean difference [MD]: 0.25, 95% confidence interval [CI] −2.42 to 2.92, P = 0.86), rate of pre‐existing hypertension (odds ratio [OR]: 1.11, 95% CI 0.86–1.42, P = 0.42), diabetes mellitus (OR: 1.14, 95% CI 0.91–1.44, P = 0.26), and coronary artery disease (OR: 1.00, 95% CI 0.86–1.16, P = 0.98) compared with those without GI symptoms. However, there were significantly more male patients in the GI symptoms group (OR: 0.85, 95% CI 0.75–0.95, P = 0.005). The presence of GI symptoms was associated with similar risk of mortality (OR: 0.73; 95% CI 0.47–1.13, P = 0.16), ICU admission (OR: 1.15; 95% CI 0.67–1.96, P = 0.62), and length of hospital stay (MD: 0.43; 95% CI −0.73 to 1.60, P = 0.47) when compared with their absence.

Conclusion

Meta‐analysis of the best possible available evidence demonstrated that GI symptoms in COVID‐19 patients do not seem to affect patients with any specific demographic patterns and may not have any important prognostic significance. Although no randomized studies can be conducted on this topic, future high‐quality studies can provide stronger evidence to further understand the impact of GI symptoms on outcomes of COVID‐19 patients.
Synthetic attempts toward α‐tocopherol—An overview
Authors: Kundu Subhradip , Sarkar Debayan
Published: August 2022

The discovery of vitamin E as an essential factor in the diet was a scientific revolution that enlightened the entire world. Vitamin E was discovered in the year 1922 by Herbert M. Evans and K. Scott Bishop and the first synthetic attempt toward α‐tocopherol appeared almost two decades later through a condensation reaction. During the second world war, similar Lewis acid‐catalyzed condensation approaches were accomplished starring 1,3,5‐trimethyl hydroquinone and varying the other component. The stereochemistry of the three chiral centers present in the α‐tocopherol molecule was revealed in the early 1960s and thereafter scientific community took interest in synthesizing natural (2R,4′R,8′R)‐α‐tocopherol molecule with high enantioselectivity. During the first decade of the 21st century, several groups have applied Brønsted and Lewis acid catalysts to mobilize the condensation reactions toward α‐tocopherol. In the year 2012, we celebrated 100 years of vitamins and now we are celebrating the 100th anniversary of vitamin E discovery. This historical review highlights key research achievements since the last century and untold stories on α‐tocopherol and/or vitamin E.
Derivation of a clinical‐based model to detect invasive bacterial infections in febrile infants
Authors: Yaeger Jeffrey P. , Jones Jeremiah , Ertefaie Ashkan , Caserta Mary T. , Fiscella Kevin A.
Published: August 2022

Background

Febrile infants are at risk for invasive bacterial infections (IBIs) (i.e., bacteremia and bacterial meningitis), which, when undiagnosed, may have devastating consequences. Current IBI predictive models rely on serum biomarkers, which may not provide timely results and may be difficult to obtain in low‐resource settings.

Objective

The aim of this study was to derive a clinical‐based IBI predictive model for febrile infants.

Designs, Setting, and Participants

This is a cross‐sectional study of infants brought to two pediatric emergency departments from January 2011 to December 2018. Inclusion criteria were age 0–90 days, temperature ≥38°C, and documented gestational age, fever duration, and illness duration.

Main Outcome and Measures

To detect IBIs, we used regression and ensemble machine learning models and evidence‐based predictors (i.e., sex, age, chronic medical condition, gestational age, appearance, maximum temperature, fever duration, illness duration, cough status, and urinary tract inflammation). We up‐weighted infants with IBIs 8‐fold and used 10‐fold cross‐validation to avoid overfitting. We calculated the area under the receiver operating characteristic curve (AUC), prioritizing a high sensitivity to identify the optimal cut‐point to estimate sensitivity and specificity.

