bluuebunny/crossref_metadata_2025 huggingface dataset:
Positron Emission Tomography–Driven Strategy in Advanced Hodgkin Lymphoma: Prolonged Follow-Up of the AHL2011 Phase III Lymphoma Study Association Study
Authors: Casasnovas René-Olivier , Bouabdallah Reda , Brice Pauline , Lazarovici Julien , Ghesquieres Hervé , Stamatoullas Aspasia , Dupuis Jehan , Gac Anne-Claire , Gastinne Thomas , Joly Bertrand , Bouabdallah Krimo , Nicolas-Virelizier Emmanuelle , Feugier Pierre , Morschhauser Franck , Sibon David , Bonnet Christophe , Berriolo-Riedinger Alina , Edeline Véronique , Parrens Marie , Damotte Diane , Coso Diane , André Marc , Meignan Michel , Rossi Cédric
Published: January 2022

PURPOSE

The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747 ) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results.

METHODS

Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2– and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment.

RESULTS

In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2–/PET4–, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4– and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4– patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2–/PET4– patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively.

CONCLUSION

The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis.
Pembrolizumab in Patients With Microsatellite Instability–High Advanced Endometrial Cancer: Results From the KEYNOTE-158 Study
Authors: O'Malley David M. , Bariani Giovanni Mendonca , Cassier Philippe A. , Marabelle Aurelien , Hansen Aaron R. , De Jesus Acosta Ana , Miller Wilson H. , Safra Tamar , Italiano Antoine , Mileshkin Linda , Xu Lei , Jin Fan , Norwood Kevin , Maio Michele
Published: January 2022

PURPOSE

Pembrolizumab demonstrated durable antitumor activity in patients with previously treated, advanced microsatellite instability–high or mismatch repair–deficient (MSI-H/dMMR) tumors, including endometrial cancer, in the nonrandomized, open-label, multicohort, phase II KEYNOTE-158 study ( NCT02628067 ). We report efficacy and safety outcomes for patients with MSI-H/dMMR endometrial cancer enrolled in KEYNOTE-158.

METHODS

Eligible patients from cohorts D (endometrial cancer, regardless of MSI-H/dMMR status) and K (any MSI-H/dMMR solid tumor, except colorectal) with previously treated, advanced MSI-H/dMMR endometrial cancer received pembrolizumab 200 mg once every 3 weeks for 35 cycles. The primary end point was objective response rate per RECIST version 1.1 by independent central radiologic review. Secondary end points included duration of response, progression-free survival, overall survival, and safety.

RESULTS

As of October 5, 2020, 18 of 90 treated patients (20%) had completed 35 cycles of pembrolizumab and 52 (58%) had discontinued treatment. In the efficacy population (patients who received ≥ 1 dose of pembrolizumab and had ≥ 26 weeks of follow-up; N = 79), the median time from first dose to data cutoff was 42.6 (range, 6.4-56.1) months. The objective response rate was 48% (95% CI, 37 to 60), and median duration of response was not reached (2.9-49.7+ months). Median progression-free survival was 13.1 (95% CI, 4.3 to 34.4) months, and median overall survival was not reached (95% CI, 27.2 months to not reached). Among all treated patients, 76% had ≥ 1 treatment-related adverse event (grades 3-4, 12%). There were no fatal treatment-related events. Immune-mediated adverse events or infusion reactions occurred in 28% of patients (grades 3-4, 7%; no fatal events).

CONCLUSION

Pembrolizumab demonstrated robust and durable antitumor activity and encouraging survival outcomes with manageable toxicity in patients with previously treated, advanced MSI-H/dMMR endometrial cancer.
Opioid Prescription Is Associated With Increased Survival in Older Adult Patients With Pancreatic Cancer in the United States: A Propensity Score Analysis
Authors: Zylberberg Haley M. , Woodrell Christopher , Rustgi Sheila D. , Aronson Anne , Kessel Elizabeth , Amin Sunil , Lucas Aimee L.
Published: January 2022

PURPOSE:

Few studies have assessed the interaction between pain treatment and mortality in pancreatic cancer. The aim of this study was to investigate the association between receipt of opioid prescriptions and survival in adults with pancreatic cancer.

METHODS:

The SEER-Medicare linked database was used to identify patients diagnosed with late-stage pancreatic cancer between 2007 and 2015. Kaplan-Meier models were used to assess the association between opioid prescriptions in the year after cancer diagnosis and survival. Cox proportional hazard models were used to determine the association between opioid receipt and survival, adjusting for propensity score and other relevant confounders including cancer-directed therapies and palliative care referral.

RESULTS:

A total of 5,770 older adults with pancreatic cancer were identified; 1,678 (29.1%) were prescribed opioids for at least 60 days. Median survival was increased in those with opioid prescriptions (6.0 months) compared with those without (4.0 months, P < .0001). After adjustment for confounders, opioid prescriptions were still associated with improved survival (hazard ratio 0.80; 95% CI, 0.75 to 0.86). On multivariable analysis, opioid prescriptions were associated with older age, female sex, residing in nonmetro areas, and treatment with celiac plexus neurolysis, chemotherapy, and radiation.

