bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement in distal pancreatectomy for tumors in the body and tail of the pancreas
Authors: Jiang Li , Ning Deng , Chen Xiao-ping
Published: February 2021

Background

Pancreatic resections are complex and technically challenging surgical procedures. They often come with potential limitations to high-volume centers. Distal pancreatectomy is a relatively simple procedure in most cases. It facilitates the development of up-to-date minimally invasive surgical procedures in pancreatic surgery including laparoscopic distal pancreatectomy and robot-assisted distal pancreatectomy.

Main body

To obtain a desirable long-term prognosis, R0 resection and adequate lymphadenectomy are crucial to the surgical management of pancreatic cancer, and they demand standard procedure and multi-visceral resection if necessary. With respect to combined organ resection, progress has been made in evaluating and determining when and how to preserve the spleen. The postoperative pancreatic fistula, however, remains the most significant complication of distal pancreatectomy, with a rather high incidence. In addition, a safe closure of the pancreatic remnant persists as an area of concern. Therefore, much efforts that focus on the management of the pancreatic stump have been made to mitigate morbidity.

Conclusion

This review summarized the historical development of the techniques for pancreatic resections in recent years and describes the progress. The review eventually looked into the controversies regarding distal pancreatectomy for tumors in the body and tail of the pancreas.
Prevalence and significance of serum 14–3-3η in juvenile idiopathic arthritis
Authors: Reyhan Iris , Zhukov Olga S. , Lagier Robert J. , Bridgforth Robert F. , Williams Gary J. , Popov Joanna M. , Naides Stanley J. , Reiff Andreas
Published: February 2021

Background

Prompt diagnosis of juvenile idiopathic arthritis (JIA) is important to avoid long term complications. Elevated serum 14–3-3η levels improve the diagnostic sensitivity of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody in adult rheumatoid arthritis (RA), and have been associated with more severe phenotype. We investigated the prevalence and clinical significance of serum 14–3-3η in different types of JIA.

Methods

JIA patients (n = 151) followed by the Pediatric Rheumatology Core at Children’s Hospital of Los Angeles were categorized into 5 groups: polyarticular JIA RF+ (PJIA RF+; n = 39), PJIA RF- (n = 39), psoriatic arthritis (PsA; n = 19), enthesitis-related arthritis (ERA; n = 18), and oligoarticular JIA (OJIA [control group]; n = 36). RF, CCP antibody, and 14–3-3η were measured for all patients. 14–3-3η serum levels > 0.2 ng/mL were considered positive. Disease activity was assessed by the Juvenile Arthritis Disease Activity Score-71 (JADAS-71).

Results

Elevated 14–3-3η levels were detected in 34/151 (23%) patients, and across all groups tested. Most patients with 14–3-3η had titers ≥4 times above the cutoff value. The majority (22, 65%) of 14–3-3η-positive patients were also positive for RF or CCP antibodies, 16 (47%) were positive for all 3, and 12 (35%) were single-positive for 14–3-3η. The highest prevalence of 14–3-3η was in PJIA RF+ patients (49%), followed by OJIA (22%). Positivity for 14–3-3η was not significantly associated with disease activity or age at diagnosis.

Conclusion

Serum 14–3-3η can be detected in all forms of JIA tested but appears to be most common in PJIA RF+. 14–3-3η does not appear to correlate with disease activity in JIA.
Disordered eating among adolescents with chronic pain: the experience of a pediatric rheumatology subspecialty pain clinic
Authors: Pianucci Lauren , Sonagra Maitry , Greenberg Brooke A. , Priestley Diana R. , Gmuca Sabrina
Published: February 2021

Background

Disordered eating and chronic pain often co-occur in adolescents, but the relationship between these conditions is not well understood. We aimed to determine the prevalence of and to identify the clinical characteristics associated with the presence of disordered eating among adolescents with chronic musculoskeletal pain (CMP) presenting to a pediatric rheumatology subspecialty pain clinic.

