bluuebunny/crossref_metadata_2025 huggingface dataset:
Rectal cancer lateral pelvic sidewall lymph nodes: a review of controversies and management
Authors: Williamson J S , Quyn A J , Sagar P M
Published: August 2020

Background

The management of lateral pelvic lymphadenopathy in low rectal cancer poses an oncological and technical challenge. Interpretation of the literature is confounded by different approaches to management in the East and West, and a lack of randomized data from which to draw accurate conclusions regarding the optimal approach. Recent collaboration between Eastern and Western centres has increased the standardization of care. Despite this, significant differences in international guidelines remain. The aim of this review was to appraise the available literature and propose a management algorithm.

Methods

A literature review of all relevant studies was performed to summarize the historical evidence, as well as establish the significance of clinically positive lateral pelvic sidewall nodes, and the role of neoadjuvant chemoradiotherapy and lateral pelvic node dissection. A management algorithm was developed based on this review of the literature.

Results

The management of pelvic sidewall lymphadenopathy in rectal cancer is non-standardized, with geographical differences. The mechanism of lateral lymphatic spread is well defined; the risk increases with lower tumour height and advanced T category. Existing data indicate that acceptable disease-free and overall survival can be achieved by neoadjuvant chemoradiotherapy with selective lateral pelvic node dissection.

Conclusion

Suspicious lateral pelvic sidewall nodes, particularly in the internal iliac chain, should be considered as resectable locoregional disease, and surgery offered for enlarged nodes that do not respond to neoadjuvant chemoradiotherapy.
A novel bilayered expanded polytetrafluoroethylene glaucoma implant creates a permeable thin capsule independent of aqueous humor exposure
Authors: Bicket Amanda Kiely , Szeto Julia , Roeber Peter , Towler Jeff , Troutman Mitch , Craven E. Randy , Khatana Anup , Ahmed Ike , Quigley Harry , Ramulu Pradeep , Pitha Ian F.
Published: August 2020

The purpose of these studies was to evaluate clinical, functional, and histopathological features of glaucoma drainage implants (GDIs) fabricated from novel, custom‐tailored expanded polytetrafluoroethylene (ePTFE). Implants of matching footprints were fabricated from silicone (Control) and novel, bilayered ePTFE. ePTFE implants included: (a) one that inflated with aqueous humor (AH) (High), (b) one that inflated with a lower profile (Low), (c) an uninflated implant not connected to the anterior chamber (Flat), and (d) one filled with material that did not allow AH flow (Filled). All implants were placed in adult New Zealand White rabbits and followed over 1–3 months with clinical exams and intraocular pressure. The permeability of tissue capsules surrounding GDIs was assessed using constant‐flow perfusion with fluoresceinated saline at physiologic flow rates. After sacrifice, quantitative histopathological measures of capsule thickness were compared among devices, along with qualitative assessment of cellular infiltration and inflammation. Capsular thickness was significantly reduced in blebs over ePTFE (61.4 ± 53 μm) versus silicone implants (193.6 ± 53 μm, p = .0086). AH exposure did not significantly alter capsular thickness, as there was no significant difference between High and Filled (50.9 ± 29, p = .34) implants. Capsules around ePTFE implants demonstrated permeability with steady‐state pressure: flow relationships at physiologic flow rates and rapid pressure decay with flow cessation, while pressure in control blebs increased even at low flow rates and showed little decay. Perfused fluorescein dye appeared beyond the plate border only in ePTFE implants. ePTFE implants are associated with thinner, more permeable capsules compared to silicone implants simulating presently used devices.
Surgical Considerations and Decision Making in Surgically Facilitated Orthodontic Treatment/Periodontally Accelerated Osteogenic Orthodontics
Authors: Mandelaris George A. , Richman Colin , Kao Richard T.
Published: August 2020

Focused Clinical Question

Surgically facilitated orthodontic treatment (SFOT)/periodontally accelerated osteogenic orthodontics (PAOO) has the potential of allowing safer orthodontic treatment in vulnerable periodontium with thin phenotypes. SFOT/PAOO is a phenotype modification therapy (PhMT) approach where thin bone morphotype and/or gingiva are surgically augmented to convert a fragile‐thin to a robust‐thick periodontal environment. This permits orthodontic treatment in these previously thin phenotype cases to proceed without iatrogenically‐induced adverse effects. This is an infrequently performed procedure with few available clinical recommendations.

In this practical application paper, three clinicians with the collective clinical experience of over 1500 SFOT cases developed a clinical decision‐making algorithm outlining the key steps for SFOT. A sample case is provided for clinical appreciation of the procedure. Lastly, this panel reviewed and detailed the critical decision making and surgical approaches associated with the use of SFOT. Though the basic decision making is consistent, individual variations on surgical management are compared. This is summarized in a clinical decision tree along with a sample clinical case. Additionally, the cumulative experience has been organized into tables that provide comparative decision and surgical approaches. There are similarities and differences. Lastly, strategies that have not been individually effective are also noted.

