bluuebunny/crossref_metadata_2025 huggingface dataset:
Quaternary lacustrine dolostones of Sahara: New geoheritage evidence from the Farafra Oasis (Egypt)
Authors: Farouk Sherif , Ruban Dmitry A. , Al‐Khatany Khaled M.
Published: May 2021

Oases of the Western Desert of Egypt host numerous geoheritage features. Field investigations in the Farafra Oasis have permitted to establish the presence of brown dolostones occurring in channels incised in the Upper Cretaceous rocks, on slopes of topographic highs, as fills of the karst features, and directly on wide depressions floor. Their origin is linked to carbonate deposition in a palaeolake that existed in the pluvial conditions of the Pleistocene. Such dolostones are rare on regional, national, and even global scales, and, thus, they constitute a high‐value geoheritage feature. The latter can be assigned to sedimentary, palaeogeographical, and stratigraphical geoheritage types. The most typical locality of these lacustrine dolostones is North Ain El‐Wadi that is proposed as a geosite. This new evidence extends the previous knowledge of the geoheritage of the Farafra Oasis. Although the main utility of the proposed geosite is scientific, this object can also be used for the purposes of geoeducation and geotourism in combination with the other geoheritage resources of the central part of the Western Desert of Egypt.
Abnormal prediction error processing in schizophrenia and depression
Authors: Yaple Zachary Adam , Tolomeo Serenella , Yu Rongjun
Published: May 2021

To make adaptive decisions under uncertainty, individuals need to actively monitor the discrepancy between expected outcomes and actual outcomes, known as prediction errors. Reward‐based learning deficits have been shown in both depression and schizophrenia patients. For this study, we compiled studies that investigated prediction error processing in depression and schizophrenia patients and performed a series of meta‐analyses. In both groups, positive t‐maps of prediction error tend to yield striatum activity across studies. The analysis of negative t‐maps of prediction error revealed two large clusters within the right superior and inferior frontal lobes in schizophrenia and the medial prefrontal cortex and bilateral insula in depression. The concordant posterior cingulate activity was observed in both patient groups, more prominent in the depression group and absent in the healthy control group. These findings suggest a possible role in dopamine‐rich areas associated with the encoding of prediction errors in depression and schizophrenia.
Reliability of the 100 mL water swallow test in patients with head and neck cancer and healthy subjects
Authors: Vermaire Jorine A. , Terhaard Chris H. J. , Verdonck‐de Leeuw Irma M. , Raaijmakers Cornelis P. J. , Speksnijder Caroline M.
Published: May 2021

Background

Dysphagia may occur in up to 44% of patients with head and neck cancer (HNC) treated with radiation therapy and up to 84% of patients treated with surgery. To test the extent of dysphagia, the 100 mL water swallow test (WST) was developed. In this study, reliability of the 100 mL WST was determined in patients with HNC and healthy subjects.

Methods

Thirty‐three patients and 40 healthy subjects performed the WST twice on the same day. To assess reliability, the intraclass correlation coefficient (ICC2,1), standard error of measurement, smallest detectable change, and limits of agreement were calculated.

Results

Good to excellent correlations were found for patients with HNC (number of swallows; ICC = 0.923, duration; ICC = 0.893), and excellent correlations for healthy subjects (number of swallows; ICC = 0.950, duration; ICC = 0.916).

Conclusion

The 100 mL WST has a good to excellent reliability in patients with HNC and healthy subjects.
Nasal nitric oxide testing for allergic rhinitis patients: Systematic review and meta‐analysis
Authors: Wang Bingbing , Wu Zhenchao , Wang Feifei , Yin Zuojuan , Shi Lei , Liu Yi
Published: May 2021

Background

Nasal nitric oxide (nNO) levels in allergic rhinitis (AR), healthy people or nonallergic rhinitis (NAR) have shown contradicting results in previous studies. By meta‐analysis, we reviewed studies that measured nNO in AR patients to assess nNO's ability to discriminate AR from healthy people or NAR.

Methods

We systematically searched PubMed, Cochrane, Embase, Ovid, Web of Science, Wanfang Data, CNKI until December 15, 2020. Differences were expressed as standardized mean differences (SMD) with 95% confidence interval (CI), by random‐effects method.

Results

A total of 10 original studies with 561 AR patients, 327 healthy controls, 123 NAR patients were included in the narrative synthesis and 9 studies in the meta‐analysis. nNO in AR was significantly increased compared with healthy controls (SMD: 0.989; 95% CI: 0.402, 1.576; p = .001) or NAR (SMD: 0.680; 95% CI: 0.101, 1.259; p = 0.021). However, subgroup analysis based on measuring process and patient characteristics showed that no significant differences were detected in nNO between AR patients with nasal polyps or sinusitis or marked ostial obstruction and healthy controls.

