bluuebunny/crossref_metadata_2025 huggingface dataset:
Is my doctor around me? Investigating the impact of doctors’ presence on patients’ review behaviors on an online health platform
Authors: Liu Xiaoxiao , Hu Mingye , Xiao Bo Sophia , Shao Jingbo
Published: February 2022

Patient‐generated online reviews are well‐established as an important source of information for people to evaluate doctors' quality and improve health outcomes. However, how such reviews are generated in the first place is not well examined. This study examines a hitherto unexplored social driver of online review generation—doctors' presence on online health platforms, which results in the reviewers (i.e., patients) and the reviewees (i.e., doctors) coexisting in the same medium. Drawing on the Stimulus‐Organism‐Response theory as an overarching framework, we advance hypotheses about the impact of doctors' presence on their patients' review behaviors, including review volume, review effort, and emotional expression. To achieve causal identification, we conduct a quasi‐experiment on a large online health platform and employ propensity score matching and difference‐in‐difference estimation. Our findings show that doctors' presence increases their patients' review volume. Furthermore, doctors' presence motivates their patients to exert greater effort and express more positive emotions in the review text. The results also show that the presence of doctors with higher professional titles has a stronger effect on review volume than the presence of doctors with lower professional titles. Our findings offer important implications both for research and practice.
Heritability of abnormalities in limbic networks of autism spectrum disorder children: Evidence from an autism spectrum disorder twin study
Authors: Fu Linyan , Li Chunyan , Li Yun , Cheng Xin , Cui Xiwen , Jiang Jiying , Ding Ning , Fang Hui , Tang Tianyu , Ke Xiaoyan
Published: February 2022

Although the limbic system is closely related to emotion and social behaviors, little is known about the integrity of limbic pathways and how genetics influence the anatomical abnormalities of limbic networks in children with autism spectrum disorder (ASD). Therefore, we used an ASD twin study design to evaluate the microstructural integrity and autism‐related differences in limbic pathways of young children with ASD and to estimate the heritability of limbic tracts microstructure variance. We obtained diffusion tensor imaging scans from 33 pairs of twins with ASD aged 2–9 years and 20 age‐matched typically developing children. The ACE model was used to estimate the relative effects of additive genetic factors (A), shared environmental factors (C) and specific environmental factors (E) on the variability of diffusivity measurements. We found a significant decrease in fractional anisotropy (FA) in the bilateral fornix and uncinate fasciculus (UF), as well as increased mean diffusivity (MD) and radial diffusivity (RD) in the bilateral fornix and right UF of ASD children. Correlation analysis showed that FA, MD, and lateralization indices of UF were correlated with autism diagnostic observation schedule scores. The ACE model revealed that genetic effects may drive some of the variability of microstructure in the bilateral fornix, cingulum, and left UF. In conclusion, in children with ASD, there are abnormalities in the white matter microstructure of the limbic system, which is related to the core symptoms; these abnormalities may be related to the relative contribution of genetic and environmental effects on specific tracts.

Lay Summary

Autism spectrum disorder (ASD) children have abnormal white matter structure in limbic system related to ASD symptoms, and genetic factors play an important role in the development of limbic tracts.
Passively immobilized cyanobacteria Nostoc species BB 92.2 in a moving bed photobioreactor (MBPBR): Design, cultivation, and characterization
Authors: Walther Jakob , Erdmann Niklas , Stoffel Michael , Wastian Katharina , Schwarz Anna , Strieth Dorina , Muffler Kai , Ulber Roland
Published: February 2022

The cyanobacterium Nostoc sp. BB 92.3. had shown antibacterial activity. A cultivation as biofilm, a self‐forming matrix of cells and extracellular polymeric substances, increased the antibacterial effect. A new photobioreactor system was developed that allows a surface‐associated cultivation of Nostoc sp. as biofilm. High‐density polyethylene carriers operated as a moving bed were selected as surface for biomass immobilization. This system, well established in heterotrophic wastewater treatment, was for the first time used for phototrophic biofilms. The aim was a cultivation on a large scale without inhibiting growth while maximizing immobilization. Cultivation in a small photobioreactor (1.5 L) with different volumetric filling degrees of carriers (13.4%–53.8%) in a batch process achieved immobilization rates of 70%–85% and growth was similar to a no‐carrier‐control. In a larger photobioreactor (65 L) essentially all of the biomass was immobilized on the carriers and the space‐time yield of biomass (0.018 gcell dry weight L−1 day−​​​​​​​1) was competitive compared to phototrophic biofilm cultivations from literature. The use of carriers increased the gas exchange in the reactor by a factor of 2.5–3 but doubled the mixing time. Enriched gassing with carbon dioxide resulted in a short‐term increase in growth rate, but unexpectedly it also adversely changed the growth morphology.
A Quality by Design and green LC technique for the determination of mast cell stabilizer and histamine receptor antagonist (Olopatadine HCl) in multiple formulations
Authors: Kowtharapu Leela Prasad , Katari Naresh Kumar , Ch. Surekha , Sandoval Christian A. , Muchakayala Siva Krishna , Konduru Naresh
Published: February 2022