Results

Of 2311 febrile infants, 39 had an IBI (1.7%); the median age was 54 days (interquartile range: 35–71). The AUC was 0.819 (95% confidence interval: 0.762, 0.868). The predictive model achieved a sensitivity of 0.974 (0.800, 1.00) and a specificity of 0.530 (0.484, 0.575). Findings suggest that a clinical‐based model can detect IBIs in febrile infants, performing similarly to serum biomarker‐based models. This model may improve health equity by enabling clinicians to estimate IBI risk in any setting. Future studies should prospectively validate findings across multiple sites and investigate performance by age.
Thermodynamic and structural profiles of multi‐target binding of vinblastine in solution
Authors: Gopi Priyanka , Singh Shweta , Islam Md Maidul , Yadav Akankasha , Gupta Neelima , Pandya Prateek
Published: August 2022

Structural information about drug‐receptor interactions is paramount in drug discovery and subsequent optimization processes. Drugs can bind to multiple potential targets as they contain common chemical entities in their structures. Understanding the details of such interactions offer possibilities for repurposing and developing potent inhibitors of disease pathways. Vinblastine (VLB) is a potent anticancer molecule showing multiple receptor interactions with different affinities and degrees of structural perturbations. We have investigated the multi‐target binding profile of VLB with DNA and human serum albumin (HSA) in a dynamic physiological environment using spectroscopic, molecular dynamics simulations, and quantum mechanical calculations to evaluate the structural features, mode, ligand and receptor flexibility, and energetics of complexation. These results confirm that VLB prefers to bind in the major groove of DNA with some inclination toward Thymidine residue and the TR‐5 binding site in HSA with its catharanthine half making important contacts with both the receptors. Spectroscopic investigation at multiple temperatures has also proved that VLB binding is entropy driven indicating the major groove and TR‐5 binding site of interaction. Finally, the overall binding is facilitated by van der Waals contacts and a few conventional H‐bonds. VLB portrays reasonable conformational diversity on binding with multiple receptors.
Different Imaging Modalities for the Diagnosis of Axillary Lymph Node Metastases in Breast Cancer: A Systematic Review and Network Meta‐Analysis of Diagnostic Test Accuracy
Authors: Li Zhifan , Gao Ya , Gong Hengxin , Feng Wen , Ma Qinqin , Li Jinkui , Lu Xingru , Wang Xiaohui , Lei Junqiang
Published: August 2022

Background

Accurate diagnosis of axillary lymph node metastasis (ALNM) of breast cancer patients is important to guide local and systemic treatment.

Purpose

To evaluate the diagnostic performance of different imaging modalities for ALNM in patients with breast cancer.

Study Type

Systematic review and network meta‐analysis (NMA).

Subjects

Sixty‐one original articles with 8011 participants.

Field Strength

1.5 T and 3.0 T.

Assessment

We used the QUADAS‐2 and QUADAS‐C tools to assess the risk of bias in eligible studies. The identified articles assessed ultrasonography (US), MRI, mammography, ultrasound elastography (UE), PET, CT, PET/CT, scintimammography, and PET/MRI.

Statistical Analysis

We used random‐effects conventional meta‐analyses and Bayesian network meta‐analyses for data analyses. We used sensitivity and specificity, relative sensitivity and specificity, superiority index, and summary receiver operating characteristic curve (SROC) analysis to compare the diagnostic value of different imaging modalities.

Results

Sixty‐one studies evaluated nine imaging modalities. At patient level, sensitivities of the nine imaging modalities ranged from 0.27 to 0.84 and specificities ranged from 0.84 to 0.95. Patient‐based NMA showed that UE had the highest superiority index (5.95) with the highest relative sensitivity of 1.13 (95% confidence interval [CI]: 0.93–1.29) among all imaging methods when compared to US. At lymph node level, MRI had the highest superiority index (6.91) with highest relative sensitivity of 1.13 (95% CI: 1.01–1.23) and highest relative specificity of 1.11 (95% CI: 0.95–1.23) among all imaging methods when compared to US. SROCs also showed that UE and MRI had the largest area under the curve (AUC) at patient level and lymph node level of 0.92 and 0.94, respectively.