Conclusions

nNO is a potential indicator for recognizing AR. Nasal polyps, sinusitis and marked ostial obstruction should be considered before nNO is applied to detect AR.
Validation of Oxford Cognitive Screen: Executive Function (OCS‐EF), a tablet‐based executive function assessment tool amongst adolescent females in rural South Africa
Authors: Rowe Kirsten , Duta Mihaela , Demeyere Nele , Wagner Ryan G. , Pettifor Audrey , Kahn Kathleen , Tollman Stephen , Scerif Gaia , Stein Alan
Published: May 2021

Short, reliable, easily administered executive function (EF) assessment tools are needed to measure EF in low‐ and middle‐income countries, particularly in sub‐Saharan Africa given the prevalence of human immunodeficiency virus (HIV)‐associated neurocognitive disorder. We administered Oxford Cognitive Screen—Executive Function (OCS‐EF) to 932 rural South African females (mean age 19.7 years). OCS‐EF includes seven tasks: two hot inhibition tasks (a modified Iowa Gambling Task, emotional go/no‐go) and five cool EF tasks, two switching tasks (visuospatial rule‐finding, geometric trails) and three working memory tasks (digit recall, selection and figure drawing). We performed confirmatory factor analysis testing whether a three‐factor, two‐factor hot‐cool, two‐factor working memory and inhibition/switching, or one‐factor EF model fitted the data better. The three‐factor (switching, inhibition and working memory) model had the best local and global fit (χ2 (11) 24.21, p = 0.012; RMSEA 0.036; CFI 0.920; CD 0.617). We demonstrated the feasibility of OCS‐EF administration by trained laypeople, the tripartite structure of EF amongst adolescent females and the factorial validity of OCS‐EF in this population and context. OCS‐EF tablet‐based cognitive assessment tool can be administered by trained laypeople and is a valid tool for assessing cognition at scale amongst adolescents in rural South Africa and similar environments.
Therapeutic dendritic cell cancer vaccines in hematologic malignancies
Authors: Bindal Poorva , Rosenblatt Jacalyn , Avigan David
Published: May 2021

Tumor cells present antigen in the context of negative costimulation and immunosuppressive factors, resulting in the inhibition of T cell activation and immune tolerance. Dendritic cells (DCs) are a complex network of antigen presenting cells that play a critical role in maintaining the equilibrium between immune activation directed against pathogens and tolerance necessary to prevent damage mediated by autoreactive T cell clones. DCs uniquely induce primary immune responses through the constitutive and enhanced expression of positive costimulatory molecules and inflammatory cytokines necessary for T cell activation. In this context, the design of a cancer vaccine is based on the effective presentation tumor associated antigens to evoke an antigen specific activated T cell response, and importantly, immune memory. As such, DCs have played a major role in the development of cancer vaccine therapy as critical mediators of antigen presentation reversing a major component of tumor mediated immune suppression. DC based vaccines have involved the loading of individual tumor associated antigens or the use of whole tumor cells and have demonstrated potent induction of tumor specific immunity. The correlation of immune response with clinical outcome and integration of DC vaccines with other immune based therapy is currently being explored.
Sparking collaboration and instilling core competencies through training a statewide workforce in Infant Mental Health: Report from the field
Authors: Dealy Jennifer , Robinson JoAnn , Eaves Tanika , Maderia Heidi
Published: May 2021

Fostering collaboration and instilling core competencies across the diverse Infant Mental Health systems and understanding their training needs are crucial endeavors to support the delivery of evidence‐based care and treatment continuity for infants and their families. This paper details the Connecticut Association for Infant Mental Health's use of a comprehensive infant mental health training series as a vehicle to achieve these aims. The training series, and the steps taken to execute and evaluate it are described to provide a framework for future collaborative training initiatives. Evaluation efforts were designed to address knowledge sought and gained and included pre and posttraining tests, participant reports of their training goals and needs, and interviews with trainers regarding the series’ strengths and limitations. Findings suggest significant improvements in participants’ knowledge of training content across trainings. Participants indicated a desire for trainings on working with the whole family and their plan to integrate skills from the training into their work. Recommendations from trainers and evaluators are provided to spark future trainings and collaborative efforts.
Novel composite scaffolds based on alginate and Mg‐doped calcium phosphate fillers: Enhanced hydroxyapatite formation under biomimetic conditions
Authors: Stojkovska Jasmina , Zvicer Jovana , Andrejevic Milica , Janackovic Djordje , Obradovic Bojana , Veljovic Djordje N.
Published: May 2021

In the present study, we synthesized hydroxyapatite (HAP) powders followed by the production of alginate based macroporous scaffolds with the aim to imitate the natural bone structure. HAP powders were synthesized by using a hydrothermal method, and after calcination, dominant phases in the powders, undoped and doped with Mg2+ were HAP and β‐tricalcium phosphate, respectively. Upon mixing with Na‐alginate, followed by gelation and freeze‐dying, highly macroporous composite scaffolds were obtained with open and connected pores and uniformly dispersed mineral phase as determined by scanning electron microscopy. Mechanical properties of the scaffolds were influenced by the composition of calcium phosphate fillers being improved as Ca2+ concentration increased while Mg2+ concentration decreased. HAP formation within all scaffolds was investigated in simulated body fluid (SBF) during 28 days under static conditions while the best candidate (Mg substituted HAP filler, precursor solution with [Ca + Mg]/P molar ratio of 1.52) was investigated under more physiological conditions in a biomimetic perfusion bioreactor. The continuous SBF flow (superficial velocity of 400 μm/s) induced the formation of abundant HAP crystals throughout the scaffolds leading to improved mechanical properties to some extent as compared to the initial scaffolds. These findings indicated potentials of novel biomimetic scaffolds for use in bone tissue engineering.
AnARHGAP25variant links aberrantRac1function to early‐onset skeletal fragility
Authors: Mäkitie Riikka E. , Henning Petra , Jiu Yaming , Kämpe Anders , Kogan Konstantin , Costantini Alice , Välimäki Ville‐Valtteri , Medina‐Gomez Carolina , Pekkinen Minna , Salusky Isidro B. , Schalin‐Jäntti Camilla , Haanpää Maria K. , Rivadeneira Fernando , Bassett John H. Duncan , Williams Graham R. , Lerner Ulf H. , Pereira Renata C. , Lappalainen Pekka , Mäkitie Outi
Published: May 2021