Conclusion

SFOT/PAOO is an effective PhMT approach whereby the bone and/or soft tissue phenotype can be surgically modified to permit orthodontic treatment in patients with thin phenotypes. The cumulative experience of three experienced clinicians provides clinical recommendations for SFOT management of PhMT for pre‐orthodontic treatment.
What's happening in carotid stent? A case report of prominent plaque protrusion after carotid artery stenting observed on angioscopy
Authors: Enomoto Yukiko , Egashira Yusuke , Iwama Toru
Published: August 2020

Thromboembolic complications after carotid artery stenting (CAS) remain an unsolved problem, and several intravascular imaging tools have been proposed to clarify the mechanism of these complications. We report a case of intraprocedural plaque protrusion revealed by angioscopy. A 64‐year‐old woman underwent CAS for left carotid artery stenosis. After stent placement, optical frequency domain imaging demonstrated some plaque protrusion, and angioscopy showed prominent mobile plaque fragments protruding into the vessel between stent struts and confirmed the coverage of the protruded plaque after the overlapping stent was placed. Compared with other tools, angioscopy more clearly revealed plaque protrusion in the vessel after CAS.
Immune Thrombocytopenic Purpura, a rare manifestation of active tuberculosis: Case report
Authors: Fajardo Yadhira A. , Morales Eliana I. , Sua Luz F. , Fernández‐Trujillo Liliana
Published: August 2020

Tuberculosis is currently considered a public health issue worldwide. Although a large number of hematological disorders related to tuberculosis have been described, immune thrombocytopenic purpura in patients with active tuberculosis is very rare but must be considered in a patient with no other evident cause.
Tubulointerstitial nephritis and uveitis syndrome with concurrent macular edema caused by granulomatous uveitis
Authors: Nishi Tomomi , Tamura Hiroshi , Miyashita Yusuke , Nakazato Hitoshi
Published: August 2020

It is difficult to differentiate between TINU syndrome and sarcoidosis in young people with renal abnormalities and ocular lesions. Since the spontaneous prognosis of interstitial nephritis is different between the two, it was considered necessary to actively conduct tests for differentiation.
Preoperative soluble VCAM‐1 contributes to predict late mortality after coronary artery surgery
Authors: Corbalan Ramon , Garcia Mauricio , Garrido‐Olivares Luis , Garcia Lorena , Perez Gonzalo , Mellado Rosemarie , Zalaquett Ricardo , Chiong Mario , Quitral Jorge , Lavandero Sergio
Published: August 2020

Background

Soluble vascular cell adhesion molecule‐1 has been associated with long‐term cardiovascular mortality in patients with stable coronary artery disease and to the development of new atrial fibrillation in subjects with cardiovascular risk factors but no evidence of cardiac disease.

Hypothesis

Preoperative soluble vascular cell adhesion molecule‐1 predicts the risk of future all‐cause death and cardiovascular death among patients submitted to elective coronary artery bypass surgery.

Methods

From a cohort of 312 patients who underwent elective coronary artery bypass surgery prospectively followed for a median of 6.7 years, we evaluated the prognostic role of preoperative soluble vascular cell adhesion molecule‐1, inflammatory markers, CHA2DS2‐VASc score and development of postoperative atrial fibrillation (POAF). Univariable and multivariable Cox regression analyses were performed to establish an association of these parameters with long term all‐cause death and cardiovascular death.

Results

During 2112 person‐years of follow‐up, we observed 41 deaths, 10 were cardiovascular deaths. Independently increased levels of preoperative soluble vascular cell adhesion molecule‐1, POAF, and CHA2DS2‐VASc score were associated with all‐cause mortality. After multivariate adjustment, elevated preoperative soluble vascular cell adhesion molecule‐1 and POAF were the only independent predictors of all‐cause death. Also, preoperative soluble vascular cell adhesion molecule‐1, POAF, and CHA2DS2‐VASc score resulted in being independent predictors of cardiovascular mortality.

Conclusions

Increased circulating levels of preoperative soluble vascular cell adhesion molecule‐1, together with POAF and CHA2DS2‐VASc score, were significantly associated with future all‐cause death and cardiovascular death among patients submitted to coronary artery bypass surgery.
Passages of cancer caregivers' unmet needs across 8 years
Authors: Kim Youngmee , Carver Charles S. , Ting Amanda , Cannady Rachel S.
Published: August 2020

Background

Identifying and addressing caregivers' unmet needs have been suggested as a way of reducing their distress and improving their quality of life. However, the needs of family cancer caregivers are complex in the period of long‐term survivorship in particular because they may diverge as the patients' survivorship trajectory does, and that is what this study investigated.

Methods

Family cancer caregivers completed prospective, longitudinal surveys 2, 5, and 8 years after diagnosis (n = 633). Early caregiving characteristics and demographics were measured at 2 years. Caregiver status (former caregivers–remission, current caregivers, and bereaved caregivers) and unmet needs were measured at 3 assessments.

Results

Caregivers' unmet needs at 8 years were attributable to the passages of the caregiving status as their patients' illness trajectory diverged from the initial state of receiving care. Specifically, either prolonged caregiving or having a break from caregiving followed by bereavement during long‐term survivorship was related to various domains of unmet needs at 8 years (t > 2.35, P < .02). Early perceived caregiving stress also predicted all domains of unmet needs at 8 years (t > 2.50, P < .02). Unmet needs at 8 years were the highest across the 3 assessment time points (F > 37.51, P < .001).