Mast cell stabilizer and histamine receptor antagonist olopatadine hydrochloride (OPT) assay method predicated on LC have been established for the analysis in multiple formulations. The current method dealt with ophthalmic solution, nasal spray, and tablet formulation products. The isocratic chromatography method was optimized and validated with a Boston green C8 column (150 × 4.6 mm, 5 μm i.d.). Sodium dihydrogen phosphate buffer (pH 3.5) with acetonitrile in the ratio of 75:25 (v/v) was used as a mobile phase at a flow rate of 1.0 mL min−1 and at the column temperature of 30°C, and the detection was done at 299 nm. The method was validated as per International Council for Harmonisation (ICH) guidelines and United States Pharmacopoeia (USP). The accuracy results ranged from 99.9 to 100.7%, % relative standard deviation (RSD) from the precision was 0.5, and correlation coefficient from the linearity experiment was > 0.999. Solution stability was established for 24 h at room temperature and refrigerator conditions, and it was found that the solutions were stable. Using quality by design‐based experiment designs, critical quality attributes were studied and it was found that the method was robust. In all the forced degradation studies peak purity was passed, and no interference was found at the retention time of the active component. The method validation data demonstrated that the developed method is linear, precise, accurate, specific, robust, and stable for the determination of OPT from multiple formulations. Analytical eco‐scale tool, Green Analytical Procedure Index (GAPI) tool, and the National Environmental Method Index (NEMI) were used to evaluate the greenness of the method, and the analytical eco‐score of 77 for the presented method was found to be excellent.
Circular economy business models as resilient complex adaptive systems
Authors: De Angelis Roberta
Published: February 2022

Broad consensus seems to have emerged on the circular economy as a plausible and desirable solution to build prosperity while respecting ecological boundaries. However, its implementation in industry is slow paced. Whilst the systemic nature of the innovation required and barriers to implementation in complex sustainability transitions partially explain why this is the case, reflecting on the contribution of the growing scholarly literature on circular business models to orient management practice is also relevant. In fact, despite the existence of a fairly voluminous scholarly literature on the subject, practitioners are either uncertain or struggling about how to implement circular economy strategies and models. Using an integrative research approach to theory building and drawing on systems theory, this article proposes a resilient complex adaptive system view of circular business models. The resulting framework is a stepping‐stone to overcoming conceptual ambiguities and construct fallacies in the way circular business models are typified.
Biomarkers expression among paired serous ovarian cancer primary lesions and their peritoneal cavity metastases in treatment‐naïve patients: A single‐center study
Authors: Nikas Ilias P. , Lee Cheol , Song Min Ji , Kim Bohyun , Ryu Han Suk
Published: February 2022

Background

High‐grade serous ovarian carcinoma (HGSOC), the most common histologic subtype of ovarian epithelial cancer, is associated with treatment resistance, enhanced recurrence rates, and poor prognosis. HGSOCs often metastasize to the peritoneal cavity, while fluid cytology examination could identify such metastases. This retrospective study aimed to identify potential biomarker discrepancies between paired HGSOC primary tissues and metastatic peritoneal fluid cytology samples, processed as cell blocks (CBs).

Methods

Twenty‐four pairs of formalin‐fixed, paraffin‐embedded primary tissues and metastatic CBs from an equal number of treatment‐naïve patients were used, and immunohistochemistry (IHC) for epidermal growth factor receptor (EGFR), human epidermal growth factor receptor, programmed cell death‐1 ligand 1 (PD‐L1), and CD147 was applied.

Results

13/24 pairs showed discordant EGFR IHC results; in all these 13 patients, EGFR was positive (≥1+ membranous staining intensity found in at least 10% of the cancer cells) in the peritoneal, yet negative in the primary tissue samples. Notably, EGFR IHC was positive in 15/24 of the metastatic, whereas in just 2/24 of the primary HGSOC samples (p < 0.001). Although most PD‐L1 results were concordant, 5/24 and 6/24 pairs exhibited discordant results when stained with the E1L3N and 22C3 clones, respectively. Lastly, CD147 overexpression was found more often in the metastatic rather than the matched primary HGSOCs stained with CD147, though the difference was not significant.

Conclusions

Cytology from effusions could be considered for biomarker testing when present, even when tissue from the primary cancer is also available and adequately cellular, as it could provide additional information of potential clinical significance.
Selective Alkyne Semi‐Hydrogenation by PdCu Nanoparticles Immobilized on Stereocomplexed Poly(lactic acid)
Authors: Oberhauser Werner , Frediani Marco , Mohammadi Dehcheshmeh Iman , Evangelisti Claudio , Poggini Lorenzo , Capozzoli Laura , Najafi Moghadam Peyman
Published: February 2022

Polymer‐supported PdCu alloy nanoparticles with a palladium to copper atom ratio of 1 have been synthesized upon: (i) Coordination of palladium/copper acetate to 2,2’‐bipyridine‐end functionalized poly(lactic acid) (PLA); (ii) Stereocomplexation of PLA‐based macrocomplexes of opposite stereochemistry, and (iii) metal reduction with hydrogen. The obtained supported PdCu nanoparticles were successfully applied in the semi‐hydrogenation of industrially important alkynols, such as 3‐hexyn‐1‐ol and 2‐butyne‐1,4‐diol leading to the corresponding cis‐alkenol in high selectivity (98 %) under mild reaction conditions (i. e. ethanol, T (25 °C), p(H2)=3 bar) in the absence of any further additive. From a comparison of the catalytic performance of supported PdCu nanoparticles with those of Pd and Cu, located in the same chemical environment, emerged a clear alloy effect (i. e. high chemoselectivity for the alkene at high alkyne conversion). Recycling experiments conducted with the PdCu‐based catalyst proved the stability of the catalyst with time, even by its recovering in air atmosphere.
Impact of Intermolecular Non‐Covalent Interactions in a CuI8PdII1 Discrete Assembly: Conformers’ Geometries and Stimuli‐Sensitive Luminescence Properties
Authors: Moutier Florent , Schiller Jana , Lecourt Constance , Khalil Ali Moustafa , Delmas Vincent , Calvez Guillaume , Costuas Karine , Lescop Christophe
Published: February 2022