Methods

This was a retrospective cohort study of pediatric patients presenting to a pediatric rheumatology subspecialty pain clinic for an initial consultation from March 2018 to March 2019. We complemented data from an existing patient registry with secondary chart review for patients identified with disordered eating. We compared patient characteristics based on the presence or absence of disordered eating among adolescents with CMP. Logistic regression modeling was used to determine factors associated with disordered eating.

Results

Of the 228 patients who were seen for an initial consultation in the pain clinic in 1 year, 51 (22.4%) had disordered eating. Only eight (15.7%) of the 51 patients identified with disordered eating had a previously documented formal eating disorder diagnosis. Through multivariate logistic regression modeling, we found that disordered eating was associated with older age, higher functional disability, presence of abdominal pain, presence of gastrointestinal comorbidities, and presence of anxiety (all p < 0.05).

Conclusions

Adolescents with chronic pain, especially those who experience gastrointestinal issues, anxiety, and greater functional disability, should be evaluated for disordered eating by the treating clinician in order to ensure timely and appropriate treatment.
ATP-evoked intracellular Ca2+ transients shape the ionic permeability of human microglia from epileptic temporal cortex
Authors: Palomba Nicole Piera , Martinello Katiuscia , Cocozza Germana , Casciato Sara , Mascia Addolorata , Di Gennaro Giancarlo , Morace Roberta , Esposito Vincenzo , Wulff Heike , Limatola Cristina , Fucile Sergio
Published: February 2021

Background

Intracellular Ca2+modulates several microglial activities, such as proliferation, migration, phagocytosis, and inflammatory mediator secretion. Extracellular ATP, the levels of which significantly change during epileptic seizures, activates specific receptors leading to an increase of intracellular free Ca2+concentration ([Ca2+]i). Here, we aimed to functionally characterize human microglia obtained from cortices of subjects with temporal lobe epilepsy, focusing on the Ca2+-mediated response triggered by purinergic signaling.

Methods

Fura-2 based fluorescence microscopy was used to measure [Ca2+]iin primary cultures of human microglial cells obtained from surgical specimens. The perforated patch-clamp technique, which preserves the cytoplasmic milieu, was used to measure ATP-evoked Ca2+-dependent whole-cell currents.

Results

In human microglia extracellular ATP evoked [Ca2+]iincreases depend on Ca2+entry from the extracellular space and on Ca2+mobilization from intracellular compartments. Extracellular ATP also induced a transient fivefold potentiation of the total transmembrane current, which was completely abolished when [Ca2+]iincreases were prevented by removing external Ca2+and using an intracellular Ca2+chelator. TRAM-34, a selective KCa3.1 blocker, significantly reduced the ATP-induced current potentiation but did not abolish it. The removal of external Cl−in the presence of TRAM-34 further lowered the ATP-evoked effect. A direct comparison between the ATP-evoked mean current potentiation and mean Ca2+transient amplitude revealed a linear correlation. Treatment of microglial cells with LPS for 48 h did not prevent the ATP-induced Ca2+mobilization but completely abolished the ATP-mediated current potentiation. The absence of the Ca2+-evoked K+current led to a less sustained ATP-evoked Ca2+entry, as shown by the faster Ca2+transient kinetics observed in LPS-treated microglia.

Conclusions

Our study confirms a functional role for KCa3.1 channels in human microglia, linking ATP-evoked Ca2+transients to changes in membrane conductance, with an inflammation-dependent mechanism, and suggests that during brain inflammation the KCa3.1-mediated microglial response to purinergic signaling may be reduced.
Zika virus public health crisis and the perpetuation of gender inequality in Brazil
Authors: Coutinho Raquel Zanatta , Villanueva Aida , Weitzman Abigail , Marteleto Letícia Junqueira
Published: February 2021

Background

In 2015–2017, the Americas experienced a highly consequential epidemics for pregnancy and childbearing. Mainly transmitted by the mosquito Aedes aegypti, but also through sexual intercourse, the Zika virus poses the risk of congenital Zika syndrome to fetus, which includes microcephaly and other child development complications. When a public health crisis taps directly into reproductive health, typically a feminine realm, responses to the emergency may exacerbate deeply-rooted gender norms. This paper investigates the role of gender in two relational contexts: (a) the government-led response to the pandemic in terms of communication campaigns aimed at preventing Zika infections; and (b) an individual level of response to the emergency, concerning women’s negotiation with their sexual partners with regard to the prevention of Zika as well as pregnancies.