Conclusions

The caregiving status trajectory over 8 years was a substantial predictor of family caregivers' unmet needs at the 8‐year mark. Findings provide guidance for the development of evidence‐based programs and patient/caregiver‐centered care policies to reduce the unmet needs of family caregivers, which reflect the diverse trajectories of cancer caregivership, many years after the diagnosis of their patients.
Assessing the diagnostic accuracy for pleomorphic adenoma and Warthin tumor by employing the Milan System for Reporting Salivary Gland Cytopathology: An international, multi‐institutional study
Authors: Allison Derek B. , Smith Alexander P. , An Daniel , Miller James Adam , Shafique Khurram , Song Sharon , Viswanathan Kartik , Eykman Elizabeth , Rao Rema A. , Wiles Austin , Barkan Güliz A. , Nayar Ritu , Fadda Guido , Powers Celeste N. , Rossi Esther Diana , Siddiqui Momin T. , Ali Syed Z. , Kholová Ivana , Layfield Lester J. , Field Andrew , Baloch Zubair , Maleki Zahra
Published: August 2020

Background

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has established distinct diagnostic categories for reporting cytopathological findings, and each is associated with a defined risk of malignancy (ROM). However, the ROM is applied at the overall category level and is not specific for particular morphological entities within a category. Here, the diagnostic performance of the MSRSGC for pleomorphic adenoma (PA) and Warthin tumor (WT) is reported.

Methods

The pathology archives of 11 institutions from 4 countries were retrospectively searched to identify all salivary gland fine‐needle aspiration (FNA) biopsies with a differential or definitive diagnosis of PA or WT and all resection specimens with a diagnosis of PA or WT; only paired cases were included. All FNA diagnoses were retrospectively classified according to the MSRSGC.

Results

A total of 1250 cases met the inclusion criteria, and they included 898 PA cases and 352 WT cases. The ROM in the benign neoplasm category was 3.0% and 1.3% for cases with a differential or definitive diagnosis of PA and WT, respectively. The ROM in the salivary gland neoplasm with uncertain malignant potential (SUMP) category was 2.7% and 18.8% for PA and WT, respectively (P = .0277). The diagnostic accuracy for PA and WT was 95.1% and 96.1%, respectively.

Conclusions

The diagnostic accuracy for PA and WT on FNA is high. Furthermore, these findings highlight the difference in the ROMs associated with 2 specific differential diagnoses in the SUMP category: basaloid neoplasms and oncocytoid neoplasms.
Refining the Milan System for Reporting Salivary Gland Cytopathology
Authors: Faquin William C.
Published: August 2020

An international and multi‐institutional cohort of salivary gland fine‐needle aspiration cases has been used to investigate the diagnosis and reporting of pleomorphic adenomas and Warthin tumors in the Milan System for Reporting Salivary Gland Cytopathology. This work helps to clarify important cytological reporting aspects of these 2 common salivary gland tumors.
Evaluation of the clinical utility of maximum intensity projections of 3D contrast‐enhanced, T1‐weighted imaging for the detection of brain metastases
Authors: Hainc Nicolin , Federau Christian , Tyndall Anthony , Mittermeier Andreas , Bink Andrea , Stippich Christoph , Schubert Tilman
Published: August 2020

Background

To visualize and assess brain metastases on magnetic resonance imaging, radiologists face an ever‐increasing pressure to perform faster and more efficiently. The usage of maximum intensity projections (MIPs) of contrast‐enhanced T1‐weighed (T1ce) magnetization‐prepared rapid acquisition with gradient echo (MP‐RAGE) images proposes to increase reading efficiency by increasing lesion conspicuity while reducing in the number of images to be reviewed.

Aim

To assess if MIPs save reading time and achieve the same level of diagnostic accuracy as standard 1 mm T1ce images for the detection of brain metastases.

Methods

Forty‐four patients were included in this retrospective study. Axial reformations of T1ce MP‐RAGE (TR/TE = 2300/2.25 ms, resolution = 1 mm3) images were analyzed and post‐processed into 5 and 10 mm MIPs. Two readers evaluated the randomly assorted images and recorded reading time. Reading time differences were analyzed using the Wilcoxon test, and inter‐reader statistics were performed using Bland–Altman plots.

Results

About 22.5 61.2 s/study and 43.8 ± 159.9 s/study were saved using 5 and 10 mm MIPs, respectively. Combined average sensitivity was 92.0% for 5 mm MIPs and 86.3% for 10 mm MIPs compared to standard 1 mm axial slices, with an average rate of 0.98 and 0.57 false positives per study, respectively

Conclusion

While 5 mm and 10 mm T1ce MP‐RAGE MIPs showed a clinical benefit in reducing reading times for evaluation of brain metastases, they should be used in conjunction with standard 1 mm images for best sensitivity and specificity, a practice which possibly annuls their benefit.
Pharmacokinetics and Bioequivalence Estimation of Two Formulations of Alfuzosin Extended‐Release Tablets
Authors: Al Bawab Abdel Qader , Alkhalidi Bashar A. , Albarahmieh Esra'a , Qassim Sami M.A. , Al‐Saifi Mohammad A.D. , Al‐Saifi Bashar , Ling Jonathan , Al‐Qerem Walid
Published: August 2020

Alfuzosin is a medication approved by the US Food and Drug Administration to treat benign prostatic hyperplasia symptoms. Bioequivalence studies are demanded by regulatory authorities to evaluate the expected in vivo biological similarity of 2 formulations of a medication. The aim of this study is to assess the bioavailability of the generic (test) and branded (reference) formulations of 10‐mg alfuzosin extended‐release tablets after oral administration to healthy adults under fed conditions. The study used a comparative randomized, single‐dose, 2‐way crossover open‐label study design. Thirty‐three participants were recruited and completed the clinical assessment. The pharmacokinetic parameters maximum plasma concentration (Cmax), area under the plasma concentration–time curve (AUC0‐t), AUC extrapolated to infinity (AUC0‐∞), time to maximum concentration, and elimination half‐life were estimated to prove bioequivalence. The confidence intervals for the log‐transformed test/reference ratios for alfuzosin 110.7% (98.0–124.9) and 112.0% (101.9–123.1) for Cmax and AUC0‐t respectively, which are within the allowed limits specified by the regulatory authorities (80–125% for Cmax and AUC0‐t). The test formulation can therefore be prescribed as an alternative to the reference for symptomatic treatment of benign prostatic hyperplasia.
Pharmacokinetics and Bioequivalence of 2 Immediate‐Release Tofacitinib Tablet Formulations in Chinese Healthy Volunteers Under Fasting and Fed Conditions
Authors: Li Xin , Liu Lihua , Deng Yang , Li Yuan , Zhang Ping , Wang Yangyang , Xu Bing , Feng Jie , Huang Lu
Published: August 2020

