bluuebunny/crossref_metadata_2025 huggingface dataset:
RRM2 expression in different molecular subtypes of breast cancer and its prognostic significance
Authors: Abdel-Rahman Manar Ahmed , Mahfouz Mena , Habashy Hany Onsy
Published: January 2022

Background

Breast cancer is one of the most common types of cancer. Ribonucleotide reductase (RNR) is a heterodimeric tetramer consisting of two Ribonucleoside-diphosphate reductase large subunits (RRM1) and two Ribonucleoside-diphosphate reductase small subunits (RRM2). RRM2 is the building subunit of RNR that is important for synthesis of Deoxynucleoside triphosphate (dNTP) during S phase of cell cycle during DNA replication. RRM2 is associated with poor prognosis in lung and colorectal cancer. In breast cancer, increased RRM2 protein level is strongly correlated with large tumour size, positive lymph node and relapse. In this study, we aimed to study expression of RRM2 in breast cancer and to correlate it with different clinicopathological parameters in Egyptian women.

Material and methods

This study was performed by investigating RRM2 protein expression in breast cancer and correlating the results with other clinicopathological variables using immunohistochemistry and tissue microarrays.

Results

About 77% of cases were RRM2 positive. High Ki67 was observed in cases with high RRM2 score. The majority of non-luminal cases expressed RRM2, however this was statistically insignificant. In ER positive group, RRM2 expression was associated with shorter disease free survival with borderline significance.

Conclusion

RRM2 protein expression can help in evaluating outcome of breast cancer patients and could be a potential therapeutic target.
Application of decellularized bone matrix as a bioscaffold in bone tissue engineering
Authors: Amirazad Halimeh , Dadashpour Mehdi , Zarghami Nosratollah
Published: January 2022

Autologous bone grafts are commonly used as the gold standard to repair and regenerate diseased bones. However, they are strongly associated with postoperative complications, especially at the donor site, and increased surgical costs. In an effort to overcome these limitations, tissue engineering (TE) has been proposed as an alternative to promote bone repair. The successful outcome of tissue engineering depends on the microstructure and composition of the materials used as scaffold. Decellularized bone matrix-based biomaterials have been applied as bioscaffolds in bone tissue engineering. These biomaterials play an important role in providing the mechanical and physical microenvironment needed by cells to proliferate and survive. Decellularized extracellular matrix (dECM) can be used as a powder, hydrogel and electrospun scaffolds. These bioscaffolds mimic the native microenvironment due to their structure similar to the original tissue. The aim of this review is to highlight the bone decellularization techniques. Herein we discuss: (1) bone structure; (2) properties of an ideal scaffold; (3) the potential of decellularized bone as bioscaffolds; (4) terminal sterilization of decellularized bone; (5) cell removing confirmation in decellularized tissues; and (6) post decellularization procedures. Finally, the improvement of bone formation by dECM and the immunogenicity aspect of using the decellularized bone matrix are presented, to illustrate how novel dECM-based materials can be used as bioscaffold in tissue engineering. A comprehensive understanding of tissue engineering may allow for better incorporation of therapeutic approaches in bone defects allowing for bone repair and regeneration.
Identification of asymptomatic Leishmania infections: a scoping review
Authors: Ibarra-Meneses Ana Victoria , Corbeil Audrey , Wagner Victoria , Onwuchekwa Chukwuemeka , Fernandez-Prada Christopher
Published: January 2022

Background

Asymptomatic Leishmania infection may play an important role in the transmission of the parasite in endemic areas. At present there is no consensus on the definition of asymptomatic Leishmania infection, nor is there a safe and accessible gold standard test for its identification.

Methods

This paper presents a scoping review to summarize definitions of asymptomatic Leishmania infection found in the literature, as well as to detail the approach (molecular, serological, cellular, and/or parasitological tests) used by researchers to identify this asymptomatic population. A scoping review of published and gray literature related to asymptomatic Leishmania infection was conducted; retrieved citations were screened based on predefined eligibility criteria, and relevant data items were extracted from eligible articles. The analysis is descriptive and is presented using tables, figures, and thematic narrative synthesis.

Results

We conducted a screening of 3008 articles, of which 175 were selected for the full review. Of these articles, we selected 106 that met the inclusion criteria. These articles were published between 1991 and 2021, and in the last 5 years, up to 38 articles were reported. Most of the studies were conducted in Brazil (26%), Spain (14%), India (12%), Bangladesh (10%), and Ethiopia (7%). Of the studies, 84.9% were conducted in the immunocompetent population, while 15.1% were conducted in the immunosuppressed population (HIV, immunosuppressive drugs, and organ transplantation population). We report 14 different techniques and 10 strategies employed by researchers to define asymptomatic Leishmania infection in an endemic area.

Conclusions

The definition of asymptomatic Leishmania infection is not unified across the literature, but often includes the following criteria: residence (or extended stay) in a Leishmania-endemic area, no reported signs/symptoms compatible with leishmaniasis, and positive on a combination of serological, molecular, cellular, and/or parasitological tests. Caution is recommended when comparing results of different studies on the subject of asymptomatic infections, as the reported prevalence cannot be confidently compared between areas due to the wide variety of tests employed by research groups. More research on the importance of asymptomatic immunosuppressed and immunocompetent Leishmania-positive populations in leishmaniasis epidemiology is required.