A new highly solid‐state luminescent phase of a previously reported weakly luminescent CuI8PdII1 dicationic assembly is reported revealing the high geometrical versatility of this moiety that importantly alters its luminescent properties. This very minor new species Bc is based on a different conformer scaffold than the one encountered in the previously reported Bo form and, essentially differs from Bo by displaying shorter CuI‐CuI intermetallic distances. DFT calculations allow concluding that the predominance in the solid‐state of the weakly luminescent and less stable Bo phase is due to the extra stability induced by a larger number of intermolecular non‐covalent π‐CH interactions in its crystalline packing and not by the intrinsic stability of the CuI8PdII1 dicationic moiety. Calculations also revealed that a more stable conformation Bcalc is expected in vacuum, which bears a different distribution of CuI‐CuI intermetallic distances than the dications in Bo and Bc phases. Taking into account that the geometrical alterations are associated to drastic changes of luminescence properties, this confer to the CuI8PdII1 assembly high potentiality as stimuli‐sensitive luminescent materials. Indeed, by applying mechanical or thermal stress to samples of Bo phase, new phases Bg and Bm, respectively, were obtained. Alterations of the solid‐state photophysical properties of these new species compared to those recorded for Bo are reported together with a combined experimental and computed study of the structures/properties relationships observed in these phases.
A Fully Conjugated Porphyrin‐[36]Octaphyrin‐Porphyrin Hybrid Tape Exhibiting Möbius Aromaticity
Authors: Nakai Akito , Tanaka Takayuki , Osuka Atsuhiro
Published: February 2022

Directly meso‐meso linked porphyrin‐tetrabromo[36]octaphyrin‐porphyrin hybrid trimer 10 was successfully synthesized via acid‐catalyzed condensation reaction and subsequent oxidation. ZnII‐metalation of 10 induced transannular meso‐meso bond formation to give Möbius aromatic bis‐ZnII octaphyrin 11, which was oxidized by DDQ/Sc(OTf)3 to provide fully conjugated porphyrin‐[36]octaphyrin‐porphyrin hybrid tape 12 as the first example of porphyrin tape exhibiting Möbius aromaticity. Hybrid tape 12 displays significantly red‐shifted absorption and small electrochemical HOMO‐LUMO gap, indicating the effective conjugation through the whole chromophores.
Controlling Tautomerization in Pyridine‐Fused Phosphorus‐Nitrogen Heterocycles
Authors: McNeill J. Nolan , Karas Lucas J. , Bard Jeremy P. , Fabrizio Kevin , Zakharov Lev N. , MacMillan Samantha N. , Brozek Carl K. , Wu Judy I. , Johnson Darren W. , Haley Michael M.
Published: February 2022

Inclusion of a second nitrogen atom in the aromatic core of phosphorus‐nitrogen (PN) heterocycles results in unexpected tautomerization to a nonaromatic form. This tautomerization, initially observed in the solid state through X‐ray crystallography, is also explained by computational analysis. We prepared an electron deficient analogue (2 e) with a fluorine on the pyridine ring and showed that the weakly basic pyridine resisted tautomerization, providing key insights to why the transformation occurs. To study the difference in solution vs. solid‐state heterocycles, alkylated analogues that lock in the quinoidal tautomer were synthesized and their different 1H NMR and UV/Vis spectra studied. Ultimately, we determined that all heterocycles are the aromatic tautomer in solution and all but 2 e switch to the quinoidal tautomer in the solid state. Better understanding of this transformation and under what circumstances it occurs suggest future use in a switchable on/off hydrogen‐bond‐directed receptor that can be tuned for complementary hydrogen bonding.
The broken record: How the music industry is making sense of uncertainty and change
Authors: Green Todd , Sinclair Gary
Published: February 2022

As the recording music industry entered the digital era, significant turmoil emerged due to piracy and illegal downloading, and royalty payments to artists via streaming platforms. To date, the previous research examining the industry shift focused on consumer‐based decisions such as whether to download music illegally, and, more recently, experiences with streaming services. Using sensemaking as our lens, we examine changes and challenges through in‐depth interviews with music industry practitioners. The participants have been directly impacted by the digital shift in general and by specific issues such as piracy and poor compensation from streaming platforms. We develop a typology of industry members based on their development of sensemaking capabilities as they navigate the ever‐changing industry and the resulting influence on market practices.
Data characteristics aware prediction model for power consumption of data center servers
Authors: Shen Ziyu , Zhou Qing , Zhang Xusheng , Xia Bin , Liu Zheng , Li Yun
Published: February 2022