The purpose of this study was to evaluate the bioequivalence of a generic immediate‐release tofacitinib tablet versus a brand‐named immediate‐release tofacitinib tablet under fasting and fed conditions, and the food effect on pharmacokinetic profiles of the both formulations. This randomized, open‐label, 2‐period, crossover, bioequivalence study included 52 healthy Chinese subjects (fasting cohort: n = 26; fed cohort: n = 26). The subjects were assigned to receive a single 5‐mg dose of generic or brand‐named tofacitinib. Blood samples were collected at predosing and up to 14 hours after dosing. Tofacitinib concentrations in plasma were analyzed by high‐performance liquid chromatography–tandem mass spectrometry. Safety was monitored. There were no significant differences in maximum plasma concentration, area under the plasma concentration–time curve from time zero to time t (AUC0‐t), AUC from time zero to infinity (AUC0‐∞), and terminal elimination half‐life between the test and reference formulations (all P > .05); high‐fat food had no significant effect on AUC0‐t, AUC0‐∞, or terminal elimination half‐life of immediate‐release tofacitinib tablets (all P > .05). The 90% confidence intervals of the test/reference ratios of log‐transformed maximum plasma concentration, AUC0‐t, and AUC0‐∞ were within the range of 80% to 125% under both fasting and fed conditions. No serious adverse events were reported. The 2 formulations of immediate‐release tofacitinib tablets are bioequivalent and well tolerated under both fasting and fed conditions in healthy Chinese volunteers. Food had no clinically relevant effects on drug exposure of tofacitinib.
Graphic process units‐based chicken swarm optimization algorithm for function optimization problems
Authors: Lin Min , Zhong Yiwen , Chen Riqing
Published: August 2020

This article focuses on how to design an efficient GPU‐based chicken swarm optimization (CSO) algorithm (GCSO), so as to improve diversity and speed up convergence by running a large number of populations in parallel. GCSO mainly improves the sequential CSO in three aspects: (i) GCSO modifies the location updating equation of the rooster and proposes a parallel iterative strategy to transform the sequential iteration process into a parallel iterative process, thereby achieving fine‐grained parallelism and improving the convergence speed. (ii) A multirange search strategy is proposed to build different neighborhoods for each flock on the graphic process units (GPU), so that each flock searched in their respective neighborhoods, thus increasing the density and diversity of the search, and making it not easy to fall into a local optimum. (iii) A new column storage structure is designed to meet the requirement of coalescent access on GPU. Twelve benchmark functions are selected to compare GCSO algorithm with some sequential intelligence optimization algorithms and the GPU‐based particle swarm algorithm. The results show that the GCSO is able to obtain a speedup up to 163.09× compared with the CSO and achieve better optimization results in terms of both optimization accuracy and convergence speed than some intelligence optimization algorithms.
Physiologically‐Based Pharmacokinetic Modeling to Predict the Clinical Efficacy of the Coadministration of Lopinavir and Ritonavir against SARS‐CoV‐2
Authors: Thakur Aarzoo , Tan Shawn Pei Feng , Chan James Chun Yip
Published: August 2020

Lopinavir/ritonavir, originally developed for treating HIV, is currently undergoing clinical studies for treating the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Although recent reports suggest that lopinavir exhibits in vitro efficacy against SARS‐CoV‐2, it is a highly protein‐bound drug and it remains unknown if it reaches adequate in vivo unbound (free) concentrations in lung tissue. We built a physiologically‐based pharmacokinetic model of lopinavir/ritonavir in white and Chinese populations. Our aim was to perform pharmacokinetic/pharmacodynamic correlations by comparing simulated free plasma and lung concentration values achieved using different dosing regimens of lopinavir/ritonavir with unbound half‐maximal effective concentration (EC50,unbound) and unbound effective concentration 90% values of lopinavir against SARS‐CoV‐2. The model was validated against multiple observed clinical datasets for single and repeated dosing of lopinavir/ritonavir. Predicted pharmacokinetic parameters, such as the maximum plasma concentration, area under the plasma concentration‐time profile, oral clearance, half‐life, and minimum plasma concentration at steady‐state were within two‐fold of clinical values for both populations. Using the current lopinavir/ritonavir regimen of 400/100 mg twice daily, lopinavir does not achieve sufficient free lung concentrations for efficacy against SARS‐CoV‐2. Although the Chinese population reaches greater plasma and lung concentrations as compared with whites, our simulations suggest that a significant dose increase from the current clinically used dosing regimen is necessary to reach the EC50,unbound value for both populations. Based on safety data, higher doses would likely lead to QT prolongation and gastrointestinal disorders (nausea, vomiting, and diarrhea), thus, any dose adjustment must be carefully weighed alongside these safety concerns.
Estimation of carrier frequency offset for FBMC/OQAM by using modified Kalman filtering
Authors: Rani S.N. Nisha , Sridevi B.
Published: August 2020