CONCLUSION:

Receipt of opioid prescriptions is associated with longer survival in patients with pancreatic cancer. This may be due to the impact of cancer-related pain, although further studies are needed to better understand the interaction between pain management, cancer-directed therapies, and systemic factors, such as palliative care, availability of opioids, and clinical practice culture.
Impact of COVID-19 on Hematology-Oncology Trainees: A Quantitative and Qualitative Assessment
Authors: Durani Urshila , Major Ajay , Velazquez Ana I. , May Jori , Nelson Marquita , Zheng Ze , Hall Anurekha G. , Alam Sara Taveras , Reynolds Robby , Thompson J. Colton , Kumbamu Ashok , Das Devika G. , Murphy Martina C. , Henry Elizabeth , Lee Alfred Ian , Marshall Ariela L. , Wun Ted , Weeks Lachelle Dawn
Published: January 2022

PURPOSE:

Graduate medical and research training has drastically changed during the COVID-19 pandemic, with widespread implementation of virtual learning, redeployment from core rotations to the care of patients with COVID-19, and significant emotional and physical stressors. The specific experience of hematology-oncology (HO) fellows during the COVID-19 pandemic is not known.

METHODS:

We conducted a mixed-methods study using a survey of Likert-style and open-ended questions to assess the training experience and well-being of HO fellows, including both clinical and postdoctoral trainee members of the American Society of Hematology and ASCO.

RESULTS:

A total of 2,306 surveys were distributed by e-mail; 548 (23.8%) fellows completed the survey. Nearly 40% of fellows felt that they had not received adequate mental health support during the pandemic, and 22% reported new symptoms of burnout. Pre-existing burnout before the pandemic, COVID-19–related clinical work, and working in a primary research or nonclinical setting were associated with increased burnout on multivariable logistic regression. Qualitative thematic analysis of open-ended responses revealed significant concerns about employment after training completion, perceived variable quality of virtual education and board preparation, loss of clinical opportunities to prepare for independent clinical practice, inadequate grant funding opportunities in part because of shifting research priorities, variable productivity, and mental health or stress during the pandemic.

CONCLUSION:

HO fellows have been profoundly affected by the pandemic, and our data illustrate multiple avenues for fellowship programs and national organizations to support both clinical and postdoctoral trainees.
Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer
Authors: Asghar Uzma S. , Kanani Ruhi , Roylance Rebecca , Mittnacht Sibylle
Published: January 2022

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have revolutionized the treatment of hormone-positive metastatic breast cancers (mBCs). They are currently established as standard therapies in combination with endocrine therapy as first- and second-line systemic treatment options for both endocrine-sensitive and endocrine-resistant mBC populations. In the first-line metastatic setting, the median progression-free survival for the three currently approved CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, with aromatase inhibitors is greater than 2 years (palbociclib 27.6 months; ribociclib 25.3 months; and abemaciclib 28.18 months). Although CDK4/6 inhibitors have significant clinical benefits and enable physicians to delay starting chemotherapy, they are expensive and can be associated with drug toxicities. Here, we have performed a systemic review of the reported molecular markers predictive of drug response including intrinsic and acquired resistance for CDK4/6 inhibition in mBC. The rapidly emerging molecular landscape is captured through next-generation sequencing of breast cancers (DNA with or without RNA), liquid biopsies (circulating tumor DNA), and protein analyses. Individual molecular candidates with robust and reliable evidence are discussed in more depth.
A Full Evaporation Static Headspace Gas Chromatography Method with Nitrogen Phosphorous Detection for Ultrasensitive Analysis of Semi-volatile Nitrosamines in Pharmaceutical Products
Authors: Zheng Jinjian , Kirkpatrick Christine L. , Lee Daniel , Han Xinxin , Martinez Ana I. , Gallagher Kimberly , Evans Rebecca K. , Mudur Sanjay V. , Liang Xihui , Drake Jennifer , Buhler Leah A. , Mowery Mark D.
Published: January 2022