Data Conclusion

UE and MRI may be superior to other imaging modalities in the diagnosis of ALNM in breast cancer patients at the patient level and the lymph node level, respectively. Further studies are needed to provide high‐quality evidence to validate our findings.

Evidence Level

3

Technical Efficacy

Stage 2
The use of virtual interviews and new trends in orthopedic surgery residency match
Authors: Metrione Michael D. , Hreha Jeremy , Soussou Thomas , Hanna Gabriel , Vosbikian Michael
Published: August 2022

This retrospective cross‐sectional study sought to determine if there was a change in geographical trends in the orthopedic surgery residency match with the use of virtual interviews. Due to the COVID‐19 pandemic, visiting rotations at outside institutions were restricted and all residency interviews were conducted virtually for the 2021 match. Given these restrictions, it was hypothesized that applicants would match at a higher rate to their medical school‐affiliated residency programs, or geographically nearby their medical school. Data was collected from residency program website and social media accounts to determine if the use of virtual interviews correlated with a decreased rate of matching at outside institutions. During the 2021 match, applicants who applied to orthopedic surgery in 2021 were more likely to match at their medical school‐affiliated institution (OR, 1.46; 95% CI, 1.18–1.80; p < 0.01) compared to applicants during previous years. However, match rates were not different in terms of geographical regions. Virtual interviews are more cost‐effective for both applicants and programs, however, this study demonstrates there are associated changes with this new interview structure. The utility of virtual interviews as a standard method in the future should take this change in trend into consideration.
Clinical applications of body composition and functional status tools for nutrition assessment of hospitalized adults: A systematic review
Authors: Smith Luke O. , Olieman Joanne F. , Berk Kirsten A. , Ligthart‐Melis Gerdien C. , Earthman Carrie P.
Published: August 2022

Background

No global consensus exists on diagnostic criteria for malnutrition. Muscular deficits and functional impairments are major components of available malnutrition diagnostic frameworks because these facets of nutrition status significantly impact outcomes. The purpose of this review is to explore which body composition assessment (BCA) and functional status assessment (FSA) tools are being used for nutrition assessment (NA) and monitoring the response to nutrition interventions (RNIs) in adult inpatients.

Methods

A literature search of Embase, Medline (Ovid), Web of Science, and Cochrane Central was performed to identify studies that used BCA and/or FSA tools for NA (along with an accepted NA diagnostic framework) and/or for monitoring RNI in adult inpatients.

Results

The search yielded 3667 articles; 94 were included in the review. The number of studies using BCA and/or FSA tools for NA was 47 and also 47 for monitoring RNI. Seventy‐nine percent of studies used bioimpedance for BCA, and 97% that included FSA utilized handgrip strength. When compared against sets of diagnostic criteria, many of the BCA and FSA tools showed promising associations with nutrition status.

Conclusion

Bioimpedance methods are the most widely used bedside BCA tools, and handgrip strength is the most widely used FSA tool; however, these methods are being used with a variety of protocols, algorithms, and interpretation practices in heterogeneous populations. To create a standardized nutrition status assessment process there is a need for validation studies on bedside methods and the development of globally standardized assessment protocols in clinical inpatient settings.
Development of non‐destructive analytical strategies based on Raman spectroscopy and complementary techniques for Mars Sample Return tested on Northwest Africa 1950 Martian meteorite
Authors: Coloma Leire , García‐Florentino Cristina , Huidobro Jennifer , Torre‐Fdez Imanol , Aramendia Julene , Arana Gorka , Castro Kepa , Madariaga Juan Manuel
Published: August 2022

