bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV prevalence, testing and treatment among men who have sex with men through engagement in virtual sexual networks in Kenya: a cross‐sectional bio‐behavioural study
Authors: Bhattacharjee Parinita , Isac Shajy , Musyoki Helgar , Emmanuel Faran , Olango Kennedy , Kuria Samuel , Ongaro Martin K , Walimbwa Jeffrey , Musimbi Janet , Mugambi Mary , Kaosa Shem , Kioko Japheth , Njraini Margret , Melon Memory , Onyoni Juddie , Bartilol Kigen , Becker Marissa , Lorway Robert , Pickles Michael , Moses Stephen , Blanchard James , Mishra Sharmistha
Published: June 2020

Introduction

In Kenya, men who have sex with men (MSM) are increasingly using virtual sites, including web‐based apps, to meet sex partners. We examined HIV testing, HIV prevalence, awareness of HIV‐positive status and linkage to antiretroviral therapy (ART), for HIV‐positive MSM who solely met partners via physical sites (PMSM), compared with those who did so in virtual sites (either solely via virtual sites (VMSM), or via both virtual and physical sites (DMSM)).

Methods

We conducted a cross‐sectional bio‐behavioural survey of 1200 MSM, 15 years and above, in three counties in Kenya between May and July 2019, using random sampling of physical and virtual sites. We classified participants as PMSM, DMSM and VMSM, based on where they met sex partners, and compared the following between groups using chi‐square tests: (i) proportion tested; (ii) HIV prevalence and (iii) HIV care continuum among MSM living with HIV. We then performed multivariable logistic regression to measure independent associations between network engagement and HIV status.

Results

177 (14.7%), 768 (64.0%) and 255 (21.2%), of participants were classified as PMSM, DMSM and VMSM respectively. 68.4%, 70.4% and 78.5% of PMSM, DMSM and VMSM, respectively, reported an HIV test in the previous six months. HIV prevalence was 8.5% (PMSM), 15.4% (DMSM) and 26.7% (VMSM), p < 0.001. Among those living with HIV, 46.7% (PMSM), 41.5% (DMSM) and 29.4% (VMSM) were diagnosed and aware of their status; and 40.0%, 35.6% and 26.5% were on antiretroviral treatment. After adjustment for other predictors, MSM engaged in virtual networks remained at a two to threefold higher risk of prevalent HIV: VMSM versus PMSM (adjusted odds ratio 3.88 (95% confidence interval (CI) 1.84 to 8.17) p < 0.001); DMSM versus PMSM (2.00 (95% CI 1.03 to 3.87), p = 0.040).

Conclusions

Engagement in virtual networks is associated with elevated HIV risk, irrespective of individual‐level risk factors. Understanding the difference in characteristics among MSM‐seeking partners in different sites will help HIV programmes to develop subpopulation‐specific interventions.
Index and targeted community‐based testing to optimize HIV case finding and ART linkage among men in Zambia
Authors: Mwango Linah K , Stafford Kristen A , Blanco Natalia C , Lavoie Marie‐Claude , Mujansi Morley , Nyirongo Nasho , Tembo Kalima , Sakala Henry , Chipukuma Julian , Phiri Beauty , Nzangwa Carol , Mwandila Susan , Nkwemu Kennedy C , Saadani Ahmed , Mwila Annie , Herce Michael E , Claassen Cassidy W
Published: June 2020

Introduction

Current healthcare systems fail to provide adequate HIV services to men. In Zambia, 25% of adult men living with HIV were unaware of their HIV status in 2018, and 12% of those who were unaware of their HIV statu were not receiving antiretroviral therapy (ART) due to pervasive barriers to HIV testing services (HTS) and linkage to ART. To identify men and key and priority populations living with HIV in Zambia, and link them to care and treatment, we implemented the Community Impact to Reach Key and Underserved Individuals for Treatment and Support (CIRKUITS) project. We present HTS and ART linkage results from the first year of CIRKUITS.

Methods

CIRKUITS aimed to reach beneficiaries by training, mentoring, and deploying community health workers to provide index testing services and targeted community HTS. Community leaders and workplace supervisors were engaged to enable workplace HTS for men. To evaluate the effects of these interventions, we collected age‐ and sex‐disaggregated routinely collected programme data for the first 12 months of the project (October 2018 to September 2019) across 37 CIRKUITS‐supported facilities in three provinces. We performed descriptive statistics and estimated index cascades for indicators of interest, and used Chi square tests to compare indicators by age, sex, and district strata.

Results

Over 12 months, CIRKUITS tested 38,255 persons for HIV, identifying 10,974 (29%) new people living with HIV, of whom 10,239 (93%) were linked to ART. Among men, CIRKUITS tested 18,336 clients and identified 4458 (24%) as HIV positive, linked 4132 (93%) to ART. Men who tested HIV negative were referred to preventative services. Of the men found HIV positive, and 13.0% were aged 15 to 24 years, 60.3% were aged 25 to 39, 20.9% were aged 40 to 49 and 5.8% were ≥50 years old. Index testing services identified 2186 (49%) of HIV‐positive men, with a positivity yield of 40% and linkage of 88%. Targeted community testing modalities accounted for 2272 (51%) of HIV‐positive men identified, with positivity yield of 17% and linkage of 97%.