Ras homologous guanosine triphosphatases (RhoGTPases) control several cellular functions, including cytoskeletal actin remodeling and cell migration. Their activities are downregulated by GTPase‐activating proteins (GAPs). Although RhoGTPases are implicated in bone remodeling and osteoclast and osteoblast function, their significance in human bone health and disease remains elusive. Here, we report defective RhoGTPase regulation as a cause of severe, early‐onset, autosomal‐dominant skeletal fragility in a three‐generation Finnish family. Affected individuals (n = 13) presented with multiple low‐energy peripheral and vertebral fractures despite normal bone mineral density (BMD). Bone histomorphometry suggested reduced bone volume, low surface area covered by osteoblasts and osteoclasts, and low bone turnover. Exome sequencing identified a novel heterozygous missense variant c.652G>A (p.G218R) inARHGAP25, encoding a GAP for Rho‐family GTPase Rac1. Variants in theARHGAP255′ untranslated region (UTR) also associated with BMD and fracture risk in the general population, across multiple genomewide association study (GWAS) meta‐analyses (lead variant rs10048745).ARHGAP25messenger RNA (mRNA) was expressed in macrophage colony‐stimulating factor (M‐CSF)–stimulated human monocytes and mouse osteoblasts, indicating a possible role for ARHGAP25 in osteoclast and osteoblast differentiation and activity. Studies on subject‐derived osteoclasts from peripheral blood mononuclear cells did not reveal robust defects in mature osteoclast formation or resorptive activity. However, analysis of osteosarcoma cells overexpressing the ARHGAP25 G218R‐mutant, combined with structural modeling, confirmed that the mutant protein had decreased GAP‐activity against Rac1, resulting in elevated Rac1 activity, increased cell spreading, and membrane ruffling. Our findings indicate that mutated ARHGAP25 causes aberrant Rac1 function and consequently abnormal bone metabolism, highlighting the importance of RhoGAP signaling in bone metabolism in familial forms of skeletal fragility and in the general population, and expanding our understanding of the molecular pathways underlying skeletal fragility. © 2021 The Authors.JBMR Pluspublished by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Modification of COL1A1 in Autologous Adipose Tissue-Derived Progenitor Cells Rescues the Bone Phenotype in a Mouse Model of Osteogenesis Imperfecta
Authors: Liu Yi , Wang Zihan , Ju Mingyan , Zhao Yuxia , Jing Yaqing , Li Jiaci , Shao Chenyi , Fu Ting , Lv Zhe , Li Guang
Published: May 2021

Osteogenesis imperfecta (OI) is a congenital genetic disorder mainly manifested as bone fragility and recurrent fracture. Mutation of COL1A1/COL1A2 genes encoding the type I collagen are most responsible for the clinical patients. Allogenic mesenchymal stem cells (MSCs) provide the potential to treat OI through differentiation into osteoblasts. Autologous defective MSCs have not been utilized in OI treatment mainly because of their impaired osteogenesis, but the latent mechanism has not been well understood. Here, the relative signaling abnormality of adipose-derived mesenchymal stem cells (ADSCs) isolated from OI type I mice (Col1a1+/−365 mice) was explored. Autologous ADSCs transfected by retrovirus carrying human COL1A1 gene was first utilized in OI therapy. The results showed that decreased activity of Yes-associated protein (YAP) due to hyperactive upstream Hippo kinases greatly contributed to the weakened bone-forming capacity of defective ADSCs. Recovered collagen synthesis of autologous ADSCs by COL1A1 gene modification normalized Hippo/YAP signaling and effectively rescued YAP-mediated osteogenesis. And the COL1A1 gene engineered autologous ADSCs efficaciously improved the microstructure, enhanced the mechanical properties and promoted bone formation of Col1a1+/−365 mice after femoral bone marrow cavity delivery and might serve as an alternative source of stem cells in OI treatment. © 2021 American Society for Bone and Mineral Research (ASBMR).
Expression profiles of circular RNAs in colon biopsies from Crohn's disease patients by microarray analysis
Authors: Hu Yu‐an , Zhu Yan , Liu Guorui , Yao Xinyue , Yan Xiaoling , Yang Yang , Wang Weiping , Zou Xiaoping , Li Xiaojun
Published: May 2021

Background

Circular RNAs (circRNAs) are involved in various diseases and serve as biomarkers. The present study aimed to investigate unique expression profiles of circRNAs in colon tissues of Crohn's disease (CD) and search novel biomarkers for the diagnosis.

Methods

Differentially expressed (DE) circRNAs in biopsies from four CD patients, four ulcerative colitis (UC) patients, and four healthy controls (HC) were screened by microarray. Hsa_circ_0062142 and hsa_circ_0001666 were verified in another expanded validation cohort. Bioinformatics analysis was applied to predict the function of two DE circRNAs. Receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic value of CD.