The recent detection of potent carcinogenic nitrosamine impurities in several human medicines has triggered product recalls and interrupted the supply of critical medications for hundreds of millions of patients, illuminating the need for increased testing of nitrosamines in pharmaceutical products. However, the development of analytical methods for nitrosamine detection is challenging due to high sensitivity requirements, complex matrices, and the large number and variety of samples requiring testing. Herein, we report an analytical method for the analysis of a common nitrosamine, N-nitrosodimethylamine (NDMA), in pharmaceutical products using full evaporation static headspace gas chromatography with nitrogen phosphorous detection (FE-SHSGC-NPD). This method is sensitive, specific, accurate, and precise and has the potential to serve as a universal method for testing all semi-volatile nitrosamines across different drug products. Through elimination of the detrimental headspace-liquid partition, a quantitation limit of 0.25 ppb is achieved for NDMA, a significant improvement upon traditional LC-MS methods. The extraction of nitrosamines directly from solid sample not only simplifies the sample preparation procedure but also enables the method to be used for different products as is or with minor modifications, as demonstrated by the analysis of NDMA in 10+ pharmaceutical products. The in situ nitrosation that is commonly observed in GC methods for nitrosamine analysis was completely inhibited by the addition of a small volume solvent containing pyrogallol, phosphoric acid, and isopropanol. Employing simple procedures and low-cost instrumentation, this method can be implemented in any analytical laboratory for routine nitrosamine analysis, ensuring patient safety and uninterrupted supply of critical medications.
Stochastic dynamics of chemotactic colonies with logistic growth
Authors: Ben Alì Zinati Riccardo , Duclut Charlie , Mahdisoltani Saeed , Gambassi Andrea , Golestanian Ramin
Published: January 2022

The interplay between cellular growth and cell-cell signaling is essential for the aggregation and proliferation of bacterial colonies, as well as for the self-organization of cell tissues. To investigate this interplay, we focus here on the collective properties of dividing chemotactic cell colonies by studying their long-time and large-scale dynamics through a renormalization group (RG) approach. The RG analysis reveals that a relevant but unconventional chemotactic interaction —corresponding to a polarity-induced mechanism— is generated by fluctuations at macroscopic scales, even when an underlying mechanism is absent at the microscopic level. This emerges from the interplay of the well-known Keller-Segel (KS) chemotactic nonlinearity and cell birth and death processes. At one-loop order, we find no stable fixed point of the RG flow equations. We discuss a connection between the dynamics investigated here and the celebrated Kardar-Parisi-Zhang (KPZ) equation with long-range correlated noise, which points at the existence of a strong-coupling, nonperturbative fixed point.
Intralesional Bleomycin Injection and Skin Hyperpigmentation: A Case Series of a Single-Center Experience With a Standardized Skin-Protective Protocol
Authors: Heninger Jacob , Cheon Eric , Green Jared , Hajduk John , Benzon Hubert
Published: January 2022

Bleomycin is a cytotoxic antibiotic that has a sclerosing effect on vascular endothelium. Small doses can be injected locally to reduce the size of various vascular malformations. Recognition that targeted intralesional injection carries the potential to cause hyperpigmentation, specifically in areas of skin trauma, and has led our department to implement a bleomycin skin-protective protocol. On review of cases performed following protocol implementation, no patients developed hyperpigmentation attributable to iatrogenic skin trauma. We present our bleomycin skin protection protocol to guide peer institutions in the initiation of similar quality improvement initiatives.
Rainforest Capitalism
Authors: Hendriks Thomas
Published: January 2022

Congolese logging camps are places where mud, rain, fuel smugglers, and village roadblocks slow down multinational timber firms; where workers wage wars against trees while evading company surveillance deep in the forest; where labor compounds trigger disturbing colonial memories; and where blunt racism, logger machismo, and homoerotic desires reproduce violence. In Rainforest Capitalism Thomas Hendriks examines the rowdy world of industrial timber production in the Democratic Republic of the Congo to theorize racialized and gendered power dynamics in capitalist extraction. Drawing on ethnographic fieldwork among Congolese workers and European company managers as well as traders, farmers, smugglers, and barkeepers, Hendriks shows how logging is deeply tied to feelings of existential vulnerability in the face of larger forces, structures, and histories. These feelings, Hendriks contends, reveal a precarious side of power in an environment where companies, workers, and local residents frequently find themselves out of control. An ethnography of complicity, ecstasis, and paranoia, Rainforest Capitalism queers assumptions of corporate strength and opens up new ways to understand the complexities and contradictions of capitalist extraction.
Irreversible impact of early thermal conditions: an integrative study of developmental plasticity linked to mobility in a butterfly species
Authors: Degut Anaïs , Fischer Klaus , Quque Martin , Criscuolo François , Michalik Peter , Beaulieu Michaël
Published: January 2022

Within populations, phenotypic plasticity may allow adaptive phenotypic variation in response to selection generated by environmental heterogeneity. For instance, in multivoltine species, seasonal changes between and within generations may trigger morphological and physiological variation enhancing fitness under different environmental conditions. These seasonal changes may irreversibly affect adult phenotypes when experienced during development. Yet, the irreversible effects of developmental plasticity on adult morphology have rarely been linked to life-history traits even though they may affect different fitness components such as reproduction, mobility and self-maintenance. To address this issue, we raised larvae of Pieris napi butterflies under warm or cool conditions to subsequently compare adult performance in terms of reproduction performance (as assessed through fecundity), displacement capacity (as assessed through flight propensity and endurance) and self-maintenance (as assessed through the measurement of oxidative markers). As expected in ectotherms, individuals developed faster under warm conditions and were smaller than individuals developing under cool conditions. They also had more slender wings and showed a higher wing surface ratio. These morphological differences were associated with changes in the reproductive and flight performance of adults, as individuals developing under warm conditions laid fewer eggs and flew larger distances. Accordingly, the examination of their oxidative status suggested that individuals developing under warm conditions invested more strongly into self-maintenance than individuals developing under cool conditions (possibly at the expense of reproduction). Overall, our results indicate that developmental conditions have long-term consequences on several adult traits in butterflies. This plasticity probably acts on life-history strategies for each generation to keep pace with seasonal variations and may facilitate acclimation processes in the context of climate change.
A change in taste: the role of microRNAs in altering hedonic value
Authors: Kagan Diana , Batabyal Anuradha , Rivi Veronica , Lukowiak Ken
Published: January 2022