Graphical Abstract
The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis
Authors: Yu Tingfeng , Wu Yaxian , Liu Jia , Zhuang Yanyan , Jin Xiaoyan , Wang Lingyun
Published: January 2022

Background

The relationship between IgG4-related disease (IgG4-RD) and the risk of malignancy is still controversial. This article focused on assessing the risk of cancer in patients with IgG4-RD by meta-analysis.

Methods

We conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (pancreas, lung, gastric and lymphoma) in patients with IgG4-RD. A search from 2003 to 2020 was performed using specified terms from PubMed, Embase, Web of Science and SinoMed. Random-effects model analysis was used to pool standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to clarify the heterogeneity of the included studies. Begg’s funnel plot and Egger’s linear regression test were used to evaluate the bias of the meta-analysis. A P value < 0.05 indicated the existence of publication bias.

Results

A total of 10 studies were included in the article. The overall SIR estimates suggested an increased risk of overall cancer in IgG4-RD patients (SIR 2.57 95% CI 1.72–3.84) compared with the general population. The specific SIRs for pancreas and lymphoma were higher than those of the general population in IgG4-RD patients (SIR 4.07 95% CI 1.04–15.92, SIR 69.17 95% CI 3.91–1223.04, respectively). No significant associations were revealed in respiratory and gastric cancer (SIR 2.14 95% CI 0.97–4.75, SIR 0.95 95% CI 0.24–3.95, respectively). Four studies were found to be the major sources of heterogeneity by sensitivity analysis. There was no evidence of publication bias via Egger’s test.

Conclusion

Compared with the general population, patients with IgG4-RD appear to have a higher risk of overall cancer, especially pancreatic and lymphoma. The risk of lung and gastric cancer was not different between IgG4-RD patients and the general population.
Electroplated core–shell nanowire network electrodes for highly efficient organic light-emitting diodes
Authors: Kang Hyungseok , Kim Joo Sung , Choi Seok-Ryul , Kim Young-Hoon , Kim Do Hwan , Kim Jung-Gu , Lee Tae-Woo , Cho Jeong Ho
Published: January 2022

In this study, we performed metal (Ag, Ni, Cu, or Pd) electroplating of core–shell metallic Ag nanowire (AgNW) networks intended for use as the anode electrode in organic light-emitting diodes (OLEDs) to modify the work function (WF) and conductivity of the AgNW networks. This low-cost and facile electroplating method enabled the precise deposition of metal onto the AgNW surface and at the nanowire (NW) junctions. AgNWs coated onto a transparent glass substrate were immersed in four different metal electroplating baths: those containing AgNO3for Ag electroplating, NiSO4for Ni electroplating, Cu2P2O7for Cu electroplating, and PdCl2for Pd electroplating. The solvated metal ions (Ag+, Ni2+, Cu2+, and Pd2+) in the respective electroplating baths were reduced to the corresponding metals on the AgNW surface in the galvanostatic mode under a constant electric current achieved by linear sweep voltammetry via an external circuit between the AgNW networks (cathode) and a Pt mesh (anode). The amount of electroplated metal was systematically controlled by varying the electroplating time. Scanning electron microscopy images showed that the four different metals (shells) were successfully electroplated on the AgNWs (core), and the nanosize-controlled electroplating process produced metal NWs with varying diameters, conductivities, optical transmittances, and WFs. The metal-electroplated AgNWs were successfully employed as the anode electrodes of the OLEDs. This facile and low-cost method of metal electroplating of AgNWs to increase their WFs and conductivities is a promising development for the fabrication of next-generation OLEDs.
Regulatory modules mediating the complex neural expression patterns of the homeobrain gene during Drosophila brain development
Authors: Hildebrandt Kirsten , Kolb Dieter , Klöppel Christine , Kaspar Petra , Wittling Fabienne , Hartwig Olga , Federspiel Jannic , Findji India , Walldorf Uwe
Published: January 2022

Background

The homeobox genehomeobrain(hbn) is located in the 57B region together with two other homeobox genes,Drosophila Retinal homeobox(DRx) andorthopedia(otp). All three genes encode transcription factors with important functions in brain development.Hbnmutants are embryonic lethal and characterized by a reduction in the anterior protocerebrum, including the mushroom bodies, and a loss of the supraoesophageal brain commissure.

Results

In this study we conducted a detailed expression analysis of Hbn in later developmental stages. In the larval brain, Hbn is expressed in all type II lineages and the optic lobes, including the medulla and lobula plug. The gene is expressed in the cortex of the medulla and the lobula rim in the adult brain. We generated a new hbnKOGal4enhancer trap strain by reintegrating Gal4 in thehbnlocus through gene targeting, which reflects the completehbnexpression during development. Eight different enhancer-Gal4 strains covering 12 kb upstream ofhbn, the two large introns and 5 kb downstream of the gene, were established andhbnexpression was investigated. We characterized several enhancers that drive expression in specific areas of the brain throughout development, from embryo to the adulthood. Finally, we generated deletions of four of these enhancer regions through gene targeting and analysed their effects on the expression and function ofhbn.