Conclusions

Index testing and targeted community‐based HTS are effective strategies to identify men living with HIV in Zambia. Index testing results in higher yield, but lower linkage and fewer absolute men identified compared to targeted community‐based HTS.
Identification of neuronal structures and pathways corresponding to clinical functioning in galactosemia
Authors: Ahtam Banu , Waisbren Susan E. , Anastasoaie Vera , Berry Gerard T. , Brown Matthew , Petrides Stephanie , Afacan Onur , Prabhu Sanjay P. , Schomer Donald , Grant P. Ellen , Greenstein Patricia E.
Published: June 2020

Classic galactosemia (OMIM# 230400) is an autosomal recessive disorder due to galactose‐1‐phosphate uridyltransferase deficiency. Newborn screening and prompt treatment with a galactose‐free diet prevent the severe consequences of galactosemia, but clinical outcomes remain suboptimal. Five men and five women with classic galactosemia (mean age = 27.2 ± 5.47 years) received comprehensive neurological and neuropsychological evaluations, electroencephalogram (EEG) and magnetic resonance imaging (MRI). MRI data from nine healthy controls (mean age = 30.22 ± 3.52 years) were used for comparison measures. Galactosemia subjects experienced impaired memory, language processing, visual‐motor skills, and increased anxiety. Neurological examinations revealed tremor and dysarthria in six subjects. In addition, there was ataxia in three subjects and six subjects had abnormal gait. Mean full scale IQ was 80.4 ± 17.3. EEG evaluations revealed right‐sided abnormalities in five subjects and bilateral abnormalities in one subject. Compared to age‐ and gender‐matched controls, subjects with galactosemia had reduced volume in left cerebellum white matter, bilateral putamen, and left superior temporal sulcus. Galactosemia patients also had lower fractional anisotropy and higher radial diffusivity values in the dorsal and ventral language networks compared to the controls. Furthermore, there were significant correlations between neuropsychological test results and the T1 volume and diffusivity scalars. Our findings help to identify anatomic correlates to motor control, learning and memory, and language in subjects with galactosemia. The results from this preliminary assessment may provide insights into the pathophysiology of this inborn error of metabolism.
Classic and new mediators for in vitro modelling of human macrophages
Authors: Luque-Martin Rosario , Mander Palwinder K , Leenen Pieter J M , Winther Menno P J
Published: June 2020

Macrophages are key immune cells in the activation and regulation of immune responses. These cells are present in all tissues under homeostatic conditions and in many disease settings. Macrophages can exhibit a wide range of phenotypes depending on local and systemic cues that drive the differentiation and activation process. Macrophage heterogeneity is also defined by their ontogeny. Tissue macrophages can either derive from circulating blood monocytes or are seeded as tissue-resident macrophages during embryonic development. In humans, the study of in vivo-generated macrophages is often difficult with laborious and cell-changing isolation procedures. Therefore, translatable, reproducible, and robust in vitro models for human macrophages in health and disease are necessary. Most of the methods for studying monocyte-derived macrophages are based on the use of limited factors to differentiate the monocytes into macrophages. Current knowledge shows that the in vivo situation is more complex, and a wide range of molecules in the tissue microenvironment promote and impact on monocyte to macrophage differentiation as well as activation. In this review, macrophage heterogeneity is discussed and the human in vitro models that can be applied for research, especially for monocyte-derived macrophages. We also focus on new molecules (IL-34, platelet factor 4, etc.) used to generate macrophages expressing different phenotypes.
Evaluation of human cartilage endplate composition using MRI: Spatial variation, association with adjacent disc degeneration, and in vivo repeatability
Authors: Wang Linshanshan , Han Misung , Wong Jason , Zheng Patricia , Lazar Ann A. , Krug Roland , Fields Aaron J.
Published: June 2020

Cartilage endplate (CEP) biochemical composition may influence disc degeneration and regeneration. However, evaluating CEP composition in patients remains a challenge. We used T2* mapping from ultrashort echo‐time (UTE) magnetic resonance imaging (MRI), which is sensitive to CEP hydration, to investigate spatial variations in CEP T2* values and to determine how CEP T2* values correlate with adjacent disc degeneration. Thirteen human cadavers (56.4 ± 12.7 years) and seven volunteers (36.9 ± 10.9 years) underwent 3T MRI, including UTE and T1ρ mapping sequences. Spatial mappings of T2* values in L4‐S1 CEPs were generated from UTE images and compared between subregions. In the abutting discs, mean T1ρ values in the nucleus pulposus were compared between CEPs with high vs low T2* values. To assess in vivo repeatability, precision errors in mean T2* values, and intraclass correlation coefficients (ICC) were measured from repeat scans. Results showed that CEP T2* values were highest centrally and lowest posteriorly. In the youngest individuals (<50 years), who had mild‐to‐moderately degenerated Pfirrmann grade II‐III discs, low CEP T2* values associated with severer disc degeneration: T1ρ values were 26.7% lower in subjects with low CEP T2* values (P = .025). In older individuals, CEP T2* values did not associate with disc degeneration (P = .39‐.62). Precision errors in T2* ranged from 1.7 to 2.6 ms, and reliability was good‐to‐excellent (ICC = 0.89‐0.94). These findings suggest that deficits in CEP composition, as indicated by low T2* values, associate with severer disc degeneration during the mild‐to‐moderate stages. Measuring CEP T2* values with UTE MRI may clarify the role of CEP composition in patients with mild‐to‐moderate disc degeneration.
Correlation of hip capsule morphology with patient symptoms from femoroacetabular impingement
Authors: Shaw Chace , Warwick Hunter , Nguyen Kevin H. , Link Thomas M. , Majumdar Sharmila , Souza Richard B. , Vail Thomas P. , Zhang Alan L.
Published: June 2020