The mechanisms associated with neophobia and anhedonia remain largely unknown. Neuropsychological disorders such as depression and schizophrenia are associated with excessive fear and anhedonia, and have been linked to microRNA 137. We hypothesized that microRNAs (miRNAs) in the snail Lymnaea stagnalis are important for regulating feeding behaviour through either preventing neophobia or establishing hedonic value. To test these hypotheses, we used an injection of poly-l-lysine (PLL) to inhibit miRNA biogenesis and observed its effects on feeding behaviour. We repeated these experiments with pre-exposure to novel stimuli capable of eliciting neophobia to disentangle the processes predicted to regulate feeding behaviour. Next, we exposed snails to food stimuli of high hedonic value after PLL injection to reset their hedonic value for that food. Finally, we consolidated our results with previous research by examining the effect of PLL injection on a one-trial appetitive classical conditioning procedure (1TT) to induce long-term memory (LTM). We found that miRNAs are likely not required for preventing neophobia. Moreover, we discovered that snails experienced anhedonia in response to inhibition of miRNA biogenesis, resulting in diminished feeding behaviour for food stimuli with a previously high hedonic value. Snails showed diminished feeding behaviour for multiple food stimuli of high hedonic value post-1TT with PLL injection. This finding suggests that PLL causes anhedonia rather than an impairment of LTM formation following the 1TT procedure. This is the first evidence suggesting that inhibiting the biogenesis of miRNAs contributes to anhedonia in L. stagnalis.
Dynamic contrast-enhanced breast magnetic resonance imaging findings that affect the magnetic resonance-directed ultrasound correlation of non-mass enhancement lesions: a single-center retrospective study
Authors: Coskun Bilge Almila , Demir Pinar Ilhan , Aydin Hale , Bostanci Isil Esen
Published: January 2022

Objective:

Our single-center retrospective study aimed to evaluate the relationship between magnetic resonance (MR)-directed ultrasound (MDUS) detectability and MRI findings of non-mass enhancement (NME) lesions, regarding the morphologic and enhancement features, the distance from the skin and nipple, and the presence of concomitant landmarks.

Methods:

A total of 350 MRI-detected NME lesions that were determined between January 2015 and May 2019 and subsequently underwent MDUS were analyzed. The MRI findings, biopsy results, and follow-up outcomes of lesions were recorded. The correlation between the MRI findings of the lesions and MDUS detectability was analyzed.

Results:

114 (32.6%) of the 350 lesions had a counterpart in the MDUS. Respectively, 66 (37.9%), 38 (43.2%) and 59 (38.3%) of the lesions detected in MDUS were larger than 20 mm in size, with a distance of less than 20 mm to the nipple and 15 mm to the skin. The lesion size and lesion distance to the nipple and skin were significantly associated with a ultrasound correlate (p < 0.05). The MDUS detection rate was significantly higher in NME lesions with MR findings including diffuse distribution (p < 0.001), clustered-ring enhancement pattern (p < 0.001), washout kinetic curve (p = 0.006), and MR-BIRADS category 5 (p < 0.001). Multivariate logistic regression showed that only the clustered-ring enhancement pattern was significantly associated with an MDUS correlation (p < 0.001).

Conclusion:

Statistically significant correlations were found between the size, distance to the nipple and skin, distribution pattern, enhancement pattern and kinetic curve of the NME lesions on MRI and ultrasound detectability.

Advances in knowledge:

We found that clustered-ring enhancement patterns were significantly more frequent in MR-directed ultrasound detectable lesions.
A vaginal fibroepithelial stromal polyp: a case report with magnetic resonance images
Authors: Ogura Naoko , Inagaki Mieko , Yasuda Ritsuko , Yoshida Shigeki , Maeda Tetsuo
Published: January 2022