Conclusion

The complex expression of Hbn in the developing brain is regulated by several specific enhancers within thehbnlocus. Each enhancer fragment driveshbnexpression in several specific cell lineages, and with largely overlapping patterns, suggesting the presence of shadow enhancers and enhancer redundancy. Specific enhancer deletion strains generated by gene targeting display developmental defects in the brain. This analysis opens an avenue for a deeper analysis ofhbnregulatory elements in the future.
Reviews
Authors: Green William
Published: January 2022

Exploiting Seismic Waveforms: Correlation, Heterogeneity and Inversion, by Brian L. N. Kennett and Andreas Fichtner, ISBN 978-1-108-82878-9, 2021, Cambridge University Press, 502 p. Hyperspectral Remote Sensing: Theory and Applications, by Prem Chandra Pandey et al., ISBN 978-0-081-02894-0, 2020, Elsevier, 506 p.
Chasm Between Cancer Quality Measures and Electronic Health Record Data Quality
Authors: Schorer Anna E. , Moldwin Richard , Koskimaki Jacob , Bernstam Elmer V. , Venepalli Neeta K. , Miller Robert S. , Chen James L.
Published: January 2022

PURPOSE

The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) requires eligible clinicians to report clinical quality measures (CQMs) in the Merit-Based Incentive Payment System (MIPS) to maximize reimbursement. To determine whether structured data in electronic health records (EHRs) were adequate to report MIPS CQMs, EHR data aggregated by ASCO's CancerLinQ platform were analyzed.

MATERIALS AND METHODS

Using the CancerLinQ health technology platform, 19 Oncology MIPS (oMIPS) CQMs were evaluated to determine the presence of data elements (DEs) necessary to satisfy each CQM and the DE percent population with patient data (fill rates). At the time of this analysis, the CancerLinQ network comprised 63 active practices, representing eight different EHR vendors and containing records for more than 1.63 million unique patients with one or more malignant neoplasms (1.73 million cancer cases).

RESULTS

Fill rates for the 63 oMIPS-associated DEs varied widely among the practices. The average site had at least one filled DE for 52% of the DEs. Only 35% of the DEs were populated for at least one patient record in 95% of the practices. However, the average DE fill rate of all practices was 23%. No data were found at any practice for 22% of the DEs. Since any oMIPS CQM with an unpopulated DE component resulted in an inability to compute the measure, only two (10.5%) of the 19 oMIPS CQMs were computable for more than 1% of the patients.

CONCLUSION

Although EHR systems had relatively high DE fill rates for some DEs, underfilling and inconsistency of DEs in EHRs render automated oncology MIPS CQM calculations impractical.
Radiation and Systemic Therapy for Limited-Stage Small-Cell Lung Cancer
Authors: Bogart Jeffrey A. , Waqar Saiama N. , Mix Michael D.
Published: January 2022

Progress in the overall treatment of small-cell lung cancer (SCLC) has moved at a slower pace than non–small-cell lung cancer. In fact, the standard treatment regimen for limited stage SCLC has not appreciably shifted in more than 20 years, consisting of four to six cycles of cisplatin and etoposide chemotherapy concurrent with thoracic radiotherapy (TRT) followed by prophylactic cranial irradiation (PCI) for responsive disease. Nevertheless, long-term outcomes have improved with median survival approaching 25-30 months, and approximately one third of patients now survive 5 years. This is likely attributable in part to improvements in staging, including use of brain magnetic resonance imaging and fluorodeoxyglucose–positron emission tomography imaging, advances in radiation treatment planning, and supportive care. The CONVERT and CALGB 30610 phase III trials failed to demonstrate a survival advantage for high-dose, once-daily TRT compared with standard 45 Gy twice-daily TRT, although high-dose, once-daily TRT remains common in practice. A phase III comparison of high-dose 60 Gy twice-daily TRT versus 45 Gy twice-daily TRT aims to confirm the provocative outcomes reported with 60 Gy twice daily in the phase II setting. Efforts over time have shifted from intensifying PCI, to attempting to reduce treatment-related neurotoxicity, to more recently questioning whether careful magnetic resonance imaging surveillance may obviate the routine need for PCI. The addition of immunotherapy has resulted in mixed success in extensive-stage SCLC with modest benefit observed with programmed death-ligand 1 inhibitors, and several ongoing trials assess programmed death-ligand 1 inhibition concurrent or adjuvant to chemoradiotherapy in limited-stage SCLC. Major advances in future treatment will likely depend on a better understanding and exploiting of molecular characteristics of SCLC with increasing personalization of therapy.
Systemic and Radiation Therapy Approaches for Locally Advanced Non–Small-Cell Lung Cancer
Authors: Higgins Kristin A. , Puri Sonam , Gray Jhanelle E.
Published: January 2022

The treatment for locally advanced non–small-cell lung cancer has changed dramatically over the past several years, with consolidative immunotherapy after concurrent chemoradiation becoming the new standard of care. Five-year survival outcomes have substantially improved with this approach. Despite these advances, further improvements are needed as the majority of patients ultimately develop progression of disease. The next-generation immunotherapy trials are currently being conducted that include approaches such as concurrent immunotherapy and addition of other therapeutic agents in the concurrent and consolidative settings. Specific unmet needs continue to exist for patients who develop disease progression after concurrent chemoradiation and immunotherapy, as well as defining the best treatment for patients with driver mutations. Future directions also include refinement of radiation techniques to reduce toxicities as much as possible, as well as the use of circulating tumor DNA in the surveillance setting. The current scientific landscape shows promising approaches that may further improve outcomes for patients with locally advanced non–small-cell lung cancer.
Extensive-Stage Small-Cell Lung Cancer: First-Line and Second-Line Treatment Options
Authors: Zugazagoitia Jon , Paz-Ares Luis
Published: January 2022