The Mars Sample Return (MSR) is a near future mission to return samples from the surface of Mars to the Earth. The field operations to carry out data collection, selection of the samples, and sampling procedure, mainly related to the CanMars MSR analog mission, are well‐studied and published. In contrast, studies related to the methodology implemented to characterize the mineralogy of the returned samples are scarcer and focused on biosignature detection. This work presents a non‐destructive analytical methodology based on Raman microscopy (single point and imaging), micro‐energy dispersive X‐ray fluorescence imaging analysis, and scanning electron microscopy coupled to energy dispersive spectroscopy that could be used as a first analytical characterization for the Martian samples that will be returned to the Earth in the upcoming MSR mission, before any destructive analysis. The analytical methodology has been tested on a fragment of the Northwest Africa 1950 Martian meteorite, which gives us a mineralogical characterization of the meteorite. This methodology also allowed to define several chemical reactions taking place in some of the mineral phases (olivines and ilmenite) of the meteorite. In addition to the geochemical characterization of the samples, the fact that this methodology allows to assess the chemical transformations in several minerals gives important clues for describing mineral processes and geological evolution that took place on Mars. This work also shows the advantages and disadvantages that each of the techniques employed has when performing a mineralogical characterization, the information that each one can provide and the importance of combining them.
Using Item‐Response Theory to Improve Interpretation of the Trans Woman Voice Questionnaire
Authors: Zhao Nina W. , Mason James M. , Blum Alexander M. , Kim Eric K. , Young VyVy N. , Rosen Clark A. , Schneider Sarah L.
Published: August 2022

Objective

The Trans Woman Voice Questionnaire (TWVQ) is commonly used to quantify self‐perceptions of voice for trans women seeking gender‐affirming voice care, but the interpretation of TWVQ scores remains challenging. The objective of this study was to use item‐response theory (IRT) to evaluate the relationship between TWVQ items and persons on a common scale and identify improvements to increase the meaningfulness of TWVQ scores.

Methods

A retrospective review of TWVQ scores from trans women patients between 2018–2020 was performed. Rasch‐family models were used to generate item‐person maps positioning respondent location and item difficulty estimates on a logit scale, which was then converted into a scaled score using linear transformations.

Results

TWVQ responses from 86 patients were analyzed. Initial item‐person maps demonstrated that the middle response categories (“sometimes” and “often”) performed inconsistently across items (poor threshold banding); interpretability improved when these ratings were scored as one category. The models were rerun using revised scoring, which retained high reliability (0.93) and supported a unidimensional construct. Updated item‐person maps revealed four scaled score zones (≤54, >54 to ≤101, >101 to ≤140, and >140) that each corresponded to an increasing pattern of item thresholds (probability of selecting one response category vs. others). These ranges can be interpreted as minimal, low, moderate, and high, respectively.

Conclusions

Empiric data from Rasch analysis supports new interval scoring for the TWVQ that advances the clinical and research utility of the instrument and lays the foundation for future improvements in clinical care and outcomes assessment.

Level of Evidence

NA Laryngoscope, 133:1197–1204, 2023
Development of core collections in soybean on the basis of seed size
Authors: Nair Ramakrishnan M. , Yan Miao‐rong , Vemula Anil Kumar , Rathore Abhishek , van Zonneveld Maarten , Schafleitner Roland
Published: August 2022

Core collections display a large fraction of the diversity contained in large collections in smaller germplasm panels. We used historical data (1973–2015) collected at the World Vegetable Center, Taiwan, for developing soybean (Glycine max L. Merr.) core collections representing the diversity of the whole collection of 7853 accessions held by the Center. The collection was split into two groups on the basis of the 100 seed weight: large seeded (>25 g or equal to 25 g) and small seeded (<25 g). The large‐seeded group (vegetable soybean/edamame) comprised 456 accessions, while the small‐seeded group contained 7397 accessions. Within these two groups, we developed core collections based on seven quantitative and 14 qualitative traits collected during the autumn season, resulting in a core collection of 112 large‐seeded vegetable soybean accessions and 1480 accessions for the small‐seeded types.
Biogeochemical‐Argo data suggest significant contributions of small particles to the vertical carbon flux in the subpolar North Atlantic
Authors: Wang Bin , Fennel Katja
Published: August 2022