Results

The top 10 upregulated circRNAs in CD compared with HC were hsa_circ_0000691, hsa_circ_0001666, hsa_circ_0004183, hsa_circ_0009024, hsa_circ RNA_405324, hsa_circ_0002003, hsa_circ_0085323, hsa_circ_0040994, hsa_circ_0062142, and hsa_circ_0048148; the top 10 downregulated circRNAs were hsa_circ_0049356, hsa_circ RNA_405443, hsa_circ RNA_403556, hsa_circ_0092328, hsa_circ_0003979, hsa_circ_0074491, hsa_circ_0023461, hsa_circ RNA_406237, hsa_circ_0034044, and hsa_circ RNA_400564 (fold change in descending order). The expression levels of hsa_circ_0001666 and hsa_circ_0062142 in CD were significantly higher than those in UC and HC (p < 0.01). ROC curves suggested the favorable diagnostic value of hsa_circ_0062142 and hsa_circ_0001666 (AUC = 0.803 and 0.858, respectively, p < 0.01). In silico analysis indicated that these circRNAs may be involved in the progress of CD.

Conclusion

Hsa_circ_0062142 and hsa_circ_0001666 may play critical roles in the pathogenesis and serve as potential biomarkers of CD.
The role and significance of angiotensin‐converting enzyme 2 peptides in the treatment of coronavirus disease 2019
Authors: Liu Yang , He Huanzhong , Huang Huilian
Published: May 2021

Since the end of 2019, coronavirus disease 2019 (COVID‐19) caused by the novel coronavirus (2019‐nCoV) posed a serious threat to human health and life. Therefore, the discovery of drugs that can effectively prevent and treat COVID‐19 is urgently warranted. In this article, the role and significance of angiotensin‐converting enzyme 2 in drug development and the treatment of COVID‐19 are discussed. It was found that the binding of ACE2 to SARS‐CoV‐2‐RBD involved two core regions (31st and 353rd lysine) and 20 amino acids of the ACE2 protein. The mutation of these amino acids could lead to a great change of the binding ability of ACE2 and SARS‐CoV‐2‐RBD. This information was important for us to find more efficient ACE2 peptides to block the 2019‐nCoV infection. So during this study, we summarized the role of ACE2 in the regulation of 2019‐nCoV infection and stress, and hypothesized that the development and optimization of ACE2 peptide can effectively block 2019‐nCoV infection and reliably treat the COVID‐19.
A culture of care: How Lotus House Women's Shelter heals program participants through genuineness, space, high expectations, dignity, individualized attention, and community
Authors: Eaton Asia A. , Stephens Dionne P. , Ruvalcaba Yanet , Banks Jasmine ,   Sundari Foundation Inc.
Published: May 2021

The present study was designed to examine perceptions of Lotus House Women's Shelter from the perspective of former program participants, for the purpose of informing shelter programming and policies. Our qualitative research followed a community‐based participatory research framework. Fifty diverse women graduates of Lotus House Women's Shelter participated in eight focus groups to discuss their experiences with Lotus House and other shelters. Findings from this study highlight the elements that create a “culture of care” within an organization. Participants described Lotus House shelter culture as genuine, defined by dignity and respect, having high expectations for guest independence and accountability, giving space to rest and recuperate, recognizing and accommodating individual needs and experiences, and fostering a sense of community. Creating an organizational “culture of care” is an avenue by which any shelter or related organization can enhance the experience of program participants.
The new periodontal disease classification: Level of agreement on diagnoses and treatment planning at various dental education levels
Authors: Abou‐Arraj Ramzi V. , Kaur Maninder , Alkhoury Shadi , Swain Thomas A. , Geurs Nicolaas C. , Souccar Nada M.
Published: May 2021

Purpose/objectives

Using the periodontal diseases classification published in 2018, this study evaluated the level of agreement among predoctoral and postgraduate students of different education levels and specialties in the diagnosis and treatment planning of periodontal conditions.

Methods

Second‐year (D2) and fourth‐year (D4) dental students, postgraduate orthodontic students (OS), and periodontology students (PS) were presented with an anonymous survey of 10 cases, each with five choices of diagnosis and seven therapeutic approaches. The cases included a patient summary, photographs, radiographs, periodontal charting, and ranged from health to periodontitis. Consensus diagnosis, used as a gold standard, was established between two experienced periodontists. Diagnosis and treatment choices for each case were compared across educational groups using Fisher's exact test. The level of agreement among educational groups was assessed using a multirater kappa coefficient.

Results

The survey was completed in 2020 with a 72.4% overall response rate (57‐D2, 45‐D4, 17‐OS, and 12‐PS). The overall level of agreement on diagnosis was fair (κ = 0.24, p <.0001) with PS showing the most agreement (κ = 0.55, p <.0001). There were tendencies to prioritize stage over grade and extent in assigning diagnoses and to overdiagnose disease severity and underdiagnose localized periodontitis. Nonsurgical periodontal therapies had the highest overall agreement (κ = 0.63 for scaling/root planing and κ = 0.44 for maintenance, p <.0001). Response distribution per case and per level of education indicated that PS more consistently agreed with the gold standard than any other group.