A fibroepithelial stromal polyp is a benign soft tissue tumour that can occur in the vagina, vulva and uterine cervix. Magnetic resonance imaging (MRI) findings have been reported in patients with vulvar fibroepithelial stromal polyps, not in those with vaginal polyps. We present MRI findings of vaginal fibroepithelial stromal polyp in a postmenopausal female. A 1 to 2 cm firm vaginal mass arising from the left side of the vaginal wall with hypointense signal changes on T1W MRI was identified. A well-defined vaginal mass (1 cm diameter) was detected with inhomogeneous signal intensity on T2W images. However, a major portion had high signal intensity on diffusion-weighted images. A benign vaginal lesion with oedematous changes or myxoid degeneration was suspected. Vaginal resection was performed, and fibroepithelial stromal polyp was pathologically diagnosed. MRI may be a useful non-invasive modality for preoperatively diagnosing vaginal fibroepithelial stromal polyps.
Assessment of risk perception and risk communication regarding COVID-19 among healthcare providers: An explanatory sequential mixed-method study in Bangladesh
Authors: Salwa Marium , Atiqul Haque M , Ibrahim Ibne Towhid Muhmammad , Sultana Sarmin , Tanvir Islam Mohammad , Maruf Haque Khan Md , Miah Md Titu , Islam Syed Shariful , Moniruzzaman Syed
Published: January 2022

Background: Any public health emergency demands adequate risk communication with the vulnerable population along with their optimized perception about the impending risk to ensure proper risk management and crisis control. Hence, we conducted this study to explore healthcare providers’ perceptions regarding risks of coronavirus disease 2019 (COVID-19), as well as how they are being communicated to about the risk, and how they practice risk reduction measures.

Methods: We conducted a two-phased explanatory sequential mixed-method study among physicians and nurses from randomly selected tertiary healthcare facilities in Dhaka, the capital of Bangladesh. In the first phase, we assessed the general pattern and quantifiable measures of risk perception, risk communication, and infection prevention practices quantitatively. We performed multiple linear regression analyses to explore how much variability of risk perception was predicted by risk communication methods and contents. In the second phase, we collected qualitative data for in-depth understanding and exploration of participants’ experiences and insights regarding COVID-19 risk through interviews and document reviews. We manually performed thematic content analysis of the qualitative data. Finally, we triangulated findings from both phases to illustrate the research objectives.

Discussion: Based on the psychometric dimensions of risk perception and psycho-social theory of the health belief model, perceptions of COVID-19 risk among healthcare providers were evaluated in this study. The relationship between risk perception and infection prevention and control practices among healthcare providers were also investigated. The explanatory sequential design of this study is expected to generate hypotheses on how risk perception is being shaped in a time of uncertainty and, thus, will help to build a proper risk communication strategy for the healthcare providers
Prediction of the Effects of Nonsynonymous Variants on SARS-CoV-2 Proteins
Authors: Sia Boon Zhan , Boon Wan Xin , Yap Yoke Yee , Kumar Shalini , Ng Chong Han
Published: January 2022

Background: SARS-CoV-2 virus is a highly transmissible pathogen that causes COVID-19. The outbreak originated in Wuhan, China in December 2019. A number of nonsynonymous mutations located at different SARS-CoV-2 proteins have been reported by multiple studies. However, there are limited computational studies on the biological impacts of these mutations on the structure and function of the proteins.  

Methods: In our study nonsynonymous mutations of the SARS-CoV-2 genome and their frequencies were identified from 30,229 sequences. Subsequently, the effects of the top 10 nonsynonymous mutations of different SARS-CoV-2 proteins were analyzed using bioinformatics tools including co-mutation analysis, prediction of the protein structure stability and flexibility analysis, and prediction of the protein functions.  

Results: A total of 231 nonsynonymous mutations were identified from 30,229 SARS-CoV-2 genome sequences. The top 10 nonsynonymous mutations affecting nine amino acid residues were ORF1a nsp5 P108S, ORF1b nsp12 P323L and A423V, S protein N501Y and D614G, ORF3a Q57H, N protein P151L, R203K and G204R. Many nonsynonymous mutations showed a high concurrence ratio, suggesting these mutations may evolve together and interact functionally. Our result showed that ORF1a nsp5 P108S, ORF3a Q57H and N protein P151L mutations may be deleterious to the function of SARS-CoV-2 proteins. In addition, ORF1a nsp5 P108S and S protein D614G may destabilize the protein structures while S protein D614G may have a more open conformation compared to the wild type.  

Conclusion: The biological consequences of these nonsynonymous mutations of SARS-CoV-2 proteins should be further validated by in vivo and in vitro experimental studies in the future.
The algorithm of the electric stimulator VEB-1 software operation
Authors: Babelyuk V. , Dobrovolsky Yu. , Korsuns’kyi I. , Kuzenko V. , Popovych I. , Zukow W.
Published: January 2022

This thesis demonstrates results of the electric stimulator VEB-1 software operation algorithm development. To increase the device efficiency, the algorithm is composed using the frequency beat method. Our software solutions allowed us to provide the needed precision to maintain the operating frequency of the electric current pulses that penetrate through the human body on the level not less than 0,001Hz. The software allows the operator to control the electrostimulation process through the screen, where all active processes are displayed.
Influence of platelet-enriched plasma on the morpho-functional state of liver in rats with induced non-alcoholic steatohepatitis and dyslipidemia
Authors: Appelhans O. , Maznichenko I. , Kasatkin O. , Hussein Abdulla , Biriuk M. , Romak O.
Published: January 2022