Due to the rapid increase in the number and scale of data centers, the information and communication technology (ICT) equipment in data centers consumes an enormous amount of power. A power prediction model is therefore essential for decision‐making optimization and power management of ICT equipment. However, it is difficult to predict the power consumption of data centers accurately due to the complex power patterns and nonlinear interdependencies among components. Existing methods either rely on standard formulas, or simply treat it as time series, both leading to poor power prediction accuracy. To overcome those limitations, in this article, we present a systematic power prediction framework called characteristic aware attention‐augmented deep learning‐based prediction method. In particular, we first analyze the different power consumption series to illustrate their different temporal characteristics. Second, we perform different data processing for the corresponding characteristics of power series samples. Third, we propose an accurate and efficient neural network model to predict future power consumption with the pretreated data. The experimental results show that the proposed model is able to achieve superior prediction accuracy.
Combining Open‐Shell Verdazyl Environment and Co(II) Spin‐Crossover: Spinmerism in Cobalt Oxoverdazyl Compound
Authors: Roseiro Pablo , Ben Amor Nadia , Robert Vincent
Published: February 2022

The spin states of a Co(II) oxoverdazyl compound are investigated by means of wavefunction‐based calculations. Within a ca. 233 K energy window, the ground state and excited states display a structure‐sensitive admixture of low‐spin SM=1/2 in a dominant high‐spin SM=3/2 Co(II) ion as indicated by the localized molecular orbitals. The puzzling spin zoology that results from the coupling between open‐shell radical ligands and a spin‐crossover metal ion gives rise to this unusual scenario, which extends the views in molecular magnetism. In agreement with experimental observation, the low‐energy spectroscopy is very sensitive to deformations of the coordination sphere, and a growing admixture of Co(II) low‐spin is evidenced from the calculations. In analogy with mesomerism that accounts for charge delocalization, entanglement combines different local spin states to generate a given total spin multiplicity, a spinmerism phenomenon.
Diabetic ketoacidosis amongst patients with COVID‐19: A retrospective chart review of 220 patients in Pakistan
Authors: Muhammad Asim , Hakim Muhammad , Afaq Saima , Khattak Farhad Ali , Shakireen Najmush , Jawad Muhammad , Saeed Rabia , Haq Zia Ul
Published: February 2022

Objectives

To determine the frequency of diabetes mellitus and diabetic ketoacidosis and associated factors in COVID‐19‐positive patients.

Background

High mortality amongst SARS‐Cov2 patients may be attributed to diabetes and diabetic ketoacidosis.

Methods

A total of 220 COVID‐19 positive patients, hospitalized in North West General Hospital & Research Center, Peshawar, KP, Pakistan, from April to September 2020, were analysed using STATA 14. Patients with positive PCR were labelled as COVID‐19 positive and were included in the study. Patients with a clinical picture of COVID‐19 and negative PCR were excluded from the study. Those having ketonemia >0.6 and random blood glucose level >250mg/dl, while HCO3 (bicarbonate) ≤18, were labelled as diabetic ketoacidosis. The statistical significance level was set at p < .05.

Results

A total of 220 COVID‐19 patients were admitted; 166 (75.4%) were male and 54 (24.5%) were female. The mean age in years of the patients was 55.95 (SD13.9). About 57.7% of patients had diabetes mellitus, and 15 (6.8%) patients developed diabetic ketoacidosis. Amongst those with DKA, 5 patients died during hospital admission. The use of steroids was significantly higher (p < .001) in the DKA group compared with non‐DKA patients. Hypertension (103,46.8%) and fever (170,77.3%) were the most reported comorbidity and symptom respectively.

Conclusion

The proportion of diabetes mellitus is high in patients with COVID‐19. Diabetic ketoacidosis is a frequent complication in this group associated with in‐hospital mortality. Steroid administration for COVID‐19 should be balanced with strict glycemic control to prevent diabetic ketoacidosis and increase hospital survival.
Eating disorder onset during childhood is associated with higher trauma dose, provisional PTSD, and severity of illness in residential treatment
Authors: Brewerton Timothy D. , Gavidia Ismael , Suro Giulia , Perlman Molly M.
Published: February 2022

Objective

Age of eating disorder (ED) onset has been of significant interest to both researchers and clinicians. The identification of factors associated with early or child onset has important prevention and treatment implications. The presence of prior trauma, resultant posttraumatic stress disorder (PTSD), ED severity, and comorbid psychopathology are of particular relevance to age of ED onset, but data are limited.

Methods

Adults (≥18 years, 93% female, total n = 1283) admitted to residential ED treatment self‐reported age of ED onset. Patients were divided into child onset (ages 5–10 years), adolescent onset (11–17 years), and adult onset (≥18 years) groups and compared on a number of clinical features and assessment measures.

Results

The child onset group had significantly higher rates and doses of traumatic life events; higher current PTSD prevalence; higher BMIs, higher severity of ED, depression and state‐trait anxiety symptoms; worse quality of life; and more prior inpatient and residential admissions for ED treatment, in comparison to both the adolescent and adult onset groups. Similarly, the adolescent onset group had significantly higher rates than the adult onset group.