Methods

We conducted content analysis of 94 unique pieces from public health communication campaigns produced by governmental agencies with the goal of promoting Zika awareness. Print and online materials were collected from May 2016 to August 2017, and included TV ads, Internet Pop-ups, and pamphlets. We also analyzed transcripts from 16 focus groups conducted with reproductive-aged women (18–40) in Belo Horizonte and Recife, two large cities differently affected by the Zika outbreak. Women answered open-ended questions connected to the epidemic, in areas such as personal knowledge and experiences with the Zika virus, experiences of their friends and acquaintances, their primary information sources, their perceptions of public health efforts toward containing the outbreak, as well as women’s contraceptive use.

Results

Campaign pieces handling pregnancy and microcephaly were largely gendered. Pieces targeted women, placing on their shoulders the responsibility for protecting a potential fetus from the disease. Importantly, campaigns neglected addressing male’s participation on Zika prevention and contraceptive management, while failing to take into account Brazil’s large proportion of unplanned pregnancies. Women were placed in a double bind by being expected to prevent both pregnancy and Zika, in a context where gendered power imbalances often translate in women having little power/means for condom negotiation/avoiding unprotected sexual intercourse.

Conclusion

Government and individual responses to the epidemics reinforced gender roles, situating pregnant women as responsible for averting mosquito bites and microcephaly. Further, prevention campaigns largely excluded men. Since low-socioeconomic status women possessed fewer resources to preclude infection, we also found that beyond the gender divide, this subgroup faced more pronounced Zika prevention challenges as they found it harder to negotiate condom use with their sexual partners and often could not access other types of contraceptives resulting in unplanned pregnancies.
Impairments of cortico-cortical connectivity in fine tactile sensation after stroke
Authors: Zhou Sa , Huang Yanhuan , Jiao Jiao , Hu Junyan , Hsing Chihchia , Lai Zhangqi , Yang Yang , Hu Xiaoling
Published: February 2021

Background

Fine tactile sensation plays an important role in motor relearning after stroke. However, little is known about its dynamics in post-stroke recovery, principally due to a lack of effective evaluation on neural responses to fine tactile stimulation. This study investigated the post-stroke alteration of cortical connectivity and its functional structure in response to fine tactile stimulation via textile fabrics by electroencephalogram (EEG)-derived functional connectivity and graph theory analyses.

Method

Whole brain EEG was recorded from 64 scalp channels in 8 participants with chronic stroke and 8 unimpaired controls before and during the skin of the unilateral forearm contacted with a piece of cotton fabric. Functional connectivity (FC) was then estimated using EEG coherence. The fabric stimulation induced FC (SFC) was analyzed by a cluster-based permutation test for the FC in baseline and fabric stimulation. The functional structure of connectivity alteration in the brain was also investigated by assessing the multiscale topological properties of functional brain networks according to the graph theory.

Results

In the SFC distribution, an altered hemispheric lateralization (HL) (HL degree, 14%) was observed when stimulating the affected forearm in the stroke group, compared to stimulation of the unaffected forearm of the stroke group (HL degree, 53%) and those of the control group (HL degrees, 92% for the left and 69% for the dominant right limb). The involvement of additional brain regions, i.e., the distributed attention networks, was also observed when stimulating either limb of the stroke group compared with those of the control. Significantly increased (P < 0.05) global and local efficiencies were found when stimulating the affected forearm compared to the unaffected forearm. A significantly increased (P < 0.05) degree of inter-hemisphere FC (interdegree) mainly within ipsilesional somatosensory region and a significantly diminished degree of intra-hemisphere FC (intradegree) (P < 0.05) in ipsilesional primary somatosensory region were observed when stimulating the affected forearm, compared with the unaffected forearm.