Extensive-stage small-cell lung cancer is a therapeutically challenging disease. After more than two decades without clinical progress, the addition of programmed cell death protein 1 axis blockade to platinum-based chemotherapy has demonstrated sustained overall survival benefit and represents the current standard of care in the first-line setting. Despite this benefit, resistance emerges relatively rapidly in virtually all patients. Although newer treatments are being incorporated in the relapse setting, marked therapeutic resistance is typically observed in patients with relapsed small-cell lung cancer (SCLC), underscoring the need of developing more effective therapies in this setting. Notably, recent progress in the understanding of the molecular biology of SCLC might bring possibilities toward molecularly informed therapeutic strategies for patients with SCLC, which could have a significant impact for improving outcomes in this disease. Here, we review current treatment options and recent progress made in the first-line and relapsed SCLC, including the role of biomarkers and new evolving therapeutic strategies.
Circulating Tumor DNA Minimal Residual Disease Detection of Non–Small-Cell Lung Cancer Treated With Curative Intent
Authors: Pellini Bruna , Chaudhuri Aadel A.
Published: January 2022

Circulating tumor DNA (ctDNA) minimal residual disease (MRD) is a powerful biomarker with the potential to improve survival outcomes for non–small-cell lung cancer (NSCLC). Multiple groups have shown the ability to detect MRD following curative-intent NSCLC treatment using next-generation sequencing–based assays of plasma cell-free DNA. These studies have been modest in size, largely retrospective, and without thorough prospective clinical validation. Still, when restricting measurement to the first post-treatment timepoint to assess the clinical performance of ctDNA MRD detection, they have demonstrated sensitivity for predicting disease relapse ranging between 36% and 100%, and specificity ranging between 71% and 100%. When considering all post-treatment follow-up timepoints (surveillance), including those beyond the initial post-treatment measurement, these assays' performances improve with sensitivity and specificity for identifying relapse ranging from 82% to 100% and 70% to 100%, respectively. In this manuscript, we review the evidence available to date regarding ctDNA MRD detection in patients with NSCLC undergoing curative-intent treatment and the ongoing prospective studies involving ctDNA MRD detection in this patient population.
Relationships between calciemia and calciuria and EEG and HRV parameters in patients with chronic pyelonephritis
Authors: Gozhenko Anatoliy , Kushneruk Anatoliy , Zukow Walery , Popovych Igor
Published: January 2022

Background. This article launches a new project "Relationships between parameters of electrolytes exchange and EEG&HRV in people without kidney disease and patients with chronic pyelonephritis". Calcium was chosen as the first swallow. Material and methods. The object of observation were 48 males and 15 females 24-76 years old, who came to the spa Truskavets’ (Ukraine) for the treatment of chronic pyelonephritis in remission. We recorded simultaneosly EEG (“NeuroCom Standard”) and electrocardiogram ("CardioLab+HRV") in II lead to assess the parameters of HRV. Calcium and creatinine concentration was determined in blood plasma and daily urine. Results. The observed sample is characterized by moderate and mild expressed urinary syndrome, ie represents the urological contingent of the Truskavets’ spa. It was stated normal or moderately reduced plasma calcium levels in combination with a very wide range of calcium urinary excretion. A very strong canonical correlation was found between calciumemia and EEG/HRV parameters (r=0,910). The correlation with the parameters of the beta rhythm of the EEG and VLF/ULF components of the HRV is positive, while with the parameters of the alpha rhythm of the EEG is negative. The canonical correlation between calciumuria and EEG/HRV parameters is moderate (r=0,571). There was a positive correlation with other parameters of the beta rhythm of the EEG and a negative correlation with the parameters of the delta rhythm of the EEG and LF/VLF components of HRV. Conclusion. Parameters of calcium exchange and EEG/HRV are closely related, however the question of the causal nature of correlations remains open.
Quality of life of women after mastectomy
Authors: Konieczny Magdalena
Published: January 2022

Streszczenie

Wprowadzenie. Wystąpienie choroby nowotworowej piersi u kobiety jest kryzysowym wydarzeniem,  które wiąże się z koniecznością wdrożenia długotrwałego i obciążającego leczenia. Jakość życia kobiet będących w takiej sytuacji ulega zmianie. Z tego względu bardzo ważna jest ocena kondycji psychicznej, stanu emocjonalnego kobiet oraz stopnia zaakceptowania  przez nie nowej sytuacji, a także rozpoznanie oczekiwań i potrzeb pacjentek z rakiem piersi.

Celem pracy była ocena jakości życia kobiet z rozpoznanym rakiem piersi, u których przeprowadzono zabieg mastektomii.