Filter bank multicarrier (FBMC) based on offset quadrature amplitude modulation (OQAM) is regarded as the prospective system for mobile communication. To utilize the potential of the system, the issues like carrier frequency offset have to be investigated extensively. The modulations in the multicarrier system draw a great interest among researchers and engineers in the telecommunication field. Despite the OFDM advantages, significant disadvantages in the system enable researches to approach into efficiently evolved FBMC system. In this paper, the detrimental effects caused by carrier frequency offset on the received signal is considered. Carrier Frequency Offset (CFO) compensation has been effectively undertaken by modified Kalman filtering. The compensation technique not only depends on the specific FBMC modification but also influenced by the selected receiver. A comprehensive analysis of the frequency offset response under three conditions (without offset, with offset, and the compensated samples) has been performed in the proposed system with performance measures as bit error rate (BER) and signal‐to‐noise ratio. 9 CFO compensation is analyzed by varying the channel characteristics (additive white Gaussian noise [AWGN] and Rayleigh Fading) and subcarrier filtering (prototype filter, Gaussian filter, and root‐raised coefficients). From the overall analysis, it is observed that the BER varies from 0.1 to 0.001.
Adaptive modulation allocation algorithm in elastic optical networks
Authors: Bandiri Sabi Y.M. , Pimenta Tales C. , Durand Fabio R. , Spadoti Danilo H.
Published: August 2020

This paper introduces a new way to allocate the modulation format and improves the energy efficiency in elastic optical networks. For every connection request, both the quality of transmission and quality of service requirements are investigated. The allocation of modulation formats is based on both the physical distance and the required number of frequency slots. To improve the energy efficiency, Yen's algorithm is executed for every connection requested, and the lightpath with the lowest power consumption is selected. Numerical results were compared with adaptive modulation algorithms presented in the existing literature. The energy efficiency was improved by up to 27%, the used bandwidth available was reduced by up to 60%, and the blocking probability was decreased by 30% using our proposed adaptive algorithm.
Codetection of pulmonary tuberculosis and toxoplasmosis in a pediatric bronchoalveolar lavage specimen: A cytologist's assistance to clinical management
Authors: Vasantham Vyshnavi , Singh Garima , Jahan Aarzoo , Gupta Ruchika , Dogra Rakesh K. , Sarin Namrata , Singh Sompal
Published: August 2020

Background

Toxoplasmosis causes serious and sometimes life‐threatening disease in immunocompromised patients like organ transplant recipients, immunodeficiency disorders or HIV‐infected individuals. The co‐occurrence of toxoplasmosis in a respiratory sample harboring tuberculosis (TB) may be missed especially in an area endemic for the latter infection.

Case report

A 10‐year‐old child presented with complaints of fever with loss of appetite and weight. Based on radiological and clinical features, a presumptive diagnosis of pulmonary TB was made and bronchoalveolar lavage (BAL) performed for cytological and microbiological confirmation. Smears from BAL showed numerous lymphocytes along with few ciliated columnar epithelial cells. Ziehl‐Neelsen stain for acid‐fast bacilli was positive. The Giemsa‐stained cytosmears also showed clusters of crescent‐shaped tachyzoites of toxoplasma gondii in a background of lymphocytes. The patient was initiated on anti‐tubercular therapy with marked clinical improvement.

Conclusion

A diligent screening of cytosmears for a possible coinfection in a TB‐positive sample is essential for the cytopathologists to detect coexisting toxoplasmosis, which is a rare but treatable disease.
Multiplatform molecular test performance in indeterminate thyroid nodules
Authors: Lupo Mark A. , Walts Ann E. , Sistrunk J. Woody , Giordano Thomas J. , Sadow Peter M. , Massoll Nicole , Campbell Ryan , Jackson Sara A. , Toney Nicole , Narick Christina M. , Kumar Gyanendra , Mireskandari Alidad , Finkelstein Sydney D. , Bose Shikha
Published: August 2020

Background

Approximately 25% of thyroid nodule fine‐needle aspirates (FNAs) have cytology that is indeterminate for malignant disease. Accurate risk stratification of these FNAs with ancillary testing would reduce unnecessary thyroid surgery.

Methods

We evaluated the performance of an ancillary multiplatform test (MPTX) that has three diagnostic categories (negative, moderate, and positive). MPTX includes the combination of a mutation panel (ThyGeNEXT®) and a microRNA risk classifier (ThyraMIR®). A blinded, multicenter study was performed using consensus histopathology diagnosis among three pathologists to validate test performance.

Results

Unanimous consensus diagnosis was reached in 197 subjects with indeterminate thyroid nodules; 36% had disease. MPTX had 95% sensitivity (95% CI,86%‐99%) and 90% specificity (95% CI,84%‐95%) for disease in prevalence adjusted nodules with Bethesda III and IV cytology. Negative MPTX results ruledout disease with 97% negative predictive value (NPV; 95% CI,91%‐99%) at a 30% disease prevalence, while positive MPTX results ruledin high risk disease with 75% positive predictive value (PPV; 95% CI,60%‐86%). Such results are expected in four out of five Bethesda III and IV nodules tested, including RAS positive nodules in which the microRNA classifier was useful in rulingin disease. 90% of mutation panel false positives were due to analytically verified RAS mutations detected in benign adenomas. Moderate MPTX results had a moderate rate of disease (39%, 95% CI,23%‐54%), primarily due to RAS mutations, wherein the possibility of disease could not be excluded.