The relationship between morphological characteristics of the hip capsule and patient symptoms in the setting of femoroacetabular impingement (FAI) is undefined. In this study, patients with symptomatic FAI prospectively underwent 3T magnetic resonance (MR) imaging of the affected hip and completed the hip disability and osteoarthritis outcome score (HOOS) to determine the correlation between hip capsule anatomy and patient symptoms. Anterior hip capsule volume, posterior capsule volume, anterior‐posterior capsule volume ratio, and proximal‐distal volume ratio in the anterior capsule were quantified and measured using axial‐oblique intermediate‐weighted 3D fast spin echo MR images. A total of 35 patients (35 hips) were included for analysis (mean age: 30.6 years; mean body mass index [BMI]: 24.9 kg/m2; 57% male). The mean alpha angle was 62.2° ± 4.7°, the mean anterior hip capsule volume was 1705.1 ± 450.3 mm3, the mean posterior hip capsule volume was 1284.8 ± 268.5 mm3, the mean anterior to posterior capsule volume ratio was 1.1 ± 0.39, and the mean proximal to distal volume ratio of the anterior capsule was 0.65 ± 0.28. There was no correlation between age, gender, or BMI, and any hip capsule characteristics. Worse scores on the HOOS pain scale were correlated with increased anterior to posterior volume ratio (r = −.38; 95% confidence interval: −0.06 to −0.63). In conclusion, hip capsule morphology correlates with patient symptoms in the setting of FAI as increased anterior capsular volume, relative to posterior capsular volume, is associated with greater patient pain.
Holocene coastal change at Luce Bay, South West Scotland
Authors: Smith David E. , Tipping Richard M. , Jordan Jason T. , Blackett Mathew
Published: June 2020

Coastal change during the Mid‐ to Late Holocene at Luce Bay, South West Scotland, is examined using morphological, stratigraphic and biostratigraphical techniques supported by radiocarbon dating. Deglaciation left extensive sediments, providing a source for depositional coastal landforms. Glacio‐isostatic uplift resulted in the registration of evidence for former relative sea levels (RSLs), which support the pattern of Holocene RSL change for the northern Irish Sea as determined by shoreline‐based Gaussian trend surface models. The rate of RSL rise was rapid from before ca. 8600 to ca. 7800 cal a
bp, but then slowed, changing by <3 m over the next 3000 years, a pattern reflected in the convergence of shorelines predicted in the models. By ca. 4400 cal a
bp RSL was falling towards present levels. As these changes were taking place, coastal barriers developed and dunes formed across them. In the West of the Bay, a lagoon forming to landward of the barriers and dunes acted as a sediment sink for dune sand. Changes in the coastal landscape influenced the occupation of the area by early human societies. This study illustrates the value of combining an understanding of process geomorphology, RSL and archaeology in studies of coastal change.
Correlation between the compensation time and the current deviation of organic LED pixel circuit
Authors: Lee Joon Ho , Kim Dae Hyun , Yang Joo Won , Moon Kook Chul , Lee Soo‐Yeon , Jeon Jae Hong , Kim Yong Sang , Park Kee Chan
Published: June 2020

A compensation circuit is necessary in each pixel of the organic light‐emitting diode (OLED) display to reduce the mura resulting from the nonuniform characteristics of the low‐temperature polycrystalline silicon thin‐film transistor (TFT). Recently, the mura becomes severe as the frame rate, display resolution, and the OLED efficacy improve. The low‐gray mura for the OLED current far below 1 nA is easily noticed, which is a critical issue of the high‐end mobile OLED display. We report the correlation between the deviation of OLED current due to the nonuniform TFT characteristics and the compensation time by in‐depth analysis employing the SPICE simulation of two well‐known pixel circuits. We have found that the compensation effect improves as the compensation time increases for low gray‐level current. On the contrary, the compensation effect deteriorates, and the deviation of OLED current intensifies for high gray‐level current as the compensation time increases too much. The quantitative analysis shows that the optimal compensation time depends on the targeted OLED current level and that the compensation effect is highest when the compensation time is such that the current of the driving TFT at the end of compensation period is several times smaller than the targeted OLED current during the light‐emitting period.
Oncologic safety of propeller flap and free flap in reconstruction after soft tissue sarcoma resection
Authors: Cha Han Gyu , Kang Min Kyu , Kim Wanlim , Lee Jong Seok , Hong Joon Pio , Suh Hyunsuk Peter
Published: June 2020

Background and Objectives

The propeller flap is a reliable option for reconstruction after soft tissue sarcoma resection. However, some parts of the resection margin may move away from its original position during flap rotation and thus can be excluded from the clinical target volume of adjuvant radiotherapy. This study aimed to evaluate local recurrence after soft tissue sarcoma resection with propeller flap or free flap reconstruction.

Methods

Patients who underwent resection of soft tissue sarcoma followed by a free flap or propeller flap reconstruction and adjuvant radiotherapy at a single institution were retrospectively reviewed.

Results

The 1‐ and 3‐year local control rates were 94.6% and 88.6% in the free flap group vs 90.6% and 87.5% in the propeller flap group, without statistical significance. There were no statistically significant differences in 5‐year local recurrence‐free survival (88.6% vs 87.5%) and disease‐free survival (82.5% vs 74.8%) between the groups.