Non-alcoholic steatohepatitis (NASH) is a consequence of the progression of non-alcoholic fatty liver disease (NAFLD), which can lead to cirrhosis or hepatocellular insufficiency. NAFLD is a predictor of cardiovascular diseases (CVD) development. The important factor of the latter development is atherogenic dyslipidemia, and this is a type of 20-80 % NASH patients. The objective: to study the effectiveness of platelet-enriched plasma (PRP) influence on the morpho-functional state of liver in rats with non-alcoholic steatohepatitis. Materials and methods. The study was carried out on 80 adult male Wistar rats. Animals were divided into three groups: I group - animals that received an atherogenic diet for 90 days (n=10);  II group - animals with simulated NASH and DL which received a normal diet for 30 days (n=30); III group - animals with simulated NASH and DL and PRP correction (n=30); group of intact animals (n=10). NASH was simulated by introducing an atherogenic diet, which consisted of lard and 50 g / kg of butter for 90 days. PRP was punctured in the tissue of liver, twice at 0.05 ml with 7 days interval. The animals were taken out of the experiment after 90 days of the atherogenic diet  and on the 30th day after its cessation or PRP injection. The indicators of body mass, liver mass index (LMI), lipogram, hepatic transaminases were determined, and the further pathological examination of the liver tissue was done. Results and discussion. On the 90th day of the atherogenic diet, the GH level was 3.19 ± 0.56 mmol/l, ALT activity was 118 ± 6.12 U/l, AST 86 ± 4.52 U/l, morphological signs of NASH were detected. On the 30th day, the lipid profile of group II rats did not have statistical differences from group I, in rats after correction of NASH with the use of  PRP the level of LLD decreased by 51%, ALT activity - by 54%, AST - by 51% compared to control group (p <0.05), morphologically revealed I - II degree steatosis, focal protein dystrophy. Conclusions. On the 90th day of an atherogenic diet NASH was formed in experimental animals. They had dyslipidemia, which progressed for at least 30 days while maintaining a usual diet. After correction with PRP the level of atherogenic lipoproteins was significantly decreased in rats with NASH and DL; the activity of liver enzymes was lower compared to the group with simulated NASH and DL and the group with progression of NASH and DL for 30 days, morphologically the decrease in liver steatosis and severity of protein dystrophy comparing with a group with simulated NASH and DL and a group with progressive NASH and DL was observed for 30 days.
Do You Really Know if It’s True? How Asking Users to Rate Stories Affects Belief in Fake News on Social Media
Authors: Moravec Patricia L. , Kim Antino , Dennis Alan R. , Minas Randall K.
Published: January 2022

Research shows that consuming ratings influences purchase decisions in e-commerce and also has modest effects on belief in news articles on social media. We find that the act of producing ratings reduces belief in news articles on social media and induces social media users to think more critically. We propose this intervention as a method to encourage users to realize that, unlike in the product rating setting, social media users who submit their ratings for news articles typically lack firsthand knowledge of the events reported in the news, making it difficult for most users to rate news articles accurately. We asked 68 social media users to assess the believability of 42 social media articles and measured their cognitive activity using electroencephalography. We found that asking users to rate articles using a self-referential question induced them to think more critically—as indicated by increased activation in the medial prefrontal cortex and dorsolateral prefrontal cortex—and made them less likely to believe the articles. The effect extended to subsequent articles; after being asked to rate an article, users were less likely to believe other articles that followed it whether they were asked to rate them or not.
Curbing the Opioid Epidemic at Its Root: The Effect of Provider Discordance After Opioid Initiation
Authors: Bobroske Katherine , Freeman Michael , Huan Lawrence , Cattrell Anita , Scholtes Stefan
Published: January 2022

Although medical research has addressed the clinical management of chronic opioid users, little is known about how operational interventions shortly after opioid initiation can impact a patient’s likelihood of long-term opioid use. Using a nationwide U.S. database of medical and pharmaceutical claims, we investigate the care delivery process at the most common entry point to opioid use: the primary care setting. For patients who return to primary care for a follow-up appointment within 30 days of opioid initiation, we ask who should revisit and potentially revise the opioid-based treatment plan: the initial prescriber (provider concordance) or an alternate clinician (provider discordance)? First, using a fully controlled logistic model, we find that provider discordance reduces the likelihood of long-term opioid use 12 months after opioid initiation by 31% (95% Confidence Interval: [18%, 43%]). Both the instrumental variable analysis technique and propensity-score matching (utilizing the minimum-bias estimator approach) account for omitted variable bias and indicate that this is a conservative estimate of the true causal effect. Second, looking at patient activities immediately after the follow-up appointment, we find that this long-term reduction is at least partially explained by an immediate reduction in opioids prescribed after the follow-up appointment. Third, the data suggest that the benefit associated with provider discordance remains significant regardless of whether the patient’s initial prescriber was their regular primary care provider or another clinician. Overall, our analysis indicates that systematic, operational changes in the early stages of managing new opioid patients may offer a promising, and hitherto overlooked, opportunity to curb the opioid epidemic.