Materiał i metody. Badania przeprowadzono w Podkarpackim Ośrodku Onkolo­gicz­nym w Brzozowie wśród 231 kobiet z rakiem piersi, u których zastosowano leczenie chirurgiczne (mastektomia). Badania przeprowadzono za pomocą sondażu diagnostycznego przy wykorzystaniu autorskiego kwestionariusza ankiety składającego się z 39 pytań. Na przeprowadzanie badań uzyskano zgodę Dyrektora Szpitala oraz Komisji Bioetycznej.

Wyniki. Stan emocjonalny badanych został oceniony jako zły (26,9%) lub raczej zły (21,3%), a jedna trzecia respondentek odczuwała smutek i apatię (bardzo często – 26,9%; codziennie-6,8%). Kobiety najczęściej obawiały się przerzutów nowotworu (47,2%), nawrotu choroby (33,3%) oraz wystąpienia bólu (29,0%). Jako  ograniczenia życia codziennego wynikające z choroby kobiety w większości uznawały zakłócenia w życiu rodzinnym i towarzyskim (38,3%) oraz zmniejszenie efektywności pracy (30,6%).

Wnioski. Kobiety posiadały obniżoną jakość życia, w szczególności w sferze emocjonalnej, życia rodzinnego i zawodowego. Respondentki z rakiem piersi oczekują większego wsparcia ze strony lekarza, co może  stanowić podstawę do  wprowadzenia zmian w  kształceniu studentów medycyny i prowadzeniu szkolenia podyplomowego w tym zakresie.

Słowa kluczowe: rak piersi, jakość życia, mastektomia, życie rodzinne i zawodowe
Designing Entry Strategies for Subscription Platforms
Authors: Gal-Or Esther , Shi Qiaoni
Published: January 2022

We consider a subscription platform that offers services to variety-seeking consumers who incorporate transportation costs in their decision of how many and which vendor services to consume. ClassPass in fitness and MoviePass in entertainment are examples of such platforms. We find that for the platform to be successful, it should enter markets where consumers’ added benefit from patronizing more than one vendor is relatively high, thus strengthening the position of the platform in negotiations with the vendors. As well, managers should consider entering markets where competition between the vendors is relatively weak and in particular, where vendors benefit from local monopoly positions because of high transportation costs incurred by consumers. When entering such markets, offering the subscription contract is likely to attract new customers who are not active when the platform does not exist. Moreover, appropriate crafting of the agreement with the vendors in this case allows the parties to fully extract the surplus derived by platform customers. Last, the platform’s managers should be cognizant of the need to identify tools that facilitate alleviated price competition with vendors. Negotiating over an appropriate transfer fee per customer to pay the vendor or imposing restrictions on the level of service that their customers can use may be such tools. Offering customers lower-quality services when using the vendor in comparison with the quality they could obtain by buying directly from him may not be a successful tool to alleviate price competition.

This paper was accepted by Duncan Simester, marketing.
Healthcare leadership development during a pandemic: do not stop, adapt
Authors: McKimm Judy , Johnstone David , Mills Chloe , Hassanien Mohammed , Al-Hayani Abdulmonem
Published: January 2022

Research carried out in 2016 by two of the authors of this article investigated the role that leadership ‘theory’ plays within an individual's leadership development and identified other components of clinical leadership programmes that are key to enabling the development of future leaders. While early career doctors identified leadership theories and concepts as important within their development as clinical leaders, these must be closely tied to real-life practices and coupled with activities that aim to develop an increased self-awareness, understanding of others, clinical exposure and leadership tools that they can use in practice. During a healthcare crisis, such as a global pandemic, maintaining a focus on leadership development (particularly for more junior clinicians) might not be seen as important, but leadership is needed to help people and organisations ‘get through’ a crisis as well as help develop leadership capacity for the longer term. This article, drawing from contemporary literature, the authors' own research and reflections, discusses how leadership development needs to continually adapt to meet new demands and sets out tips for those involved with clinical leadership development.
Hybrid CTC-Attention Network-Based End-to-End Speech Recognition System for Korean Language
Authors: Park Hosung , Kim Changmin , Son Hyunsoo , Seo Soonshin , Kim Ji-Hwan
Published: January 2022

In this study, an automatic end-to-end speech recognition system based on hybrid CTC-attention network for Korean language is proposed. Deep neural network/hidden Markov model (DNN/HMM)-based speech recognition system has driven dramatic improvement in this area. However, it is difficult for non-experts to develop speech recognition for new applications. End-to-end approaches have simplified speech recognition system into a single-network architecture. These approaches can develop speech recognition system that does not require expert knowledge. In this paper, we propose hybrid CTC-attention network as end-to-end speech recognition model for Korean language. This model effectively utilizes a CTC objective function during attention model training. This approach improves the performance in terms of speech recognition accuracy as well as training speed. In most languages, end-to-end speech recognition uses characters as output labels. However, for Korean, character-based end-to-end speech recognition is not an efficient approach because Korean language has 11,172 possible numbers of characters. The number is relatively large compared to other languages. For example, English has 26 characters, and Japanese has 50 characters. To address this problem, we utilize Korean 49 graphemes as output labels. Experimental result shows 10.02% character error rate (CER) when 740 hours of Korean training data are used.
Immunogenicity and safety of adenovirus-based vector vaccines for COVID-19: a systematic review and meta-analysis
Authors: Kalaij Ayers Gilberth Ivano , Dirjayanto Valerie Josephine , Yusuf Syarif Maulana , Nelwan Erni Juwita
Published: January 2022

BACKGROUND Despite various research on vaccine development, severe acute respiratory syndrome coronavirus 2 infection continues to spread. Thus, developing a more effective vaccine for production and clinical efficacy is still in high demand. This review aimed to assess the immunogenicity and safety of adenovirus-based vector vaccine (Ad-vaccines) including Ad5-vectored, ChAdOx1 nCoV-19, rAd26-S or rAd5-S, and Ad26.COV2.S as the promising solutions for COVID-19.