Conclusions

Although there was no significant difference in local control and disease‐free survival rates between propeller flap and free flap reconstruction after soft tissue sarcoma resection, a multidisciplinary approach is needed to obtain surgical information for determining the accurate clinical target volume of adjuvant radiotherapy and the area for meticulous follow‐up postoperatively.
Endoscopic Findings in Male Prepubertal Choir Singers
Authors: Lee David R. , Weinrich Barbara , Zacharias Stephanie , LeBorgne Wendy , Beckmeyer Janet , Eanes Christopher , Tabangin Meredith E. , de Alarcon Alessandro
Published: June 2020

Objectives/Hypothesis

The male singing voice through puberty undergoes many changes that present challenges for the singer and choral director. The purpose of this study was to discuss the endoscopic findings seen in prepubescent choir singers.

Study Design

Single‐institution prospective study.

Methods

Subjects were recruited from the Cincinnati Boychoir and were described as Cooksey stage unchanged or mid‐voice I, as described by the Boychoir artistic director. Vocal history was obtained via questionnaire at the initial visit. Subjects with known laryngeal pathologies were excluded. Endoscopic laryngeal examinations were performed using videoendoscopy. During examination, each subject sang four discrete frequencies. Findings of the endoscopic exam were judged by a board‐certified pediatric otolaryngologist specializing in pediatric voice.

Results

We evaluated 28 subjects prior to vocal maturation. Their age range was 8 to 13 years old (mean = 10.2 ± 1.2 years). The singing voice category of all 28 subjects was described as soprano vocal range by the Boychoir artistic director. The subjects had a mean of 1.7 ± 1.1 years in the Boychoir (0–5 years). None reported history of vocal issues or voice problems in the past; seven (25%) subjects had vocal fold lesions seen at one or more frequencies; 24 (85%) subjects had a posterior gap seen at one or more frequencies. Two subjects (7%) had a posterior gap at one frequency, C3 and G3, respectively. Five subjects (18%) had a posterior gap at two frequencies, seven subjects (25%) at three frequencies, and 10 subjects (36%) in all four frequencies.

Conclusions

Our study aimed to describe the laryngeal examination of dedicated Boychoir singers prior to undergoing pubertal development and vocal maturation. In elite pediatric singers we found that vocal nodules are common (25%) and are not correlated with vocal symptoms. These findings may suggest that asymptomatic lesions may be more prevalent than previously thought. In these individuals, posterior glottic gap is common and can be considered a normal glottal configuration.

Level of Evidence

4 Laryngoscope, 131:592–597, 2021
Reforming science publishing
Authors: Moustafa Khaled
Published: June 2020

Key points

Peer review remains problematic, but only partial resolutions to the problems have been identified.

The article processing charge financial model looks like a farmer who works hard to produce food but then must pay to sell his final products to consumers.

Article categories are largely meaningless – ‘original articles’ are not the only original content, and how rapid are rapid communications?

Word limits belong to the print environment and are overly proscriptive in the digital environment.

Why is only one author identified as the corresponding author when all authors should take responsibility for their articles?
The value of narrowband imaging using the Ni classification in the diagnosis of laryngeal cancer
Authors: Ahmadzada Sejad , Tseros Evan , Sritharan Niranjan , Singh Narinder , Smith Mark , Palme Carsten E. , Riffat Faruque
Published: June 2020

Introduction

Narrowband imaging (NBI) is a special endoscopic optical enhancement setting allowing better visualization of mucosal microvasculature compared to white light endoscopy. This study evaluates the validity of NBI using the Ni classification in the detection and differentiation of severe dysplasia (SD) and glottic squamous cell carcinoma (SCC).

Methods

Patients with suspicious vocal cord lesions underwent conventional white light endoscopy followed by clinically indicated biopsy. At the same time, NBI images were obtained and graded independently. Lesions were graded from I to V according to the Ni classification and compared to histopathological findings.

Results

Fifty‐two patients were included in this study (40 SCC and 12 SD). The sensitivity and specificity of NBI in diagnosing laryngeal cancer was 95.0% (CI, 83.9%‐99.4%) and 83.3% (CI, 51.6%‐97.9%), respectively. The negative likelihood ratio was 0.06. Higher Ni grades correlated very strongly with more advanced disease.

Conclusions

NBI using the Ni classification is a sensitive diagnostic tool for the detection and differentiation of early neoplastic and preneoplastic glottic lesions. As higher Ni classification correlates strongly with advanced disease, it serves as a useful adjunct to white light endoscopy in the diagnosis of laryngeal cancer.