Conclusions

These results have important implications for prevention, treatment and long‐term follow‐up and highlight the need for early trauma‐focussed treatment of ED patients.
Comparison of Exposure Techniques and Vitality Assessment of Mosses in Active Biomonitoring for Their Suitability in Assessing Heavy Metal Pollution in Atmospheric Aerosol
Authors: Świsłowski Paweł , Nowak Arkadiusz , Rajfur Małgorzata
Published: February 2022

The most widespread and used technique is the moss-bag method in active biomonitoring of air pollution using mosses. In the literature, we can find various studies on the standardization of this method, including attempts to standardize treatments and preparation procedures for their universal application. Few works comprehensively focus on other methods or compare other techniques used in active biomonitoring with mosses, especially including measurements of their vital parameters. Our experiment aimed to assess air pollution by selected heavy metals (Cu, Zn, Cd, Pb, Mn, Fe, and Hg) using three moss species (Pleurozium schreberi, Sphagnum fallax, and Dicranum polysetum) during a 12-week exposure in an urban area. Mosses were exposed simultaneously using four techniques: moss bag in three variants (exposed to air for total deposition of heavy metals, exposed to air for only dry deposition, and sheltered from the wind) and transplants in boxes. Increases in heavy metal concentrations in mosses were determined using the relative accumulation factor (RAF). The actual quantum yield of photosystem II photochemical was also analyzed as the main vitality parameter. The results indicate that all moss species during the changing environmental conditions survived and retained their vitality, although it decreased by >50% during the exposure. The best biomonitor was the moss P. schreberi, whose RAF increments were the highest throughout the study period for the majority of elements. The moss-bag technique had a statistically significant effect (almost 40%) on the concentration value of a given metal for a certain species, and thus it is the most recommended technique that can be applied in air quality monitoring in urban areas. Environ Toxicol Chem 2022;41:1429–1438. © 2022 SETAC
What are the characteristics of the cases we use to teach and learn evaluation?
Authors: Kallemeyn Leanne M. , Titiml Eleanor N. , Galib Linda , Castelin Kim , Montrosse‐Moorhead Bianca , Ensminger David C. , Linfield Kenneth J.
Published: February 2022

Case‐centered teaching and learning is important for illustrating evaluation approaches, practicing professional problem‐solving and ethical decision‐making, and teaching professional skills and competencies. In this study we provide findings on a content analysis of 148 written cases used to teach evaluation and a critical analysis of five purposively selected cases. The findings demonstrate that evaluators have written many cases to teach the situational nature of evaluation practice. Most of the cases are simulations of practice, which include how the case actors’ think, decide, and act in an evaluation context. The study findings point to several areas for strengthening case‐centered teaching in evaluation, including providing clear learning objectives, developing supporting resources for instructors, aligning cases with professional competencies and/or core concepts in the field, developing cases to promote active and problem‐based learning, ensuring cases represent equity‐informed practices, and broadening the representation of diverse people and contexts.
How do we teach and learn with cases?
Authors: Montrosse‐Moorhead Bianca , Ensminger David C , Roseveare Christine
Published: February 2022

In this article, we review the literature on learning and teaching with cases drawing from several applied professions (e.g., education, business, medicine). First, we summarize the learning philosophies and concepts that ground case‐centered teaching and learning. This section touches on views of professional practice, important and relevant theories and concepts, and the value of decomposition of professional practice. Then, we use the idea of decomposition of professional practice to illuminate for readers how the learning philosophies and concepts that ground case‐centered teaching might show up in evaluation classrooms. This discussion necessarily focuses on instructional design, types of cases, issues to consider in selecting cases, developing meaningful questions, and cultivating the type of learning environment case‐centered teaching and learning demands. Implications for evaluation educators and research on evaluation are noted.
How do we deepen our story reservoir by designing, developing, and writing instructional cases for teaching evaluation?
Authors: Ensminger David C. , Frazier Elissa W. , Montrosse‐Moorhead Bianca , Linfield Kenneth J.
Published: February 2022

Practicing evaluators' professional stories can serve as rich resources for training novice evaluators. However, converting professional stories into a written teaching case requires more than simply writing down a narrative. This article discusses the components of well written cases present in the literature, and provides guidance on how to design, develop, and write four types of cases using instructional design principles that address aspects of pedagogical knowledge and pedagogical content knowledge. Additionally, this article discusses the development of instructor resources that can accompany a case narrative and support the use of the case as an instructional tool.
Harnessing anti‐tumor and tumor‐tropism functions of macrophages via nanotechnology for tumor immunotherapy
Authors: Zheng Yanhui , Han Yaobao , Sun Qiao , Li Zhen
Published: February 2022

Reprogramming the immunosuppressive tumor microenvironment by modulating macrophages holds great promise in tumor immunotherapy. As a class of professional phagocytes and antigen‐presenting cells in the innate immune system, macrophages can not only directly engulf and clear tumor cells, but also play roles in presenting tumor‐specific antigen to initiate adaptive immunity. However, the tumor‐associated macrophages (TAMs) usually display tumor‐supportive M2 phenotype rather than anti‐tumor M1 phenotype. They can support tumor cells to escape immunological surveillance, aggravate tumor progression, and impede tumor‐specific T cell immunity. Although many TAMs‐modulating agents have shown great success in therapy of multiple tumors, they face enormous challenges including poor tumor accumulation and off‐target side effects. An alternative solution is the use of advanced nanostructures, which not only can deliver TAMs‐modulating agents to augment therapeutic efficacy, but also can directly serve as modulators of TAMs. Another important strategy is the exploitation of macrophages and macrophage‐derived components as tumor‐targeting delivery vehicles. Herein, we summarize the recent advances in targeting and engineering macrophages for tumor immunotherapy, including (1) direct and indirect effects of macrophages on the augmentation of immunotherapy and (2) strategies for engineering macrophage‐based drug carriers. The existing perspectives and challenges of macrophage‐based tumor immunotherapies are also highlighted.
Identification of novel compounds in rose absolute with gas chromatography/high‐resolution mass spectrometry
Authors: Remy Pierre‐Alain , Sarrazin Elise , Pérès Christophe , Dugay José , David Nathalie , Vial Jérôme
Published: February 2022