Conclusions

Our results emphasize that decisions for surgery should not solely be based on RAS or RAS‐like mutations. MPTX informs management decisions while accounting for these challenges.
Utility of duct‐washing cytology for detection of early breast cancer in patients with pathological nipple discharge: A comparative study with fine‐needle aspiration cytology
Authors: Motoda Norio , Ohashi Ryuji , Makino Takahiro , Manabe Eriko , Makita Masujiro , Naito Zenya
Published: August 2020

Background

Pathological nipple discharge (PND) is a relatively common symptom of breast cancer affecting the nipple. Mammary ductscopy (MD) allows direct visualization of the ductal lumen and collection of a cytological specimen using duct‐washing cytology (DWC). Herein, we clarified the diagnostic efficacy of DWC for the detection of breast cancers with PND, compared with fine‐needle aspiration cytology (FNAC).

Methods

We retrospectively examined 48 patients with PND who underwent DWC by MD (ductosccopy group; histologically determined by intraductal biopsy [IDB] or surgical specimen). The results of sensitivity and specificity of DWC were compared with that of FNAC (conventional group; histologically determined by core needle biopsy). Clinicopathological factors were compared between the ductoscopy and the conventional groups.

Results

Of eight histologically malignant cases in the ductoscopy group, one case was cytologically judged as malignant and three as indeterminate. Sensitivity and specificity of DWC were 50.0% and 82.5%, respectively. Malignant cases were mostly solid papillary carcinomas (SPCs), and benign cases were intraductal papillomas (IDPs). In the conventional group, sensitivity and specificity of FNAC were 88.0% and 38.2%, respectively, and malignant cases were mainly invasive carcinomas of no special type. Tumors in the ductocsopy group had more favorable prognostic features than those in the conventional group.

Conclusion

DWC has limited diagnostic value due to the high incidence of SPC, whose cytological features are indistinguishable from IDP. As DWC alone may be unreliable, comprehensive examination with IDB and MD findings is recommended.
Epigallocatechin gallate and theaflavin gallate interaction in SARS‐CoV‐2 spike‐protein central channel with reference to the hydroxychloroquine interaction: Bioinformatics and molecular docking study
Authors: Maiti Smarajit , Banerjee Amrita
Published: August 2020

SARS‐CoV‐2 or COVID‐19 pandemic global outbreak created the most unstable situation of human health–economy. In the past two decades different parts of the word experienced smaller or bigger outbreak related to human coronaviruses. The spike glycoproteins of the COVID‐19 (similar to SARS‐CoV) attach to the angiotensin‐converting enzyme (ACE2) and transit over a stabilized open state for the viral internalization to the host cells and propagate with great efficacy. Higher rate of mutability makes this virus unpredictable/less sensitive to the protein/nucleic acid based drugs. In this emergent situation, drug‐induced destabilization of spike binding to RBD could be a good strategy. In the current study we demonstrated by bioinformatics (CASTp: computed atlas of surface topography of protein, PyMol: molecular visualization) and molecular docking (PatchDock and Autodock) experiments that tea flavonoids catechin products mainly epigallocatechin gallate or other like theaflavin gallate demonstrated higher atomic contact energy (ACE) value, binding energy, Ki value, ligand efficiency, surface area and more amino acid interactions than hydroxychloroquine (HCQ) during binding in the central channel of the spike protein. Moreover, out of three distinct binding sites (I, II and III) of spike core when HCQ binds only with site III (farthest from the nCoV‐RBD of ACE2 contact), epigallocatechin gallate and theaflavin gallate bind all three sites. As sites I and II are in closer contact with open state location and viral–host contact area, these drugs might have significant effects. Taking into account the toxicity/side effects by chloroquine/HCQ, present drugs may be important. Our laboratory is working on tea flavonoids and other phytochemicals in the protection from toxicity, DNA/mitochondrial damage, inflammation and so on. The present data might be helpful for further analysis of flavonoids in this emergent pandemic situation.
Potentiality of Q3 characterization of nanosystem: Surrogate data for obtaining a biowaiver
Authors: Mohan Vignesh , Yadav Khushwant S.
Published: August 2020

A tremendous increase in the entry of drug delivery systems (DDSs) based on nanotechnology has been observed as a result of the ability of pharmaceutical nanotechnology to overcome the various drawbacks related to the first generation DDS. The patent period of these proprietary branded drugs gives its manufacturers sole exclusivity of their product in the market. As the patent period of these products expire, the generic players will initiate their attempts to manufacture and bring generic versions of the reference listed drug product (RLD) into the market. The regulatory approval for a generic DDS based on nanotechnology requires proving the therapeutic equivalence of the generic product with that of the RLD via pharmacodynamics clinical endpoint study on healthy subjects or patients. These studies are extremely complex, expensive and time‐consuming and may have uncertain outcomes. Furthermore, development, scale‐up and manufacturing of generic versions of nanotechnology‐based DDS involves complex steps and achieving an optimized formulation heavily depends on the process parameters during manufacturing. The information in this review addresses the said issues above and emphasizes on the possibility of using exhaustive in vitro characterization of the generic versions of nanotechnology‐based DDSs in the current market to obtain a biowaiver. Various processes involved and their importance in obtaining an optimized formulation have been described to address the issue regarding manufacturing complexities.
Virulence phenotypes result from interactions between pathogen ploidy and genetic background
Authors: Feistel Dorian J. , Elmostafa Rema , Hickman Meleah A.
Published: August 2020