Level of Evidence: Level IV.
Reproducing the virus‐to‐copepod link in Arctic mesocosms using host fitness optimization
Authors: Thingstad T. Frede , Våge Selina , Bratbak Gunnar , Egge Jorun , Larsen Aud , Nejstgaard Jens Christian , Sandaa Ruth‐Anne
Published: June 2020

By shunting material out of the predatory pathway toward detritus and dissolved material, viruses are believed to have an important impact on biogeochemical functions of the pelagic microbial food web. To include viruses as a single plankton functional type (PFT) in dynamic food web models is, however, not trivial since they will then compete with predators for the same host/prey community as a shared limiting resource. As recently shown, one can solve this problem by introducing adaptation in the defensive and competitive traits of the host (prey) community. We here show how this can reproduce central aspects of viral dynamics as observed in a set of Arctic mesocosm experiments. In these experiments, contrasting microbial trophodynamics have previously been linked to the trophic cascades generated by seasonal vertical migration of large Arctic copepods. This approach thus produces a quantitative theory for the mechanisms regulating virus‐to‐prokaryote and lysis‐to‐predation ratios, and integrates this with a central role of predator top‐down control in pelagic microbial food webs.
Electrochemical corrosion behavior of LDX 2101® duplex stainless steel in a fluoride‐containing environment
Authors: Rosalbino Francesco , Scavino Giorgio , Ubertalli Graziano
Published: June 2020

The effect of fluoride on the electrochemical corrosion behavior of an LDX 2101® duplex stainless steel (DSS) was studied. Open‐circuit potential (EOC) and electrochemical impedance spectroscopy (EIS) measurements were carried out in artificial saliva and with the addition of fluoride (1 wt% NaF). The electrochemical corrosion behavior of the AISI 316L austenitic stainless steel (SS) was also evaluated for comparison. Both open‐circuit potential and EIS results indicate that DSS and austenitic SS undergo spontaneous passivation due to spontaneously formed oxide film passivating the metallic surface, in the simulated aggressive environments. However, LDX 2101® exhibits superior corrosion resistance as compared with AISI 316L, and this improvement is ascribed to the formation of a passive film which shows a higher protective effect than the one formed on AISI 316L.
Development of a standardized Gram stain procedure for bacteria and inflammatory cells using an automated staining instrument
Authors: Li Hui , Li Lele , Chi Yuanyuan , Tian Qingwu , Zhou Tingting , Han Chunhua , Zhu Yuanqi , Zhou Yusun
Published: June 2020

Gram stain is a subjective and poorly controlled test, and the resultant errors often perplex laboratory scientists. To reduce errors and make Gram stain a precisely controllable and meritorious test, a standardized Gram stain procedure for bacteria and inflammatory cells was developed using an automated staining instrument in this study. Freshly expectorated sputum specimens, used as the optimized targets, were smeared on slides by laboratory technicians, defining each slide loaded with uniform matrix and monolayer cell. And then, the staining and decolorizing time, as well as the stain and decolorant volume, were optimized as 15, 105, 1, and 25 s and 1.1, 1.4, 0.3, and 0.7 ml, respectively. Culture‐positive blood specimens and original purulent fluids were used for confirming the developed standardized Gram stain procedure. Distinct tinctures of bacteria and inflammatory cells adhered to slide uniformly in a monolayer were observed, and the obtained staining results of these samples were highly consistent with their cultured results. Furthermore, according to the staining results under different staining conditions, an updated molecular mechanism of Gram stain for bacteria and the probable staining mechanism for inflammatory cells were also proposed in this study.
A Complex Hyperkinetic Movement Disorder Responsive to Immunotherapy in a Patient with Neuromyelitis Optica
Authors: Aguiar Rafaela F. , Nóbrega Paulo R. , Veras Samuel Ranieri O. , Maia Fernanda M. , Sobreira‐Neto Manoel A. , Braga‐Neto Pedro
Published: June 2020

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Recent updates on the resistance mechanisms to epidermal growth factor receptor tyrosine kinase inhibitors and resistance reversion strategies in lung cancer
Authors: Tripathi Surya K. , Pandey Kamal , Rengasamy Kannan R. R. , Biswal Bijesh K.
Published: June 2020

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have led to a substantial improvement in the prognosis of lung cancer patients by explicitly targeting the activating mutations within the EGFR. Initially, patients harboring tumors with EGFR mutations show progression‐free survival and improvement in the response rates toward all‐generation EGFR‐TKIs; however, these agents fail to deliver the intended results in the long‐term due to drug resistance. Therefore, it is necessary to recognize specific cardinal mechanisms that regulate the resistance phenomenon. Understanding the intricate mechanisms underlying EGFR‐TKIs resistance in lung cancer could provide cognizance for more advanced targeted therapeutics. The present review features insights into current updates on the discrete mechanisms, including secondary or tertiary mutations, parallel and downstream signaling pathways, acquiring an epithelial‐to‐mesenchymal transition (EMT) signature, microRNAs (miRNAs), and epigenetic alterations, which lead to intrinsic and acquired resistance against EGFR‐TKIs in lung cancer. In addition, this paper also reviews current possible strategies to overcome this issue using combination treatment of recently developed MET inhibitors, allosteric inhibitors or immunotherapies, transformation of EMT, targeting miRNAs, and epigenetic alterations in intrinsic and acquired EGFR‐TKIs resistant lung cancer. In conclusion, multiple factors are responsible for intrinsic and acquired resistance to EGFR‐TKIs and understanding of the detailed molecular mechanisms, and recent advancements in pharmacological studies are needed to develop new strategies to overcome intrinsic and acquired EGFR‐TKIs resistance in lung cancer.
Diagnostic utility of integrated analysis of exome and transcriptome: Successful diagnosis of Au‐Kline syndrome in a patient with submucous cleft palate, scaphocephaly, and intellectual disabilities
Authors: Yamada Mamiko , Shiraishi Yuichi , Uehara Tomoko , Suzuki Hisato , Takenouchi Toshiki , Abe‐Hatano Chihiro , Kurosawa Kenji , Kosaki Kenjiro
Published: June 2020

Background

A weakness of exome analysis lies in inability to characterize aberrant splicing other than those involving consensus donor‐acceptor sequence. To overcome this limitation, we developed a novel analytic method SAVNet that combines transcriptome and exome analysis which enabled the successful detection of carriers of splicing variants in the disease‐causing genes of autosomal recessive disorders within a normal cohort. However, the clinical utility of the SAVNet analysis in delineating splicing defects in patients without a diagnosis has yet to be documented.