Conclusions

OS, D2, and D4 students demonstrated inferior agreement levels compared to PS, successfully recognized health from disease, suggested appropriate treatment plans, and tended to overdiagnose milder periodontal conditions.
Diagnostic challenge of chlamydial Fitz‐Hugh‐Curtis syndrome and cervicitis complicated by appendicitis: Case report
Authors: Ishimaru Naoto , Kanzawa Yohei , Nakajima Takahiro , Seto Hiroyuki , Ando Masayuki , Kinami Saori
Published: May 2021

Our patient had appendicitis complicated by Chlamydia trachomatis‐induced Fitz‐Hugh‐Curtis syndrome and cervicitis. Differential diagnosis was challenging. A 22‐year‐old Japanese woman was febrile and presented with vomiting and subsequent abdominal pain. She had unprotected sexual intercourse with multiple partners. She had high Alvarado score and lack of cervical motion pain, despite cervical inflammation. Noncontrast CT showed enlarged appendix. Laparoscopic appendectomy revealed acute suppurative appendicitis and perihepatic adhesion. Cervical PCR assay was positive for C. trachomatis. She remained febrile but defervesced after azithromycin therapy. Clinicians should confirm whether females with abdominal pain are sexually active in view of screening for C. trachomatis.
Real‐world data on treatment concepts in classical Hodgkin lymphoma in Sweden 2000–2014, focusing on patients aged >60 years
Authors: Wahlin Björn Engelbrekt , Övergaard Ninja , Peterson Stefan , Digkas Evangelos , Glimelius Ingrid , Lagerlöf Ingemar , Johansson Ann‐Sofie , Palma Marzia , Hansson Lotta , Linderoth Johan , Goldkuhl Christina , Molin Daniel
Published: May 2021

Treatment for patients > 60 years with classical Hodgkin lymphoma (cHL) is problematic; there is no gold standard, and outcome is poor. Using the Swedish Lymphoma Registry, we analysed all Swedish patients diagnosed with cHL between 2000 and 2014 (N = 2345; median age 42 years; 691 patients were >60 years). The median follow‐up time was 6.7 years. Treatment for elderly patients consisted mainly of ABVD or CHOP, and the younger patients were treated with ABVD or BEACOPP (with no survival difference). In multivariable analysis of patients > 60 years, ABVD correlated with better survival than CHOP (p = 0.027), and ABVD became more common over time among patients aged 61–70 years (p = 0.0206). Coinciding with the implementation of FDG‐PET/CT, the fraction of advanced‐stage disease increased in later calendar periods, also in the older patient group. Survival has improved in cHL patients > 60 years (p = 0.027), for whom ABVD seems superior to CHOP.
Socioeconomic cost of AML in Sweden—A population‐based study using multiple nation‐wide registers
Authors: Hernlund Emma , Redig Josefine , Paulsson Björn , Rangert Derolf Åsa , Höglund Martin , Vertuani Simona , Juliusson Gunnar
Published: May 2021

Acute myeloid leukemia (AML) is associated with a high economic and clinical burden. Recently novel therapies have been added to standard treatment regimens. Here, we evaluated the economic impact of AML up until the introduction of these novel therapies. Individual data on 2954 adult patients diagnosed from 2007 to 2015 from five Swedish national population‐based registers were used, enabling analyses from diagnosis to either death or 5‐year follow‐up for survival, inpatient and outpatient costs, costs of prescribed drugs, sick leave, and early retirement. Costs per patient were stratified by age group, treatment options, and FLT3‐ITD status. The expected 5‐year costs per patient differed substantially between age groups. Patients aged 18–59 years had an expected mean cost per patient of €170,748, while age groups 60–69 years, 70–79 years, and >80 years incurred an expected mean cost of €92,252, €48,344, and €24,118, respectively, over 5 years. Patients <60 years undergoing stem cell transplantation had the highest costs (€228,525 over 5 years). About 60% of costs for these patients were from hospitalizations and 20% from sick leave and early retirement; cost per day was highest from the first admission to complete remission. This study provides a baseline for socioeconomic evaluations of novel therapies in AML in Sweden.
Synthesis and antitumor activity of novel pyridino[2,3‐d]pyrimidine urea derivatives
Authors: Chen Dongmei , Chen Yumei , Yang Di , Zheng Zhaopeng , Zhou Zhixu
Published: May 2021

A series of novel N‐(3‐((6‐bromopyrido[2,3‐d]pyrimidin‐4‐yl)oxy)phenyl)pyrrolidine‐1‐carboxamide and 1‐(3‐((6‐bromopyrido[2,3‐d]pyrimidin‐4‐yl)oxy)phenyl)‐3‐propylurea derivatives were synthesized. Their antitumor activities against human breast carcinoma cells (MCF‐7) and human colon cancer cells (HCT‐116) in vitro were evaluated, using sorafenib as a positive control drug. Anticancer bioassays indicated that several compounds exhibited appreciable anticancer activity against MCF‐7 and HCT‐116 cells. Particularly, compounds 9g and 8b demonstrated the most significant inhibitory effect against HCT‐116 and MCF‐7 cells, with inhibition ratios of 25.56% and 26.46%, respectively. Additionally, the synthesized pyridine[2,3‐d]pyrimidine derivatives containing a urea group moieties exhibited antitumor activities against MCF‐7 and HCT‐116 cells in vitro.
A cluster‐randomized controlled trial of a combination HIV risk reduction and microfinance intervention for female sex workers who use drugs in Kazakhstan
Authors: El‐Bassel Nabila , McCrimmon Tara , Mergenova Gaukhar , Chang Mingway , Terlikbayeva Assel , Primbetova Sholpan , Kuskulov Azamat , Baiserkin Bauyrzhan , Denebayeva Alfiya , Kurmetova Kulpan , Witte Susan S.
Published: May 2021

Introduction

Female sex workers (FSW) who use drugs are a key population at risk of HIV in Kazakhstan, and face multiple structural barriers to HIV prevention. More research is needed on the role of structural interventions such as microfinance (MF) in reducing HIV risk. This paper describes the results of a cluster‐randomized controlled trial to test the efficacy of a combination HIVRR + MF intervention in reducing biologically confirmed STIs and HIV risk behaviours.