Gas Chromatography/High‐Resolution Mass Spectrometry (HRMS) was used to identify new compounds in Rosa damascena and Rosa centifolia absolutes. These compounds were esters derived from the main alcohols of rose absolute (phenylethyl alcohol, geraniol, citronellol, nerol, and (E,E)‐farnesol). Based on low‐resolution mass spectrometry (LRMS) and HRMS data of rose absolutes, hypotheses were first formulated. In a second stage, the standards of these candidate structures were synthetized and analyzed by LRMS using apolar and polar columns. LRMS spectra of these standards, and apolar and polar retention indices (RI) were compared with those of candidate structures. Only four out of nineteen molecules were validated by these three criteria mostly due to an important difference of polar RIs between the standards and the compounds detected in rose absolutes. In a third stage, absolutes were spiked with synthesized standards and were analyzed by HRMS on both apolar and polar columns to confirm the presence of these candidate structures. Finally, 19 new compounds were identified in Rosa damascena and Rosa centifolia absolutes.
Reforming the provision of cross‐border medical care: Evidence from Spain
Authors: Amuedo‐Dorantes Catalina , Rivera‐Garrido Noelia , Vall Castelló Judit
Published: February 2022

Cross‐border medical care, defined as care facilitated by a local health provider under pre‐established regional agreements, as in the case of European Union (EU) citizens accessing care within EU countries, has been on the rise. Unlike medical tourism, typically sought by patients through their own volition and paid for out‐of‐pocket, cross‐border medical care is often reimbursable or paid for directly by the responsible government. Yet, because nations vary in the extent of health coverage offered to their residents, these expenditures are often only partially reimbursed. The resulting financial burden for some countries can be large and not reciprocal, straining regional and country‐level finances. We analyze the effectiveness of a legislative measure adopted by a Spanish region in January 2012 with the purpose of curbing cross‐border medical care. Using a comprehensive administrative dataset of all medical procedures performed in the country between 2008 and 2015, we find that the measure led to a drastic drop in the number of foreigners' hospitalizations and a reduction of 4.8 million euros/trimester in costs. Finally, the decrease in hospitalizations did not disproportionally affect patients based on their gender, age, or origin, although it fostered a reduction in readmissions.
PET/CTversus triple endoscopy in initial workup ofHPV+ oropharyngeal squamous cell carcinoma
Authors: Muller Richard Grant , Weidenbecher Mark , Ludlow David
Published: February 2022

Background

Synchronous primary tumors (SPTs) are detected via triple endoscopy or positron emission tomography/computed tomography (PET/CT). Patients with human papillomavirus‐associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) lack risk factors for SPTs.

Methods

We performed a single institution retrospective review of the efficacy of triple endoscopy and PET/CT in HPV+ OPSCC patients.

Results

Sixty‐five HPV+ OPSCC patients underwent triple endoscopy and PET/CT. Patients were white (n = 48, 72.7%), male (n = 53, 81.5%), mean 58.7 ± 8.1 years old. SPT was detected in 1 (1.5%) patient via PET/CT. No SPTs were detected on triple endoscopy. PET/CT had 100% and 95.3% sensitivity and specificity, respectively. PET/CT positive predictive value (PPV) and negative predictive value (NPV) were 25.0% and 100%, respectively. Triple endoscopy specificity and NPV was 90.2% and 93.2%, respectively.

Conclusions

PET/CT is superior to triple endoscopy in ruling out SPTs. With negative PET/CT, only direct laryngoscopy with biopsy may be necessary.
A nomogram based on tumor response to induction chemotherapy may predict survival in locoregionally advanced nasopharyngeal carcinoma
Authors: Jiang Yu‐Ting , Chen Kai‐Hua , Liang Zhong‐Guo , Yang Jie , Wei Si‐Qi , Qu Song , Li Ling , Zhu Xiao‐Dong
Published: February 2022

Background

To evaluate the clinical significance of tumor response to induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients and further to develop a nomogram for predicting survival prognosis.

Methods

A total of 498 patients with stage III‐IVA NPC applying IC and concurrent chemotherapy were reviewed (training cohort, n = 376; validation cohort, n = 122).

Results

Tumor response was an independent predictor for clinical outcomes. The nomogram included age, N stage, pretreatment Epstein–Barr virus DNA, lymphocyte‐to‐monocyte ratio, and tumor response achieved an ideal C‐index of 0.703 (95% CI 0.655–0.751) in the validation cohort for predicting overall survival (OS), which outperformed than that of the TNM system alone (C‐index, 0.670, 95% CI: 0.622–0.718). In addition, the nomogram could successfully classified patients into different risk groups.