Method

We performed SAVNet analysis using the integrated analysis of exome and transcriptome analysis from the peripheral blood of the patient. The patient is an undiagnosed Japanese female patient with submucous cleft palate, scaphocephaly and intellectual disability with no words at 8 years of age. Dysmorphic features included a long face, a short palpebral fissure, thick lips with an open month, premaxillary hypoplasia, a depressed nasal bridge, and satyr ears.

Result

A SAVNet analysis showed that a heterozygous intronic variant located at the −10 position of exon 5 of the HNRNPK gene on chromosome 9 created a new splice acceptor sequence “ag” and led to the incorporation of 9 intronic nucleotides into the coding sequence. The mutant protein would have three extra amino acid residues, Leu‐Leu‐Gln, inserted within the critical KH domain. The patient was diagnosed as having recently delineated Au–Kline syndrome, which is characterized by cleft palate, craniosynostosis, and intellectual disability.

Conclusion

The successful molecular diagnosis of the presently reported patient illustrates the diagnostic utility of the SAVNet analysis as an innovative way of implementing an integrated exome‐transcriptome analysis in clinical settings.
Systematic summarization of the expression profiles and prognostic roles of the dishevelled gene family in hepatocellular carcinoma
Authors: Mei Jie , Yang Xuejing , Xia Dandan , Zhou Weijian , Gu Dingyi , Wang Huiyu , Liu Chaoying
Published: June 2020

Background

Dishevelled (DVL) family members are crucial to Wnt‐induced signaling transduction, and their expression is highly correlated with the progression of multiple malignant cancers. However, the expression profiles and exact prognostic values of DVLs in hepatocellular carcinoma (HCC) have not been explored until now.

Methods

The expression of DVL isoforms was assessed using the Oncomine, HCCDB and UALCAN databases. The prognostic roles of DVLs were further evaluated using the GEPIA database. The relationship between the expression of DVLs and immune infiltration of HCC was investigated using the Timer and ImmuCellAI tools. Furthermore, protein–protein interaction (PPI) networks were built and enrichment analyses were conducted.

Results

We found that the expression levels of DVL2 (OMIM accession number: 602151) and DVL3 (OMIM accession number: 601368) were upregulated in HCC tissues as revealed by the Oncomine and HCCDB databases. Additionally, the expression of DVLs tended to be associated with advanced clinical features in the UALCAN database. Prognostic analysis revealed that the expression levels of DVL1 (OMIM accession number: 601365) and DVL3 were remarkably associated with a poor prognosis in HCC patients. The results also revealed that the DVL expression level was correlated with the infiltration levels of multiple immune cells. By constructing the PPI network and enrichment analyses, the DVL1‐3 gene was identified to interact with 20 key genes and participate in several pathways.

Conclusion

In summary, DVL2 and DVL3 are highly expressed in HCC, and DVL1 and DVL3 are related to a poor prognosis, which might be used as candidate targets for targeted therapy and reliable prognostic biomarkers in HCC.
Investigation on the role of biallelic variants in VEGF‐C found in a patient affected by Milroy‐like lymphedema
Authors: Mukenge Sylvain , Jha Sawan K. , Catena Marco , Manara Elena , Leppänen Veli‐Matti , Lenti Elisa , Negrini Daniela , Bertelli Matteo , Brendolan Andrea , Jeltsch Michael , Aldrighetti Luca
Published: June 2020

Background

Milroy‐like disease is the diagnostic definition used for patients with phenotypes that resemble classic Milroy disease (MD) but are negative to genetic testing for FLT4. In this study, we aimed at performing a genetic characterization and biochemical analysis of VEGF‐C variations found in a female proband born with congenital edema consistent with Milroy‐like disease.

Methods

The proband underwent next‐generation sequencing‐based genetic testing for a panel of genes associated with known forms of hereditary lymphedema. Segregation analysis was performed on family members by direct sequencing. In vitro studies were performed to evaluate the role of a novel identified variant.

Results

Two VEGF‐C variations were found in the proband, a novel p.(Ser65Arg) and a pathogenic c.148‐3_148‐2delCA, of paternal and maternal origin, respectively. Functional characterization of the p.(Ser65Arg) variation in vitro showed alterations in VEGF‐C processing.