Studying fungal virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. However, the role of ploidy has often been overlooked when studying virulence in eukaryotic pathogens. Since fungal pathogens, including the human opportunistic pathogen Candida albicans, can display extensive ploidy variation, assessing how ploidy impacts virulence has important clinical relevance. As an opportunistic pathogen, C. albicans causes nonlethal, superficial infections in healthy individuals, but life‐threatening bloodstream infections in individuals with compromised immune function. Here, we determined how both ploidy and genetic background of C. albicans impacts virulence phenotypes in healthy and immunocompromised nematode hosts by characterizing virulence phenotypes in four near‐isogenic diploid and tetraploid pairs of strains, which included both laboratory and clinical genetic backgrounds. We found that C. albicans infections decreased host survival and negatively impacted host reproduction, and we leveraged these two measures to survey both lethal and nonlethal virulence phenotypes across the multiple C. albicans strains. In this study, we found that regardless of pathogen ploidy or genetic background, immunocompromised hosts were susceptible to fungal infection compared to healthy hosts. Furthermore, for each host context, we found a significant interaction between C. albicans genetic background and ploidy on virulence phenotypes, but no global differences between diploid and tetraploid pathogens were observed.
Visible Light Photoelectrochemical Sensor for Acetaminophen Determination using a Glassy Carbon Electrode Modified with BiVO4 Nanoparticles
Authors: da Silva Araújo Mayara , Barretto Túlio Rolim , Galvão Juliana Costa Rolim , Tarley César Ricardo Teixeira , Dall'Antônia Luiz Henrrique , de Matos Roberto , Medeiros Roberta Antigo
Published: August 2020

A new and simple photoelectrochemical (PEC) sensor using a glassy carbon electrode (GCE) modified with bismuth vanadate (BiVO4) nanoparticles and dihexadecyl phosphate (DHP) film was useful for acetaminophen (AC) determination. In 0.2 mol L−1 phosphate buffer (pH=9), the GCE without modification exhibited the smaller photocurrent (0.86 μA) when compared with GCE modified with 1.0 mg mL−1 or 2.0 mg mL−1 BiVO4 nanoparticles suspension (5.9 and 34 μA, respectively). Based on the photocurrent signal generated through the interaction between GCE, BiVO4 and the energy of visible light a chronoamperometric method for AC determination was developed. The AC linear range concentration from 0.099 to 0.99 μmol L−1 and limits of detection and quantification of 0.027 and 0.091 μmol L−1, respectively, was obtained. The proposed method was applied to the AC determination in commercial drugs and tap water with satisfactory accuracy and precision. Moreover, the PEC construction was easy and had a short response time, which might confer higher sample throughput for the method.
Massively parallel sequencing of STRs using a 29‐plex panel reveals stutter sequence characteristics
Authors: Wu Hao , Ji Ai‐Cen , Liu Yi‐Cheng , Kang Ke‐Lai , Zhang Chi , Li Zhi‐Wen , Ji An‐Quan , Ye Jian , Nie Sheng‐Jie , Wang Le
Published: August 2020

Massively parallel sequencing of forensic STRs simultaneously provides length‐based genotypes and core repeat sequences as well as flanking sequence variations. Here, we report primer sequences and concentrations of a next‐generation sequencing (NGS)‐based in‐house panel covering 28 autosomal STR loci (CSF1PO, D1GATA113, D1S1627, D1S1656, D1S1677, D2S441, D2S1776, D3S3053, D5S818, D6S474, D6S1017, D6S1043, D8S1179, D9S2157, D10S1435, D11S4463, D13S317, D14S1434, D16S539, D18S51, D18S853, D20S482, D20S1082, D22S1045, FGA, TH01, TPOX, and vWA) and the sex determinant locus Amelogenin. Preliminary evaluation experiments showed that the panel yielded intralocus‐ and interlocus‐balanced sequencing data with a sensitivity as low as 62.5 pg input DNA. A total of 203 individuals from Yunnan Bai population were sequenced with this panel. Comparative forensic genetic analyses showed that sequence‐based matching probability of this 29‐plex panel reached 2.37 × 10−29, which was 23 times lower than the length‐based data. Compound stutter sequences of eight STRs were compared with parental alleles. For seven loci, repeat motif insertions or deletions occurred in the longest uninterrupted repeat sequences (LUS). However, LUS and non‐LUS stutters co‐existed in the locus D6S474 with different sequencing depth ratios. These results supplemented our current knowledge of forensic STR stutters, and provided a sound basis for DNA mixture deconvolution.
Bulimia nervosa in times of the COVID‐19 pandemic—Results from an online survey of former inpatients
Authors: Schlegl Sandra , Meule Adrian , Favreau Matthias , Voderholzer Ulrich
Published: August 2020

Objective

The COVID‐19 pandemic might pose special challenges to patients with eating disorders (EDs) by interfering with daily routines. The aim of this study was to investigate the impact of the current pandemic on patients with bulimia nervosa (BN).

Methods

Fifty‐five former inpatients with BN completed an online survey on psychological consequences of the COVID‐19 pandemic as well as on changes in health care utilisation and on the use and helpfulness of different coping strategies.

Results

Almost half of patients (49%) reported a deterioration of their ED symptomatology and 62% reported a reduced quality of life. The frequency of binge eating increased in 47% of patients and self‐induced vomiting in 36%. Forty‐six percent of patients stated a noticeable impairment of psychotherapy. Face‐to‐face psychotherapy decreased by 56% but videoconferencing therapy was only used by 22% of patients. Enjoyable activities, virtual social contacts with friends and mild physical activities were rated as the most helpful coping strategies among those most used.