Conclusions

We established and validated a precise and convenient nomogram based on tumor response for predicting the OS of LANPC patients.
Prognostic factors of children and adolescents with T‐cell acute lymphoblastic leukemia after allogeneic transplantation
Authors: Ishida Hisashi , Kato Motohiro , Kawahara Yuta , Ishimaru Sae , Najima Yuho , Kako Shinichi , Sato Maho , Hiwatari Mitsuteru , Noguchi Maiko , Kato Keisuke , Koh Katsuyoshi , Okada Keiko , Iwasaki Fuminori , Kobayashi Ryoji , Igarashi Shunji , Saito Shoji , Takahashi Yoshiyuki , Sato Atsushi , Tanaka Junji , Hashii Yoshiko , Atsuta Yoshiko , Sakaguchi Hirotoshi , Imamura Toshihiko
Published: February 2022

Acute lymphoblastic leukemia (ALL) is the most common cancer during childhood, and some high‐risk patients with ALL require hematopoietic stem cell transplantation (HSCT). Mainly due to small patient numbers, studies focusing specifically on children and adolescents with T‐cell ALL (T‐ALL) are limited. Using a nationwide registry, we retrospectively analyzed data from patients under 20 years old who underwent their first HSCT for T‐ALL between 2000 and 2018. As a result, total 484 patients were included, and their median follow‐up period was 6.9 years after HSCT for survivors. While patients receiving HSCT at first complete remission (CR) showed relatively good 5‐year leukemia free survival (5yLFS, 73.5%), once relapse occurred, their prognosis was much worse (44.4%) even if they attained second remission again (p < 0.001). Among patients receiving HSCT at CR1, grade II–IV acute graft versus host disease was associated with worse overall and LFS than grade 0–I (5yLFS 69.5% vs. 82.1%, p = 0.026) mainly due to high non‐relapse mortality. Among those patients, patients receiving related bone marrow transplantation, unrelated bone marrow transplantation, or unrelated cord blood transplantation showed similar survival (5yLFS, 73.2%, 76.3%, and 77.0%, respectively). For patients undergoing cord blood transplantation at CR1, total‐body irradiation‐based myeloablative conditioning was associated with better 5yLFS than other conditioning regimens (85.4% vs. 62.2%, p = 0.044), as it reduced the risk of relapse. These results indicate that relapsed patients have much less chance of cure, and that identifying patients who require HSCT for cure and offering them HSCT with optimal settings during CR1 are crucial for children and adolescents with T‐ALL.
Use of BTK inhibitors with special focus on ibrutinib in Waldenström macroglobulinemia: An expert panel opinion statement
Authors: Ferrero S. , Gentile Massimo , Laurenti Luca , Mauro Francesca Romana , Martelli Maurizio , Sportoletti Paolo , Visco Carlo , Zinzani Pier Luigi , Tedeschi Alessandra , Varettoni M.
Published: February 2022

The pivotal role that ibrutinib plays in the management of Waldenström macroglobulinemia (WM) is undisputed but there are ongoing questions regarding its positioning in the therapeutic algorithm of WM as well as in some peculiar clinical situations. A panel of experts from Italy was convened to provide real world recommendations on the use of BTK inhibitors in lymphoproliferative diseases in general, and in patients with WM in particular. This position paper represents the panel's collective analysis, evaluation, and opinions and is made up of a series of questions frequently asked by practicing clinicians and answers based on currently available evidence.
Determinants of cervical cancer screening uptake among women with access to free screening: A community‐based study in peri‐urban Ghana
Authors: Tawiah Augustine , Konney Thomas O. , Dassah Edward T. , Visser Lucia E. , Amo‐Antwi Kwabena , Appiah‐Kubi Adu , Bell Sarah G. , Johnston Carolyn , Lawrence Emma R.
Published: February 2022

Objective

Cervical cancer can be prevented by regular screening; however, screening rates are low in developing countries. We evaluated the proportion of women screened, modalities of screening utilized, and factors influencing uptake among Ghanaian women with access to free screening services.

Methods

Participants were women aged 25–65 in Asokore‐Mampong, Ghana. A structured questionnaire collected socio‐demographic characteristics, risk factors, knowledge of, and utilization of cervical cancer screening. Adjusted logistic regression evaluated predictors of screening.

Results

Of 710 participants, the majority had heard of cervical cancer (64.6%) and screening (57.7%). Screening utilization was 24.6%. Visual inspection with acetic acid was the most common screening method (97.1%). For those who had never been screened, common reasons were believing they were healthy (21.7%), fearing pain (12.9%), lacking awareness of screening (11.8%), and being too busy (11.6%). Participants who were aged 35–44 (aOR 1.82; 95% CI 1.09–3.03; p = 0.023), married (aOR 3.98; 95% CI 1.68–9.40; p = 0.002), formally employed (aOR 9.31; 95% CI 2.86–30.35; p <0.001), and had higher cervical cancer knowledge (aOR 3.98; 95% CI 2.64–6.02; p <0.001) were more likely to have been screened.