METHODS We conducted a systematic review and meta analysis of clinical trials based on the preferred reporting items for systematic reviews and meta-analyses guidelines through PubMed, Scopus, Cochrane, and EBSCOhost until August 17, 2021. We implemented inclusion and exclusion criteria and assessed the studies using OHAT risk of bias rating tool for human and animal studies. Pooled estimates of odds ratio (OR) were analyzed using fixed-effect model.

RESULTS This systematic review yielded 12 clinical studies with a total of 75,105 subjects. Although the studies were heterogeneous, this meta-analysis showed that Ad-vaccine significantly increased protection and immune response against COVID-19 with a pooled efficacy of 84.68% compared to placebo (p<0.00001). Forest plot also indicated that Ad-vaccine conferred protection against moderate to severe COVID-19 with a pooled OR of 0.26 (p<0.00001). Ad-vaccine had also shown a good safety profile with local site pain and fever as the most common side effects.

CONCLUSIONS Ad-vaccine had shown a good immunogenicity for COVID-19 with a good pooled efficacy and was proven safe for COVID-19 patients.
Chromatic confocal measurement method using a phase Fresnel zone plate
Authors: Liu Tao , Wang Jiayi , Liu Qiang , Hu Jiaqi , Wang Zhibin , Wan Chao , Yang Shuming
Published: January 2022

A chromatic confocal measurement method based on a phase Fresnel zone plate (FZP) is described. Strong dispersion of FZP results in significant axial focal shift. The axial dispersion curve is close to linear within a certain wavelength range determined by the quantitative calculation using the vectorial angular spectrum theory. A 11.27 mm diameter phase FZP with a primary focal length of 50 mm was processed using standard photolithography technology and used as the dispersive objective in a homemade chromatic confocal measurement system. The calibrated axial measurement range exceeds 16 mm, the axial resolution reaches 0.8 µm, and the measurement accuracy of displacement is better than 0.4%. This chromatic confocal sensor has been practically used in the measurement of step height, glass thickness, and 3D surface profile. The proposed method has the obvious characteristics of simplicity, greatly reduced cost and superior performance. It is believed that this sensing method has broad application prospects in glass, coating, machinery, electronics, optics and other industries.
Evolutionary plasticity and functional versatility of CRISPR systems
Authors: Koonin Eugene V. , Makarova Kira S.
Published: January 2022

The principal biological function of bacterial and archaeal CRISPR systems is RNA-guided adaptive immunity against viruses and other mobile genetic elements (MGEs). These systems show remarkable evolutionary plasticity and functional versatility at multiple levels, including both the defense mechanisms that lead to direct, specific elimination of the target DNA or RNA and those that cause programmed cell death (PCD) or induction of dormancy. This flexibility is also evident in the recruitment of CRISPR systems for nondefense functions. Defective CRISPR systems or individual CRISPR components have been recruited by transposons for RNA-guided transposition, by plasmids for interplasmid competition, and by viruses for antidefense and interviral conflicts. Additionally, multiple highly derived CRISPR variants of yet unknown functions have been discovered. A major route of innovation in CRISPR evolution is the repurposing of diverged repeat variants encoded outside CRISPR arrays for various structural and regulatory functions. The evolutionary plasticity and functional versatility of CRISPR systems are striking manifestations of the ubiquitous interplay between defense and “normal” cellular functions.
Prioritizing public health? Factors affecting the issuance of stay-at-home orders in response to COVID-19 in Africa
Authors: Murray Gregg R. , Rutland Joshua
Published: January 2022

COVID-19 has sickened and killed millions of people globally. Conventional non-pharmaceutical interventions, particularly stay-at-home orders (SAHOs), though effective for limiting the spread of disease have significantly disrupted social and economic systems. The effects also have been dramatic in Africa, where many states are already vulnerable due to their developmental status. This study is designed to test hypotheses derived from the public health policymaking literature regarding the roles played by medical and political factors as well as social, economic, and external factors in African countries’ issuance of SAHOs in response to the early stages of the COVID-19 pandemic. Using event history analysis, this study analyzed these five common factors related to public health policy to determine their impact on African states’ varying decisions regarding the issuance of SAHOs. The results of this analysis suggest that medical factors significantly influenced decisions as did factors external to the states, while the role of political factors was limited. Social and economic factors played no discernible role. Overall, this study suggests how African leaders prioritized competing factors in the early stages of a public health crisis.
Use of open-text responses to recode categorical survey data on postpartum contraception use among women in the United States: A mixed-methods inquiry of Pregnancy Risk Assessment Monitoring System data
Authors: Richards Nicole K. , Morley Christopher P. , Wojtowycz Martha A. , Bevec Erin , Levandowski Brooke A.
Published: January 2022

Background

Postpartum contraception prevents unintended pregnancies and short interpregnancy intervals. The Pregnancy Risk Assessment Monitoring System (PRAMS) collects population-based data on postpartum contraception nonuse and reasons for not using postpartum contraception. In addition to quantitative questions, PRAMS collects open-text responses that are typically left unused by secondary quantitative analyses. However, abundant preexisting open-text data can serve as a resource for improving quantitative measurement accuracy and qualitatively uncovering unexpected responses. We used PRAMS survey questions to explore unprompted reasons for not using postpartum contraception and offer insight into the validity of categorical responses.