This paper was accepted by David Simchi-Levi, healthcare management.
Objective Selection for Cancer Treatment: An Inverse Optimization Approach
Authors: Ajayi Temitayo , Lee Taewoo , Schaefer Andrew J.
Published: January 2022

The quality of radiation therapy treatment plans and the efficiency of the planning process are heavily affected by the choice of planning objectives. Although simple objectives enable efficient treatment planning, the resulting treatment quality might not be clinically acceptable; complex objectives can generate high-quality treatment, yet the planning process becomes computationally prohibitive. In “Objective Selection for Cancer Treatment: An Inverse Optimization Approach,” by integrating inverse optimization and feature selection techniques, Ajayi, Lee, and Schaefer propose a novel objective selection method that uses historical radiation therapy treatment data to infer a set of planning objectives that are tractable and parsimonious yet clinically effective. Although the objective selection problem is a large-scale bilevel mixed-integer program, the authors propose various solution approaches inspired by feature selection greedy algorithms and patient-specific anatomical characteristics.
Heterotopic Ossification after Open Anchor Fixation of the Posterior Cruciate Ligament Avulsion in a Multiligament Injury of the Knee: A Case Report
Authors: Mody Aashay , Theja Ramanchandra , Agarwal Saksham , Acharya Kiran , Pandey Vivek
Published: January 2022

Introduction: Heterotopic ossifications (HO) are a well-recognized but infrequently encountered condition. In the lower limb, the literature commonly reports the formation of HO around the hip after surgeries. However, HO is uncommon around the knee and a rare complication after open fixation of posterior cruciate ligament (PCL) avulsion fracture.

Case Report:Here, we describe a case of HO in a 42-year-old patient with multiligament injury, including PCL and arcuate ligament avulsion, partial ACL tear, and medial meniscus root tear with suspected vascular compromise. He underwent open reduction and internal fixation of PCL avulsion fracture and medial meniscus root repair after the injury. At a 6-week follow-up, a plain radiograph revealed posterior capsule HO which kept increasing over successive follow-ups compromising his knee function. The patient was not willing for any mode of intervention for the same at any given time.

Conclusion:HO after open PCL avulsion fixation is an uncommon entity. This article sheds light on how open fixation of PCL bony avulsion in a multiligament injured knee could result in a HO.

Keywords: Posterior cruciate ligament avulsion, multiligament injury, open fixation, suture anchor, heterotopic ossification, posterior capsule.
Image denoising and enhancement strategy based on polarization
detection of space targets
Authors: Miao Shuzhuo , Fan Cunbo , Wen Guanyu , Dong Xue
Published: January 2022

Polarization detection of space targets is one of the most important research
directions in the field of space target recognition. In view of the
fact that there are problems such as strong background noise and
inconspicuous details of contour features in the polarization image of
space targets, an image denoising and enhancement strategy is
proposed. To solve the problem of high intensity of Gaussian noise in
degree of polarization (DoP) images, a denoising method named adaptive
noise template prediction (ANTP) is proposed to eliminate the noise.
Compared to the existing methods, the ANTP algorithm performs better
at reducing noise and improving image quality. Aiming at the
difficulty of separating the background noise from angle of
polarization (AoP) images, a denoising method named gray analysis of
local area (GALA) is proposed. Compared to traditional methods, the
GALA algorithm can effectively extract the contour features of targets
and improve the contrast of AoP images. An image fusion method based
on discrete cosine transform and local spatial frequency (LSF) is used
to fuse the denoised DoP image and AoP image. The experimental results
of the simulated and real space target polarization detection confirm
the effectiveness of our proposed strategy.
PM-PCF birefringence distribution measurement over a wide wavelength
range based on SSFS and LSSI
Authors: Zhang Yongning , Wu Zhiyang , Zhao Wanli , Wang Biyi , Liu Tongyu
Published: January 2022

A linear self-reference spectral interferometry has been proposed to
measure the distribution of polarization-maintaining photonic crystal
fiber (PM-PCF) birefringence over a wide wavelength range combined
with the soliton self-frequency shift and birefringence effect. The
birefringence of PM-PCF is measured experimentally over the range of
800–970 nm, which is larger than

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and shows a segmented change trend.
The air micropore structure has a significant effect on the
characteristics of PM-PCF, which makes it have a highly nonlinear
coefficient, and at the same time, changes the dispersion and
birefringence distributions of the PM-PCF. The distribution of PM-PCF
birefringence, measured by experiment, provides a new dimension for
the design of PM-PCF, which is helpful for a detailed fiber model and
an iterative optimization of fiber structure.
Giant and controllable Goos–Hänchen shift of monolayer graphene strips enabled by a multilayer dielectric grating structure
Authors: Zhang Changwei , Hong Ye , Li Zhengyang , Da Haixia
Published: January 2022