Conclusion

Despite geographic proximity to a health center that provides free cervical cancer screening, screening uptake among Ghanaian women remains low.
Outcomes of subchorionic hematoma‐affected pregnancies in the infertile population
Authors: Inman Erin R. , Miranian Daniel C. , Stevenson Micaela J. , Kobernik Emily K. , Moravek Molly B. , Schon Samantha B.
Published: February 2022

Objective

To determine the implications of an incidentally noted subchorionic hematoma on pregnancy outcomes in the infertile population.

Methods

Retrospective cohort study at a tertiary care, university‐based facility. All patients with intrauterine pregnancy on initial obstetric ultrasound presenting to an infertility clinic between January 2015 and March 2018 (n = 1210), regardless of treatment cycle, were included. Nonviable pregnancies were excluded. The main outcome measured was association between subchorionic hematoma and first trimester miscarriage.

Results

The prevalence of subchorionic hematoma was 12.5% (n = 151) and did not differ by type of fertility treatment. There was no association between subchorionic hematoma and first trimester miscarriage; however, among patients with subchorionic hematoma, those who reported both bleeding and cramping had an increased probability of miscarriage compared to those without symptoms (0.62 vs. 0.12, P <0.001). The live birth rate in this sample was 81.3% and there were no statistically significant differences in pregnancy outcomes between those with and without subchorionic hematoma.

Conclusion

Among an infertile population, there was no increased risk of miscarriage when subchorionic hematoma was seen on early ultrasound; however, when patients noted both vaginal bleeding and cramping, their probability of miscarriage was significantly increased.
On intriguing sets in five classes of strongly regular graphs
Authors: Sun Xiufang , Lu Jianbing
Published: February 2022

In this paper, we construct intriguing sets in five classes of strongly regular graphs defined on nonisotropic points of finite classical polar spaces, and determine their intersection numbers.
Hsa_circ_0041268 promotes NSCLC progress by sponging miR‐214‐5p/ROCK1
Authors: Yang Wenhui , Wu Lina , Jin Mingming
Published: February 2022

Circular RNAs hold significant regulatory functions during various tumors. However, the exact hsa_circ_0041268 roles in non‐small cell lung cancer (NSCLC) along with regulatory mechanism are unknown. In this study, RT‐qPCR was used to perceive hsa_circ_0041268 expressions in NSCLC cell lines. Our team constructed small interfering RNA for hsa_circ_0041268. NSCLC cell proliferation, migration, and tumorigenesis in nude mice were assayed to confirm hsa_circ_0041268 activities in NSCLC cells. We then used bioinformatics and luciferase reporter analyses to characterize the hsa_circ_0041268 downstream targets. The result shows that the expressions of hsa_circ_0041268 incremented in NSCLC cell lines and hsa_circ_0041268 downregulation decreased cell proliferation and migration. ROCK1 and miR‐214‐5p were hsa_circ_0041268 downstream targets. miR‐214‐5p downregulation or ROCK1 overexpression restored migration and proliferation abilities after hsa_circ_0041268 silencing. ROCK1 overexpression renovated migration and proliferation abilities after miR‐214‐5p overexpression.In vivoinvestigations confirmed that hsa_circ_0041268 downregulation inhibited tumor formation and metastasis in nude mice xenografts. Together, results demonstrated that hsa_circ_0041268 acted as tumor promoter through novel hsa_circ_0041268/miR‐214‐5p/ROCK1 axis, which highlighted its potential as NSCLC therapeutic agent.
Expanded carrier screening in the United States: A systematic evidence review exploring client and provider experiences
Authors: Ramdaney Aarti , Lichten Lauren , Propst Lauren , Mann Caitlin , Lazarin Gabriel A. , Jones Malorie , Taylor Amy , Malinowski Jennifer
Published: February 2022

The aim of carrier screening is to identify prospective parents at risk of having a pregnancy affected with an autosomal recessive or X‐linked disorder. Though minimal guideline‐based screening is available, expanded carrier screening (ECS) is quickly becoming a feasible option for the general population due to its growing availability and affordability. However, the impact of ECS on clients and providers remains relatively unexplored. We performed a systematic evidence review to identify publications describing client‐, provider‐, and test‐related outcomes. We searched several biomedical databases for articles published between January 1, 2003 and May 31, 2021. Studies were eligible for inclusion if they described genetic counseling and/or genetic testing for carrier screening (minimal guideline‐based or ECS) in a prenatal or preconception setting in the United States. Title and abstract screening were performed using the Raayan web application or customized Google Forms. Full‐text review and data extraction of included articles were performed using custom Google Forms. Two researchers performed a multistep selection process independently for validation purposes. Of 5413 unique articles screened, 36 studies were included with several studies contributing to multiple outcomes. Twenty described outcomes relating to patients/clients, 10 described provider‐based outcomes, and 16 described test‐based outcomes. Findings suggest that client and provider perceptions of ECS and minimal guideline‐based carrier screening are multifaceted. Though clients have expressed desire for ECS, clinical uptake and impact on reproductive decision‐making varies. Additionally, though genetic counselors seem to be comfortable with ECS, most other reproductive care providers seem to prefer minimal guideline or ancestry‐based screening due to perceived barriers, such as time needed for ECS results disclosure and follow‐up, as well as the desire to have panels set by professional societies/recommendations. There are limitations within the gathered literature, leading to potential uncertainty in the generalizability of our review. We outline several recommendations for future studies, including the need to examine variant interpretation and use of next‐generation sequencing.