Methods and findings

We used 31,208 categorical 2012 PRAMS survey responses from postpartum women in the US to calculate original prevalences of postpartum contraception use and nonuse and reasons for contraception nonuse. A content analysis of open-text responses systematically recoded data to mitigate survey bias and ensure consistency, resulting in adjusted prevalence calculations and identification of other nonuse themes. Recoded contraception nonuse slightly differed from original reports (21.5% versus 19.4%). Both calculations showed that many respondents reporting nonuse may be at a low risk for pregnancy due to factors like tubal ligation or abstinence. Most frequent nonuse reasons were not wanting to use birth control (27.1%) and side effect concerns (25.0%). Other open-text responses showed common themes of infertility, and breastfeeding as contraception. Comparing quantitative and qualitative responses revealed contradicting information, suggesting respondent misinterpretation and confusion surrounding the term “pregnancy prevention.” Though this analysis may be limited by manual coding error and researcher biases, we avoided coding exhaustion via 1-hour coding periods and validated reliability through intercoder kappa scores.

Conclusions

In this study, we observed that respondents reporting contraception nonuse often described other methods of pregnancy prevention and contraception barriers that were not included in categorical response options. Open-text responses shed light on a more comprehensive list of pregnancy prevention methods and nonuse options. Our findings contribute to survey questions that can lead to more accurate depiction of postpartum contraceptive behavior. Additionally, future use of these qualitative methods may be used to improve other health behavior survey development and resulting data.
Coupled exoskeleton assistance simplifies control and maintains metabolic benefits: A simulation study
Authors: Bianco Nicholas A. , Franks Patrick W. , Hicks Jennifer L. , Delp Scott L.
Published: January 2022

Assistive exoskeletons can reduce the metabolic cost of walking, and recent advances in exoskeleton device design and control have resulted in large metabolic savings. Most exoskeleton devices provide assistance at either the ankle or hip. Exoskeletons that assist multiple joints have the potential to provide greater metabolic savings, but can require many actuators and complicated controllers, making it difficult to design effective assistance. Coupled assistance, when two or more joints are assisted using one actuator or control signal, could reduce control dimensionality while retaining metabolic benefits. However, it is unknown which combinations of assisted joints are most promising and if there are negative consequences associated with coupled assistance. Since designing assistance with human experiments is expensive and time-consuming, we used musculoskeletal simulation to evaluate metabolic savings from multi-joint assistance and identify promising joint combinations. We generated 2D muscle-driven simulations of walking while simultaneously optimizing control strategies for simulated lower-limb exoskeleton assistive devices to minimize metabolic cost. Each device provided assistance either at a single joint or at multiple joints using massless, ideal actuators. To assess if control could be simplified for multi-joint exoskeletons, we simulated different control strategies in which the torque provided at each joint was either controlled independently or coupled between joints. We compared the predicted optimal torque profiles and changes in muscle and total metabolic power consumption across the single joint and multi-joint assistance strategies. We found multi-joint devices–whether independent or coupled–provided 50% greater metabolic savings than single joint devices. The coupled multi-joint devices were able to achieve most of the metabolic savings produced by independently-controlled multi-joint devices. Our results indicate that device designers could simplify multi-joint exoskeleton designs by reducing the number of torque control parameters through coupling, while still maintaining large reductions in metabolic cost.
Impact of procedural variability and study design quality on the efficacy of cell-based therapies for heart failure - a meta-analysis
Authors: Xu Zhiyi , Neuber Sebastian , Nazari-Shafti Timo , Liu Zihou , Dong Fengquan , Stamm Christof
Published: January 2022

Background

Cell-based therapy has long been considered a promising strategy for the treatment of heart failure (HF). However, its effectiveness in the clinical setting is now doubted. Because previous meta-analyses provided conflicting results, we sought to review all available data focusing on cell type and trial design.

Methods and findings

The electronic databases PubMed, Cochrane library, ClinicalTrials.gov, and EudraCT were searched for randomized controlled trials (RCTs) utilizing cell therapy for HF patients from January 1, 2000 to December 31, 2020. Forty-three RCTs with 2855 participants were identified. The quality of the reported study design was assessed by evaluating the risk-of-bias (ROB). Primary outcomes were defined as mortality rate and left ventricular ejection fraction (LVEF) change from baseline. Secondary outcomes included both heart function data and clinical symptoms/events. Between-study heterogeneity was assessed using the I2 index. Subgroup analysis was performed based on HF type, cell source, cell origin, cell type, cell processing, type of surgical intervention, cell delivery routes, cell dose, and follow-up duration. Only 10 of the 43 studies had a low ROB for all method- and outcome parameters. A higher ROB was associated with a greater increase in LVEF. Overall, there was no impact on mortality for up to 12 months follow-up, and a clinically irrelevant average LVEF increase by LVEF (2.4%, 95% CI = 0.75−4.05, p = 0.004). Freshly isolated, primary cells tended to produce better outcomes than cultured cell products, but there was no clear impact of the cell source tissue, bone marrow cell phenotype or cell chricdose (raw or normalized for CD34+ cells). A meaningful increase in LVEF was only observed when cell therapy was combined with myocardial revascularization.