The biological carbon pump exerts a strong control on atmospheric CO2 levels. It includes a range of processes that generate organic carbon in the surface ocean and transport this organic matter from the surface to the deep ocean where it is remineralized and sequestered as inorganic carbon for decades to millennia. While ocean productivity is relatively well observed through a combination of approaches including remote sensing, the magnitude of vertical carbon transport remains poorly constrained by observations and the detailed processes involved are insufficiently understood. In particular, attention to the contribution of small particles has increased in recent years, but previous estimates of the associated vertical carbon flux have ignored remineralization and particle fragmentation. The resulting estimates are likely biased. In this study, we present a method for estimating (1) vertical carbon flux of two different size classes of organic particles and (2) the effect of remineralization and particle fragmentation on mesopelagic flux attenuation using Biogeochemical‐Argo profiles of backscattering and dissolved oxygen. We applied this method to observations from the subpolar North Atlantic and found that, on annual timescales, gravitational settling of large organic particles is dominating the vertical flux through the lower mesopelagic zone. However, small particles contribute significantly to the vertical carbon flux at 100 m (around 36% but can be up to 63%), via different mechanisms, and at 600 m (0–25%) since they can be produced by the fragmentation within the mesopelagic zone.
Identifying Protective Drugs for Parkinson's Disease in Health‐Care Databases Using Machine Learning
Authors: Courtois Émeline , Nguyen Thi Thu Ha , Fournier Agnès , Carcaillon‐Bentata Laure , Moutengou Élodie , Escolano Sylvie , Tubert‐Bitter Pascale , Elbaz Alexis , Thiébaut Anne C.M. , Ahmed Ismaïl
Published: August 2022

Background

Available treatments for Parkinson's disease (PD) are only partially or transiently effective. Identifying existing molecules that may present a therapeutic or preventive benefit for PD (drug repositioning) is thus of utmost interest.

Objective

We aimed at detecting potentially protective associations between marketed drugs and PD through a large‐scale automated screening strategy.

Methods

We implemented a machine learning (ML) algorithm combining subsampling and lasso logistic regression in a case–control study nested in the French national health data system. Our study population comprised 40,760 incident PD patients identified by a validated algorithm during 2016 to 2018 and 176,395 controls of similar age, sex, and region of residence, all followed since 2006. Drug exposure was defined at the chemical subgroup level, then at the substance level of the Anatomical Therapeutic Chemical (ATC) classification considering the frequency of prescriptions over a 2‐year period starting 10 years before the index date to limit reverse causation bias. Sensitivity analyses were conducted using a more specific definition of PD status.

Results

Six drug subgroups were detected by our algorithm among the 374 screened. Sulfonamide diuretics (ATC‐C03CA), in particular furosemide (C03CA01), showed the most robust signal. Other signals included adrenergics in combination with anticholinergics (R03AL) and insulins and analogues (A10AD).

Conclusions

We identified several signals that deserve to be confirmed in large studies with appropriate consideration of the potential for reverse causation. Our results illustrate the value of ML‐based signal detection algorithms for identifying drugs inversely associated with PD risk in health‐care databases. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
A Scaffold‐based Deep Generative Model Considering Molecular Stereochemical Information
Authors: Xu Tianxu , Wang Minjun , Liu Xiaoqian , Feng Dawei , Zhu Yanjuan , Fan Zhe , Rao Shurong , Lu Jing
Published: August 2022

Designing molecules with specific scaffolds can facilitate the discovery and optimization of lead compounds. Some scaffold‐based molecular generation models have been developed using deep‐learning methods based on specific scaffolds, although incorporating scaffold generalization is expected to achieve scaffold hopping. Moreover, most of the existing models focus on the 2D shape of the scaffold and overlook the stereochemical properties of the compound, especially for natural products. In this study, we optimized the scaffold‐based molecular generation model designed by Lim et al. (Chemical Science 2020, 11, 1153–1164). Real‐time ultrafast shape recognition with pharmacophore constraints (USRCAT) was introduced into the model to search for molecules similar to the 3D conformation and pharmacophore of the input scaffold sourced from the training set; the searched molecules were then used as new scaffolds to execute scaffold hopping. The optimized model could generate new molecules with the same chirality as the input scaffold. Furthermore, the probability distribution of the molecular structure and various physicochemical properties were analyzed to evaluate the model's generation capability. We thus believe that the optimized model can provide a basis for medicinal chemists to explore a wider chemical space toward optimization of the lead compounds and to screen the virtual compound library.