Methods

This study took place from May 2015 to October 2018 in two cities in Kazakhstan. We screened 763 participants for eligibility and enrolled 354 FSW who use drugs. Participants were randomized in cohorts to receive either a four‐session HIVRR intervention, or that same intervention plus 30 additional sessions of financial literacy training, vocational training and asset‐building through a matched‐savings programme. Repeated behavioural and biological assessments were conducted at baseline, 3‐, 6‐ and 12‐months post‐intervention. Biological and behavioural primary outcomes included HIV/STI incidence, sexual risk behaviours and drug use risk behaviours, evaluated over the 12‐month period.

Results

Over the 12‐month follow‐up period, few differences in study outcomes were noted between arms. There was only one newly‐detected HIV case, and study arms did not significantly differ on any STI incidence. At post‐intervention assessments compared to baseline, both HIVRR and HIVRR + MF participants significantly reduced sexual and drug use risk behaviours, and showed improvements in financial outcomes, condom use attitudes and self‐efficacy, social support, and access to medical care. In addition, HIVRR + MF participants showed a 72% greater reduction in the number of unprotected sex acts with paying partners at the six‐month assessment (IRR = IRR = 0.28, 95% CI = 0.08, 0.92), and a 10% greater reduction in the proportion of income from sex work at the three‐month assessment (b = −0.10, 95% CI = −0.17, −0.02) than HIVRR participants did. HIVRR + MF participants also showed significantly improved performance on financial self‐efficacy compared to HIVRR over the 12‐month follow‐up period.

Conclusions

Compared to a combination HIVRR + MF intervention, a robust HIVRR intervention alone may be sufficient to reduce sexual and drug risk behaviours among FSW who use drugs. There may be structural limitations to the promise of microfinance for HIV risk reduction among this population.
Cerebrospinal fluid and serum interleukins 6 and 8 during the acute and recovery phase in COVID‐19 neuropathy patients
Authors: Manganotti Paolo , Bellavita Giulia , Tommasini Valentina , D′Acunto Laura , Fabris Martina , Cecotti Laura , Furlanis Giovanni , Sartori Arianna , Bonzi Lucia , Buoite Stella Alex , Pesavento Valentina
Published: May 2021

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID‐19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin‐6 (IL‐6) and IL−8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL‐6 and IL‐8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL‐8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL‐6 and IL‐8 as prognostic biomarkers in COVID‐19.
Design and performance of a dark‐field probe with confocal Raman spectroscopy for ophthalmic applications
Authors: Zhang Shuo , Erckens Roel J. , Jongsma Franciscus H.M. , Webers Carroll A.B. , Berendschot Tos T.J.M.
Published: May 2021

A dark‐field ophthalmic contact probe for analysis of aqueous humor (AH) was designed by ray tracing and constructed in quartz glass for experimental use as a prototype probe in a confocal Raman spectroscopic setup. The misalignment tolerance of this probe was theoretically evaluated, whereas the optical performance was experimentally evaluated by a concentration curve of the ocular drug phenylephrine HCl in an artificial eye model. The results indicated a ninefold improvement in misalignment tolerance and a 36‐fold improvement in the signal‐to‐noise ratio at the phenylephrine HCl 1002 cm−1 peak compared with a previous design. The prototype showed a good linear fit with the phenylephrine HCl concentration, with an R2 of 0.996. Phenylephrine HCl concentration down to 0.1% is detectable.
Sonographic Measurement of Dynamic Horizontal Instability in Acromioclavicular Joint Instability
Authors: Bockmann Benjamin , Venjakob Arne Johannes , Thrasyvoulidis Giorgos , Holschen Malte , Schulte Tobias Ludger , Nebelung Wolfgang
Published: May 2021

Objective

Dynamic horizontal instability is considered to be the main reason for poor outcome after treatment for acromioclavicular (AC) joint instability. In this study, we describe a simple technique to quantify this pathology via sonography.

Methods

Thirty‐six shoulders from 18 patients with ac joint instabilities were examined using modified Alexander views and a standardized sonographic examination. On the Alexander views, overlap of acromion and clavicle (OLAC), glenoid center to posterior clavicle distance (GCPC), and lateral extension (LE) were measured. Afterwards, the results were analyzed and compared with sonography. Posterior translation of the clavicle and the difference of translation between healthy and injured shoulder were evaluated.

Results

The mean age of the patients was 39 ± 14 years (range 19–61 years). We included 4 (22%) Rockwood type 3, 1 (6%) Rockwood type 4, and 13 (72%) Rockwood type 5 lesions. Four (22%) patients were female and 14 (78%) male patients. Posterior clavicle translation of the injured shoulder correlated strongly between OLAC and sonography (r = −0.514, P = .029), and the difference of translation between healthy and injured shoulder correlated very strongly between LE and sonography (r = 0.737, P < .001).

Conclusion

The sonographic measurement technique for horizontal instability presented in this work could help detect horizontal instabilities. While the observation of dynamic horizontal displacement is a strength of this technique, measurements are hindered in cases of high coracoclavicular distances.