Conclusions

The published results suggest a small increase in LVEF following cell therapy for heart failure, but publication bias and methodologic shortcomings need to be taken into account. Given that cardiac cell therapy has now been pursued for 20 years without real progress, further efforts should not be made.

Study registry number

This meta-analysis is registered at the international prospective register of systematic reviews, number CRD42019118872.
Cost analysis of treating cardiovascular diseases in a super-specialty hospital
Authors: Kumar Atul , Siddharth Vijaydeep , Singh Soubam Iboyaima , Narang Rajiv
Published: January 2022

Cardiovascular care is expensive; hence, economic evaluation is required to estimate resources being consumed and to ensure their optimal utilization. There is dearth of data regarding cost analysis of treating various diseases including cardiac diseases from developing countries. The study aimed to analyze resource consumption in treating cardio-vascular disease patients in a super-specialty hospital. An observational and descriptive study was carried out from April 2017 to June 2018 in the Department of Cardiology, Cardio-Thoracic (CT) Centre of All India Institute of Medical Sciences, New Delhi, India. As per World Health Organization, common cardiovascular diseases i.e. Coronary Artery Disease (CAD), Rheumatic Heart Disease (RHD), Cardiomyopathy, Congenital heart diseases, Cardiac Arrhythmias etc. were considered for cost analysis. Medical records of 100 admitted patients (Ward & Cardiac Care Unit) of cardiovascular diseases were studied till discharge and number of patient records for a particular CVD was identified using prevalence-based ratio of admitted CVD patient data. Traditional Costing and Time Driven Activity Based Costing (TDABC) methods were used for cost computation. Per bed per day cost incurred by the hospital for admitted patients in Cardiac Care Unit, adult and pediatric cardiology ward was calculated to be Indian Rupee (INR) 28,144 (US$ 434), INR 22,210 (US$ 342) and INR 18,774 (US$ 289), respectively. Inpatient cost constituted almost 70% of the total cost and equipment cost accounted for more than 50% of the inpatient cost followed by human resource cost (28%). Per patient cost of treating any CVD was computed to be INR 2,47,822 (US $ 3842). Cost of treating Rheumatic Heart Disease was the highest among all CVDs followed by Cardiomyopathy and other CVDs. Cost of treating cardiovascular diseases in India is less than what has been reported in developed countries. Findings of this study would aid policy makers considering recent radical changes and massive policy reforms ushered in by the Government of India in healthcare delivery.
A 12-hospital prospective evaluation of a clinical decision support prognostic algorithm based on logistic regression as a form of machine learning to facilitate decision making for patients with suspected COVID-19
Authors: Lupei Monica I. , Li Danni , Ingraham Nicholas E. , Baum Karyn D. , Benson Bradley , Puskarich Michael , Milbrandt David , Melton Genevieve B. , Scheppmann Daren , Usher Michael G. , Tignanelli Christopher J.
Published: January 2022

Objective

To prospectively evaluate a logistic regression-based machine learning (ML) prognostic algorithm implemented in real-time as a clinical decision support (CDS) system for symptomatic persons under investigation (PUI) for Coronavirus disease 2019 (COVID-19) in the emergency department (ED).

Methods

We developed in a 12-hospital system a model using training and validation followed by a real-time assessment. The LASSO guided feature selection included demographics, comorbidities, home medications, vital signs. We constructed a logistic regression-based ML algorithm to predict “severe” COVID-19, defined as patients requiring intensive care unit (ICU) admission, invasive mechanical ventilation, or died in or out-of-hospital. Training data included 1,469 adult patients who tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) within 14 days of acute care. We performed: 1) temporal validation in 414 SARS-CoV-2 positive patients, 2) validation in a PUI set of 13,271 patients with symptomatic SARS-CoV-2 test during an acute care visit, and 3) real-time validation in 2,174 ED patients with PUI test or positive SARS-CoV-2 result. Subgroup analysis was conducted across race and gender to ensure equity in performance.

Results

The algorithm performed well on pre-implementation validations for predicting COVID-19 severity: 1) the temporal validation had an area under the receiver operating characteristic (AUROC) of 0.87 (95%-CI: 0.83, 0.91); 2) validation in the PUI population had an AUROC of 0.82 (95%-CI: 0.81, 0.83). The ED CDS system performed well in real-time with an AUROC of 0.85 (95%-CI, 0.83, 0.87). Zero patients in the lowest quintile developed “severe” COVID-19. Patients in the highest quintile developed “severe” COVID-19 in 33.2% of cases. The models performed without significant differences between genders and among race/ethnicities (all p-values > 0.05).

Conclusion

A logistic regression model-based ML-enabled CDS can be developed, validated, and implemented with high performance across multiple hospitals while being equitable and maintaining performance in real-time validation.