The discovery of monolayer graphene allows the unprecedented chance for exploring its Goos–Hänchen (GH) shift. However, most of the pronounced GH shifts are achieved in various structures with two-dimensional continuous monolayer graphene. Here, we report on the giant GH shift of reflected wave in monolayer graphene strips by constructing the multilayer dielectric grating structure under them. The observed GH shift here is as high as 7000 times that of the incident wave at the near-infrared frequency region, whose magnification is significantly larger than that of the monolayer graphene ribbon array. We further elucidate that the enhanced GH shift originates from the guided mode resonance of the dielectric grating structure and its magnitude and sign can be manipulated by chemical potential of the monolayer graphene strip. Our work enables a promising route for enhancing and controlling the GH shifts of reflected wave in monolayer graphene strips, which might contribute to their applications in biosensors and detectors.
All-optical Ti3C2Tx modulator based on
a sandwich structure
Authors: Li Erkang , Jiang Man , Li Duidui , Wang Ruiduo , Kang Xin , Wang Tianqi , Yan Xiaoxin , Liu Beibei , Ren Zhaoyu
Published: January 2022

All-optical modulators based on

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have recently garnered much attention
due to their broadband light–matter interactions and its ultrafast
carrier dynamics. To investigate the modulation characteristics of
pump intensity and pump light modulation frequency, we establish an
all-optical modulator with a sandwich structure based on

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(polyvinyl alcohol) film. The result
shows that this modulator can achieve a high modulation depth of
12.55 dB and a modulation frequency of 50 kHz corresponding to a
response time at the microsecond scale. The successful preparation of
the modulator is attributed to the saturable absorption
characteristics of the

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. This modulator has great potential
in all-optical communications and ultrafast optical signal
processing.
Statistical features of an electromagnetic Gaussian–Schell model beam propagating through a smoke aerosol environment
Authors: Singh Hemant Kumar , Joshi Deepa , Kanseri Bhaskar
Published: January 2022

In this paper, we investigate both theoretically and experimentally the statistical properties of an electromagnetic Gaussian–Schell model (EMGSM) beam propagating through polluted atmosphere specifically containing smoke aerosol medium. Experimentally, a glass chamber of 1 m length is constructed to mimic the smoky atmosphere inside the laboratory, in which incense sticks are used for smoke aerosol production inside the chamber in a time-controlled manner. An input EMGSM beam having a variable degree of coherence and degree of polarization (DOP) propagates through the aerosol medium, and its coherence and polarization features after propagation are probed. The results show that the coherence features of the vectorial beam are modified significantly by the smoke aerosol medium, while, for the given propagation length of 1 m, the polarization features remain unaffected. We also investigate the coherence features of the EMGSM beam through smoke aerosols in a particular condition when the DOP of the beam is kept zero. These results are expected to provide insights into atmospheric effects on free-space optical communication in real situations when the medium contains air pollution.
Color computational ghost imaging by deep learning based on simulation data training
Authors: Yu Zhan , Liu Yang , Li Jinxi , Bai Xing , Yang Zhongzhuo , Ni Yang , Zhou Xin
Published: January 2022

We present a new color computational ghost imaging strategy using a sole single-pixel detector and training by simulated dataset, which can eliminate the actual workload of acquiring experimental training datasets and reduce the sampling times for imaging experiments. First, the relative responsibility of the color computational ghost imaging device to different color channels is experimentally detected, and then enough data sets are simulated for training the neural network based on the response value. Because the simulation process is much simpler than the actual experiment, and the training set can be almost unlimited, the trained network model has good generalization. In the experiment with a sampling rate of only 4.1%, the trained neural network model can still recover the image information from the blurry ghost image, correct the color distortion of the image, and get a better reconstruction result. In addition, with the increase in the sampling rate, the details and color characteristics of the reconstruction result become better and better. Feasibility and stability of the proposed method have been verified by the reconstruction results of the trained network model on the color objects of different complexities.
Content aware multi-focus image fusion for high-magnification blood film microscopy
Authors: Manescu Petru , Shaw Michael , Zajiczek Lydia Neary- , Bendkowski Christopher , Claveau Remy , Elmi Muna , Brown Biobele J. , Fernandez-Reyes Delmiro
Published: January 2022

Automated digital high-magnification optical microscopy is key to accelerating biology research and improving pathology clinical pathways. High magnification objectives with large numerical apertures are usually preferred to resolve the fine structural details of biological samples, but they have a very limited depth-of-field. Depending on the thickness of the sample, analysis of specimens typically requires the acquisition of multiple images at different focal planes for each field-of-view, followed by the fusion of these planes into an extended depth-of-field image. This translates into low scanning speeds, increased storage space, and processing time not suitable for high-throughput clinical use. We introduce a novel content-aware multi-focus image fusion approach based on deep learning which extends the depth-of-field of high magnification objectives effectively. We demonstrate the method with three examples, showing that highly accurate, detailed, extended depth of field images can be obtained at a lower axial sampling rate, using 2-fold fewer focal planes than normally required.