Conclusions

Our findings reveal an interesting case in which biallelic variants in VEGF‐C are found in a patient with Milroy‐like lymphedema. These data expand our understanding of the etiology of congenital Milroy‐like lymphedema.
Effect of Fangzhu's nanoscale surface morphology on water collection
Authors: Wang Kang‐Le
Published: June 2020

This paper suggests a fractal mathematical model for Fangzhu's water collection by taking into account its nanoscale surface morphology. A fractal variational principle is established by the semi‐inverse method, which elucidates the conservation laws in the fractal space. Additionally, the variational formulation can also reveal the structure of the solution. An approximate analytical solution is obtained via the two‐scale transform method and He's frequency formula. Some special cases of the model are discussed numerically, showing the method is remarkably simple and capable to solve nonlinear oscillators with fractal derivatives.
Fractional heat conduction model with phase lags for a half‐space with thermal conductivity and temperature dependent
Authors: Abo‐Dahab S.M. , Abouelregal Ahmed E. , Ahmad Hijaz
Published: June 2020

In the current investigation, the thermoelasticity with a model of fractional order is used to discuss a problem of thermoelastic half‐space. Such theory depends on the time‐fractional derivative of Caputo of order α. The thermal conductivity is considered to be a variable, and the medium surface is subjected to a free from traction and a thermal shock. Then, the transform of Laplace has been utilized for the solutions of the governing equations. The inverse of the Laplace transform entertained numerically, employing a technique based on methods of Fourier expansion. The obtained numerical solutions for different variables and the obtained results are offered graphically. The effect of the variation of thermal conductivity as well as a fractional‐order parameter on displacement, temperature, and stress are studied. A comparison is made between the results obtained in the current investigation and the previous results by others when the new parameters neglect. The results obtained indicated to the significant role of the heat conduction fractional model, thermal conductivity, temperature dependent, and thermal relaxation time on the thermoelastic half‐space.
On the structure of solutions of Volterra interval‐valued integro‐differential equations
Authors: Younus Awais , Shaheen Tahira , Tunç Cemil
Published: June 2020

In this paper, we discuss the structure of the solutions for linear interval‐valued Volterra integro‐differential equations (VIDEs) based on gH‐difference. The considered VIDEs consist of six forms. Among those six forms, three forms are obtained by using the definition of generalized Hukuhara difference (or gH‐difference). We obtain solutions of that linear interval‐valued VIDEs and discuss their properties. Some examples illustrate the theory.
Preoperative computed tomography‐guided disease‐free survival prediction in gastric cancer: a multicenter radiomics study
Authors: Wang Siwen , Feng Caizhen , Dong Di , Li Hailin , Zhou Jing , Ye Yingjiang , Liu Zaiyi , Tian Jie , Wang Yi
Published: June 2020

Purpose

Preoperative and noninvasive prognosis evaluation remains challenging for gastric cancer. Novel preoperative prognostic biomarkers should be investigated. This study aimed to develop multidetector‐row computed tomography (MDCT)‐guided prognostic models to direct follow‐up strategy and improve prognosis.

Methods

A retrospective dataset of 353 gastric cancer patients were enrolled from two centers and allocated to three cohorts: training cohort (n = 166), internal validation cohort (n = 83), and external validation cohort (n = 104). Quantitative radiomic features were extracted from MDCT images. The least absolute shrinkage and selection operator penalized Cox regression was adopted to construct a radiomic signature. A radiomic nomogram was established by integrating the radiomic signature and significant clinical risk factors. We also built a preoperative tumor‐node‐metastasis staging model for comparison. All models were evaluated considering the abilities of risk stratification, discrimination, calibration, and clinical use.

Results

In the two validation cohorts, the established four‐feature radiomic signature showed robust risk stratification power (P = 0.0260 and 0.0003, log‐rank test). The radiomic nomogram incorporated radiomic signature, extramural vessel invasion, clinical T stage, and clinical N stage, outperforming all the other models (concordance index = 0.720 and 0.727) with good calibration and decision benefits. Also, the 2‐yr disease‐free survival (DFS) prediction was most effective (time‐dependent area under curve = 0.771 and 0.765). Moreover, subgroup analysis indicated that the radiomic signature was more sensitive in risk stratifying patients with advanced clinical T/N stage.

Conclusions

The proposed MDCT‐guided radiomic signature was verified as a prognostic factor for gastric cancer. The radiomic nomogram was a noninvasive auxiliary model for preoperative individualized DFS prediction, holding potential in promoting treatment strategy and clinical prognosis.
Classification of digital pathological images of non‐Hodgkin's lymphoma subtypes based on the fusion of transfer learning and principal component analysis
Authors: Zhang Jianfei , Cui Wensheng , Guo Xiaoyan , Wang Bo , Wang Zhen
Published: June 2020

Purpose

Non‐Hodgkin's lymphoma (NHL) is a serious malignant disease. Delayed diagnosis will cause anemia, increased intracranial pressure, organ failure, and even lead to death. The current main trend in this area is to use deep learning (DL) for disease diagnosis. Extracting classification information from the digital pathology images by DL may realize the automated qualitative and quantitative analysis of NHL. Previously, DL has been used to classify NHL digital pathology images with some success. However, shortcomings still exist in the data preprocessing methods and feature extraction. Therefore, this paper presents a method for the classification of NHL subtypes based on the fusion of transfer learning (TL) and principal component analysis (PCA).

Methods

First, the NHL digital pathology images were preprocessed by image division and segmentation and then input into the transfer models for fine‐tuning and feature extraction. Second, PCA was used to map the extracted features. Finally, a neural network was used as a classifier to classify the mapped features. During the fine‐tuning of the transfer models, two methods, freezing all feature extraction layers and fine‐tuning all layers, were employed to select the optimal model with the best classification result among all the preselected transfer models. On this basis, the use of freezing the layers' location was discussed and analyzed.

Results

The results show that the proposed method achieved average fivefold cross‐validation accuracies of 100%, 99.73%, and 99.20% for chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL) tumor, and each category has standard deviations 0.00, 0.53, and 0.65, respectively, in the NHL reference dataset. The overall classification accuracy for fivefold cross‐validation is 98.93%, which is an increase of 1.26% compared to the latest reported methods, having a lower standard deviation (1.00).