Level of Evidence

Level III—retrospective cohort study.
LncRNA CCAT1 downregulation increases the radiosensitivity of non‐small cell lung cancer cells
Authors: Wang Zhao
Published: May 2021

This study aims to investigate if the radiosensitivity of non‐small cell lung cancer (NSCLC) cells can be regulated by long noncoding RNA (lncRNA) colon cancer associated transcript1 (CCAT1). CCAT1 was detected by quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) in NSCLC cells (A549, H1299, SK‐MES1, H460, and H647) and human bronchial epithelial cells (16HBE). H460 and A549 cells were then selected for the determination of CCAT1 expression after exposure to radiation (0, 2, 4, 6 Gy) at different time points (0, 6, 12, 24 h). Colony forming assay was performed to evaluate the effects of CCAT1 siRNA or pcDNA3.1‐CCAT1 vector on the radiosensitivity of H460 and A549 cells. Then, flow cytometry, western blotting and qRT‐PCR were also conducted. CCAT1 was increased in NSCLC cells when compared with 16HBE cells, which was declined in a time‐ and dosage‐dependent manner after exposure to radiation. The H460 and A549 cell colonies were decreased and the γ‐H2AX expression was elevated with the increase of radiation dosage, which was more obvious in those transfected with CCAT1 siRNA. CCAT1 downregulation arrested NSCLC cells at G2/M phase. Moreover, the enhanced apoptosis of radiotherapy‐treated NSCLC cells with reductions of p‐p38/p38, p‐ERK/ERK, and p‐JNK/JNK was promoted by siCCAT1, but it was reversed by pcDNA3.1‐CCAT1 vector. Inhibiting CCAT1 regulated cell cycle, DNA damage and apoptosis of NSCLC cells, and affected MAPK pathway, eventually improving the radiosensitivity of NSCLC.
Benign paroxysmal positional vertigo and vestibular impairment among older adults with dizziness
Authors: Lindell Ellen , Karlsson Therese , Kollén Lena , Johansson Mia , Finizia Caterina
Published: May 2021

Objective

This article aimed to investigate older adults visiting a geriatric institution for a bone density measurement who reported dizziness on a daily or weekly basis (but who are not seeking care for dizziness), according to BPPV, vestibular function, walking abilities, and frequency of falls.

Methods

Patients coming for a bone density measurement answered questions regarding occurrence of dizziness. Patients having dizziness on a daily or weekly basis were considered eligible for the study and invited for investigation at the Ear, Nose, and Throat clinic at Södra Älvsborg Hospital, Sweden. The patients answered questions about history of dizziness, medications, and comorbidities. They were also investigated for BPPV, vestibular deficits using the video head impulse test (vHIT), walking speed, Timed Up and Go test (TUG), and for perception of verticality and horizontality and Romberg test.

Results

A total of 55 patients with dizziness were included. Fifteen (27%) were diagnosed with BPPV. Forty (73%) patients reported falling during the previous year, including 11 with BPPV. Dizziness when turning in bed was more common among patients with BPPV and increased the risk of BPPV 8‐fold.

Conclusion

BPPV is common among older adults with dizziness, including among those not seeking medical care. It is important to identify older adults with BPPV and treat the condition since BPPV may contribute to falls. Asking about dizziness when turning in bed can help to distinguish patients with increased risk for BPPV and older adults with dizziness should be investigated for BPPV even when typical history is lacking.

Level of evidence: 4
Design of Suspended Melt Electrowritten Fiber Arrays for Schwann Cell Migration and Neurite Outgrowth
Authors: Hrynevich Andrei , Achenbach Pascal , Jungst Tomasz , Brook Gary A. , Dalton Paul D.
Published: May 2021

In this study, well‐defined, 3D arrays of air‐suspended melt electrowritten fibers are made from medical grade poly(ɛ‐caprolactone) (PCL). Low processing temperatures, lower voltages, lower ambient temperature, increased collector distance, and high collector speeds all aid to direct‐write suspended fibers that can span gaps of several millimeters between support structures. Such processing parameters are quantitatively determined using a “wedge‐design” melt electrowritten test frame to identify the conditions that increase the suspension probability of long‐distance fibers. All the measured parameters impact the probability that a fiber is suspended over multimillimeter distances. The height of the suspended fibers can be controlled by a concurrently fabricated fiber wall and the 3D suspended PCL fiber arrays investigated with early post‐natal mouse dorsal root ganglion explants. The resulting Schwann cell and neurite outgrowth extends substantial distances by 21 d, following the orientation of the suspended fibers and the supporting walls, often generating circular whorls of high density Schwann cells between the suspended fibers. This research provides a design perspective and the fundamental parametric basis for suspending individual melt electrowritten fibers into a form that facilitates cell culture.
Robust Electrospun Nanofibers from Chemosynthetic Poly(4‐hydroxybutyrate) as Artificial Dural Substitute
Authors: Ma Huihui , Sun Yilin , Tang Ying , Shen Yong , Kan Ze , Li Qing , Fang Sha , Lu Yingxi , Zhou Xianfeng , Li Zhibo
Published: May 2021