Discussion

Approximately one half to two‐thirds of former inpatients with BN experienced a negative impact of the crisis on their ED symptomatology and quality of life. In challenging times when face‐to‐face therapy options are restricted, e‐health treatments such as videoconferencing therapy should be considered to ensure continuity of care.
A novel high polymer nanocomposite inhibitor for coal gangue spontaneous combustion prevention: A case study of Yangquan coal gangue in China
Authors: Huang Zhian , Le Tian , Gao Yukun , Shao Zhenlu , Zhang Yinghua , Li Jinyang , Ma Zhenzhen
Published: August 2020

Coal gangue spontaneous combustion produces toxic and harmful gases. This research aims to study a new type of polymer nanocomposite inhibitor to prevent and control coal gangue spontaneous combustion. Nanomodification of montmorillonite (MMT) was carried out on high polymer emulsion inhibitor polyacrylamide (PAM) to improve its thermal stability and overcome the short inhibition duration problem. First, through scanning electron microscope (SEM), energy‐dispersive spectrometer (EDS), and proximate analysis experiments, it was found that the coal gangue in the Yangquan mining area was prone to spontaneous combustion. Then, PAM/MMT was produced by an intercalation method. The results of X‐ray diffraction (XRD) and differential scanning calorimetry (DSC) showed that the interval spacing of MMT increased, which was sufficient for the insertion of acrylamide monomer. The vitrification temperatures of PAM and PAM/MMT prove that PAM/MMT exhibited higher thermal stability. The results of Fourier transform infrared spectroscopy (FTIR) experiments indicated that the PAM/MMT composite inhibitor agent effectively inhibited the oxidative activity of reactive groups on the coal gangue surface. As a result, PAM/MMT could suppress coal gangue oxidative spontaneous combustion, so as to reduce environmental problems caused by coal gangue spontaneous combustion. Furthermore, a spraying process is designed for the application of the inhibitor.
Lactobacillus plantarum KSFY06 and geniposide counteract montmorillonite‐induced constipation in Kunming mice
Authors: Gan Yi , Liang Jie , Diao Wenjing , Zhou Xianrong , Mu Jianfei , Pang Liang , Tan Fang , Zhao Xin
Published: August 2020

Constipation is a common clinical manifestation of digestive system disorders and occurs worldwide. This study investigated the ability of Lactobacillus plantarum KSFY06 (LP‐KSFY06) to promote the action of geniposide in preventing montmorillonite‐induced constipation in Kunming mice, with the aim of providing a successful solution. The effects of LP‐KSFY06 and geniposide on constipation were measured, and the results showed that the protective effect of geniposide on constipation was enhanced by LP‐KSFY06 and that the combination resulted in increased weight, moisture content, and particle number of feces. The first black stool defecation time was decreased from 182 min to 87 min, which clearly indicates that defecating difficulty was alleviated in constipated mice. The synergic intervention of LP‐KSFY06 and geniposide (LP + G) assisted in maintaining the body weight of constipated mice. The LP + G intervention significantly increased serum levels of motilin (MTL, 167.8 pg/ml), acetylcholinesterase (AChE, 45.3 pg/ml), substance P (SP, 61.0 pg/ml), vasoactive intestinal peptide (VIP, 70.5 pg/ml), endothelin‐1 (ET‐1, 16.1 pg/ml), and gastrin (73.0 pg/ml) and remarkably decreased somatostatin (SS, 35.2 pg/ml) when compared to those indexes in the LP‐KSFY06 group and geniposide group. The LP + G treatment also significantly increased the mRNA expression of cluster of differentiation 117 (c‐Kit), stem cell factor (SCF), glial cell‐derived neurotrophic factor (GDNF), and remarkably downregulated the expression of inducible nitric oxide synthase (iNOS), transient receptor potential vanilloid‐1 (TRPV1), and cyclooxygenase‐2 (COX‐2). The experimental results showed that the combination treatment has the strongest prevention effect against constipation, and LP‐KSFY06 promotes the ability of geniposide to prevent constipation. Therefore, LP‐KSFY06 is a potential probiotic strain with the capacity to prevent montmorillonite‐induced constipation.
Successful use of a therapeutic trial of graduated volume and dose escalation for postoperative head and neck radiotherapy in a Fanconi anemia patient
Authors: Lewis Luke M , Tang Alice L , Wise‐Draper Trisha M , Myers Kasiani C , Greenberger Joel S , Takiar Vinita
Published: August 2020

Background

Patients with the heritable disease, Fanconi anemia (FA), have a 500‐fold risk of developing head and neck squamous cell carcinomas (HNSCC). However, the use of conventional cytotoxic agents including radiation therapy and cisplatin‐based chemotherapy is contraindicated in patients with FA due to underlying DNA repair defects.

Methods/Results

We present a young FA patient with recurrent HNSCC and high‐risk pathologic features treated with a therapeutic trial of chemoradiation. This novel strategy employs a gentle radiation dose and volume escalation with concurrent pembrolizumab. The patient completed the entire course of therapy with no treatment delays or interruptions.

Conclusions

The FA patient population has a clear need for adjuvant treatment regimens given their predilection for HNSCC. A therapeutic trial may allow FA and other radiosensitive patients to trial radiation with the option to terminate treatment before any severe side effects occur and for some to complete a full course of treatment.