Conclusion

The method proposed in this paper achieves a high classification accuracy and strong model generalization for the classification of NHL, which makes it possible to conduct intelligent classification of NHL in clinical practice. Our proposed method has definite clinical value and research significance.
Diabetic neuropathies
Authors: Patel Kamakshi , Horak Holli , Tiryaki Ezgi
Published: June 2020

Diabetic neuropathies are the most common type of neuropathies seen in clinical practice. These neuropathies can range clinically from asymptomatic to manifesting symptoms caused by motor, sensory, and autonomic nerve dysfunction. These neuropathies can affect the peripheral nervous system, pain receptors, cardiovascular, urogenital, and gastrointestinal systems. This monograph presents an overview of the different types of diabetic neuropathies, their presentations, diagnostic tools, and strategies for management.
Impact of the COVID‐19 Pandemic on Unhealthy Eating in Populations with Obesity
Authors: Ashby Nathaniel J. S.
Published: June 2020

Objective

This study aimed to examine the impact of the coronavirus disease (COVID‐19) pandemic on patronage to unhealthy eating establishments in populations with obesity.

Methods

Anonymized movement data accounting for roughly 10% of devices in the United States at 138,989 unhealthy eating locations from December 1, 2019, through April 2020 and the percentage of adults with obesity, the poverty rate, and the food environment index in 65% of United States counties were collected and merged. A cluster corrected Poisson spline regression was performed predicting patronage by day, the percentage of adults with obesity in the establishment’s county, the county’s poverty rate, and its food environment index, as well as their interactions.

Results

Patronage to unhealthy eating establishments was higher where there was a higher percentage of the adult population with obesity. A similar pattern was observed for counties with a lower food environment index. These disparities appear to have increased as the COVID‐19 pandemic spread.

Conclusions

These results suggest unhealthy eating patterns during the COVID‐19 pandemic are higher in already at‐risk populations. Policy makers can use these findings to motivate interventions and programs aimed at increasing healthy food intake in at‐risk communities during crises.
Impact of insurance type and timing of Medicaid enrollment on survival among adolescents and young adults with cancer
Authors: Parsons Helen M. , Maguire Frances B. , Morris Cyllene R. , Parikh‐Patel Arti , Brunson Ann M. , Wun Ted , Keegan Theresa H.M.
Published: June 2020

Background

Adolescents and young adults (AYAs) with public or no insurance experience later stage at diagnosis and worse overall survival compared with those with private insurance. However, prior studies have not distinguished the survival impact of continuous Medicaid coverage prior to diagnosis compared with gaining Medicaid coverage at diagnosis.

Methods

We linked a cohort of AYAs aged 15‐39 who were diagnosed with 13 common cancers from 2005 to 2014 in the California Cancer Registry with California Medicaid enrollment files to ascertain Medicaid enrollment, with other insurance determined from registry data. We used Cox proportional hazards regression to evaluate the impact of insurance on survival, adjusting for clinical and demographic characteristics.

Results

Among 62 218 AYAs, over 65% had private/military insurance, 10% received Medicaid at diagnosis, 13.2% had continuous Medicaid, 4.1% had discontinuous Medicaid, 1.7% had other public insurance, 3% were uninsured, and 2.6% had unknown insurance. Compared with those with private/military insurance, individuals with Medicaid insurance had significantly worse survival regardless of when coverage began (received Medicaid at diagnosis: hazard ratio [95% confidence interval]: 1.51 [1.42‐1.61]; continuously Medicaid insured: 1.42 [1.33‐1.52]; discontinuous Medicaid: 1.64 [1.49, 1.80]). Analyses of those with Medicaid insurance only demonstrated slightly worse cancer‐specific survival among those with discontinuous Medicaid or enrollment at diagnosis compared with those with continuous enrollment, but results were not significant stratified by cancer site.

Conclusions and relevance

AYAs with Medicaid insurance experience worse cancer‐specific survival compared with those with private/military insurance, yet continuous enrollment demonstrates slight survival improvements, providing potential opportunities for future policy intervention.
Radical cyclopolymerization of dimethacrylates bearing rigid adamantane‐like core derived from naturally occurring myo‐inositol
Authors: Sudo Atsushi , Nishiyama Kyohei , Morimoto Mika , Yamamoto Shinichiro
Published: June 2020

Dimethacrylates with rigid adamantane‐like cores were synthesized from myo‐inositol orthoester via a sequence of (a) acylation or silylation of the equatorially oriented hydroxyl group, followed by (b) attachment of methacrylate groups on the axially oriented hydroxyl groups. The radical homopolymerization of these compounds proceeded via cyclopolymerization without crosslinking, as the two axially oriented methacrylate groups were fixed in close proximity with each other. The dimethacrylates underwent radical copolymerization with methyl methacrylate (MMA) to afford the corresponding polymethacrylates, exhibiting high glass transition temperatures (Tg), due to the introduction of the rigid orthoester moieties originating from the monomers and the macrocyclic structures formed via intramolecular cyclization of the two methacrylate groups of the monomers. The polymers obtained by polymerization of the dimethacrylate bearing a silylated hydroxyl group served as precursors of hydroxyl‐bearing polymers, which also exhibited high Tg due to the formation of a hydrogen bonding network between the hydroxyl groups.