Bioresorbable poly(4‐hydroxybutyrate) (P4HB) may fulfill the specific requirements that are necessary for a dural substitute, including its high elasticity, long‐term strength retention properties, and the biocompatibility without significant accumulation of acidic degradation products. However, commercial P4HB can only be produced by the bacterial fermentation, which limits its applications in the cerebrospinal system due to higher endotoxin restriction. Meanwhile, P4HB can be prepared via the ring‐opening polymerization of γ‐butyrolactone. In this contribution, high molecular weight P4HB from chemosynthesis is electrospun into fibrous membrane, showing good mechanical properties that match the natural dura mater. Such P4HB membrane induces fast cellular migration, adhesion, and proliferation of fibroblasts in vitro. Subcutaneous implantation in rats demonstrates excellent biocompatibility of the P4HB membrane with proper biodegradation behaviors. After implantation in the rabbit dural defect model as an onlay graft, the P4HB membranes prevent cerebrospinal fluid leakage and regenerate dura tissue without detecting any local or systematic infections or foreign body responses. Thus, the electrospun P4HB membranes may be particularly useful as artificial dural substitutes to induce wound closure and tissue regeneration, which will be of great benefit to neurosurgery in the future.
Molecular‐Level Interactions of Nanodisc‐Forming Copolymers Dissected by EPR Spectroscopy
Authors: Eisermann Jana , Hoffmann Matthias , Schöffmann Florian A. , Das Manabendra , Vargas Carolyn , Keller Sandro , Hinderberger Dariush
Published: May 2021

This study focuses on analyzing the noncovalent interaction patterns between three lipid‐nanodisc‐forming polymers and nitroxide radicals which are used as small organic tracer molecules. Besides the negatively charged polymers diisobutylene/maleic acid (DIBMA) and styrene/maleic acid (SMA) (2:1), the solvation behavior of a newly synthesized zwitterionic styrene/maleic amide sulfobetaine copolymer named SMA‐sulfobetaine (SB) is characterized. The applied spin probes vary in their respective chemical structure, allowing the report of different local micropolarities and nanoscopic regions by recording temperature‐dependent continuous‐wave electron paramagnetic resonance (CW EPR) spectra. In combination with light scattering experiments, a nanoscopic interpretation of the dominant polymer/guest molecule interaction patterns is provided. The results indicate that in SMA and DIBMA, ionic interactions dominate the interaction patterns with other molecules. In SMA‐SB, the zwitterionic side chains mainly induce a dynamic assembly with guest molecules due to weaker noncovalent interactions. Depending on the applied spin probe, temperature‐dependent CW EPR measurements reveal nanoscopic cloud points depending on the interaction patterns with SMA‐SB which can occur more than 20 °C below its macroscopically observed upper critical solution temperature. Finally, the detailed dissection of interaction patterns may provide a better understanding that may even allow tuning the polymers’ properties for use in lipid nanodisc formation.
Directed Assembly of Cellulose Nanocrystals in Their Native Solid‐State Template of a Processed Fiber Cell Wall
Authors: Solala Iina , Driemeier Carlos , Mautner Andreas , Penttilä Paavo A. , Seitsonen Jani , Leppänen Miika , Mihhels Karl , Kontturi Eero
Published: May 2021

Nanoparticle assembly is intensely surveyed because of the numerous applications within fields such as catalysis, batteries, and biomedicine. Here, directed assembly of rod‐like, biologically derived cellulose nanocrystals (CNCs) within the template of a processed cotton fiber cell wall, that is, the native origin of CNCs, is reported. It is a system where the assembly takes place in solid state simultaneously with the top‐down formation of the CNCs via hydrolysis with HCl vapor. Upon hydrolysis, cellulose microfibrils in the fiber break down to CNCs that then pack together, resulting in reduced pore size distribution of the original fiber. The denser packing is demonstrated by N2 adsorption, water uptake, thermoporometry, and small‐angle X‐ray scattering, and hypothetically assigned to attractive van der Waals interactions between the CNCs.
Clinical value for the detection of fetal chromosomal deletions/duplications by noninvasive prenatal testing in clinical practice
Authors: Gou Lingshan , Suo Feng , Wang Yi , Wang Na , Wu Qin , Hu Shunan , Wang Peng , Gu Lize , Zhang Man , Wang Chuanxia , Zhang Yan , Yin Xin , Zhang Peng , Xu Jian , Wang Xingqi , Gu Maosheng
Published: May 2021

Objective

This study was to report the experiences on the clinical value of noninvasive prenatal testing (NIPT) for the screening of fetal chromosomal deletions/duplications.

Methods

We performed a retrospective analysis of a cohort of 20,439 pregnancies undergoing NIPT from March 2017 to September 2020 at a single center. Patients with positive NIPT results for fetal chromosomal deletions or duplications had options of invasive diagnostic testing or no further testing. The data were complied from all cases with positive NIPT results for chromosomal deletions/duplications. The positive predictive value (PPV) was calculated from tabulated data.

Results

In this cohort, positive NIPT results for fetal chromosomal deletions/duplications were found in 60 pregnant women. Of the positive samples, further invasive testing was performed in 39 cases, in which 9 cases were found to be true positive. The overall PPV for chromosomal deletions/duplications was 23.1%. In addition, fetal structural anomaly was found by ultrasound examination in three cases, in which the chromosomal deletions/duplications of three cases were not verified. Moreover, an unexpected pathogenic 8p23.3 deletion was identified by invasive testing in 1 fetus with a false positive NIPT screen for 3q27.3q29 duplication.

Conclusions

In summary, positive NIPT results of chromosomal deletions/duplications were not uncommon in clinical practice, whereas the PPV for the testing was low. Hence, potential risks and high percentage of false positives for these abnormal NIPT results might be informed to pregnant women before the choice made of invasive testing.