Conclusions

The alteration of cortical connectivity in fine tactile sensation post-stroke was characterized by the compensation from the contralesional hemisphere and distributed attention networks related to involuntary attention. The interhemispheric connectivity could implement the compensation from the contralateral hemisphere to the ipsilesional somatosensory region. Stroke participants also exerted increased cortical activities in fine tactile sensation.
The yearly financing need of providing paid maternity leave in the informal sector in Indonesia
Authors: Siregar Adiatma Y. M. , Pitriyan Pipit , Hardiawan Donny , Zambrano Paul , Vilar-Compte Mireya , Belismelis Graciela Ma Teruel , Moncada Meztli , Tamayo David , Carroll Grace , Perez-Escamilla Rafael , Mathisen Roger
Published: February 2021

Background

The economic cost of not breastfeeding in Indonesia is estimated at US$1.5–9.4 billion annually, the highest in South East Asia. Half of the 33.6 million working women of reproductive age (WRA) in Indonesia (15–49 years) are informal employees, meaning they are working as casual workers or they are self-employed (small scale business) and assisted by unpaid/family worker(s). No specific maternity protection entitlements are currently available for WRA working informally in Indonesia. This study aims to estimate the financing need of providing maternity leave cash transfer (MCT) for WRA working in the informal sector in Indonesia.

Method

The costing methodology used is the adapted version of the World Bank methodology by Vilar-Compte et al, following pre-set steps to estimate costs using national secondary data. We used the 2018 Indonesian National Socio-Economic Survey to estimate the number of women working informally who gave birth within the last year. The population covered, potential cash transfer’s unitary cost, the incremental coverage of the policy in terms of time and coverage, and the administrative costs were used to estimate the cost of MCT for the informal sector.

Result

At 100% coverage for 13 weeks of leave, the yearly financing need of MCT ranged from US$175million (US$152/woman) to US$669million (US$583/woman). The share of the yearly financing need did not exceed 0.5% of Indonesian Gross Domestic Product (GDP).

Conclusions

The yearly financing need of providing MCT for eligible WRA working in the informal sector is economically attractive as it amounts to less than 0.5% of GDP nominal of Indonesia. While such a program would be perceived as a marked increase from current public health spending at the onset, such an investment could substantially contribute to the success of breastfeeding and substantial corresponding public health savings given that more than half of working Indonesian WRA are employed in the informal sector. Such policies should be further explored while taking into consideration realistic budget constraints and implementation capacity.
Applying regulatory science in traditional chinese medicines for improving public safety and facilitating innovation in China: a scoping review and regulatory implications
Authors: Liang Zuanji , Lai Yunfeng , Li Meng , Shi Junnan , Lei Chi Ieong , Hu Hao , Ung Carolina Oi Lam
Published: February 2021

Background

The National Medical Products Administration (NMPA) in China has set to advance the regulatory capacity of traditional Chinese medicines (TCMs) with the adoption of regulatory science (RS). However, the priority of actions at the interface of RS and TCMs were yet to be defined. This research aims to identify the priority areas and summarize core actions for advancing RS for traditional medicines in China.

Methods

A mixed approach of documentary analysis of government policies, regulations and official information about TCMs regulation in China, and a scoping review of literature using 4 databases (PubMed, ScienceDirect, Scopus and CNKI) on major concerns in TCMs regulation was employed.

Results

Ten priority areas in the development of TCM-related regulatory science in China have been identified, including: (1) modernizing the regulatory system with a holistic approach; (2) advancing the methodology for the quality control of TCMs; (3) fostering the control mechanism of TCMs manufacturing process; (4) improving clinical evaluation of TCMs and leveraging real world data; (5) re-evaluation of TCMs injection; (6) developing evaluation standards for classic TCMs formula; (7) harnessing diverse data to improve pharmacovigilance of TCMs; (8) evaluating the value of integrative medicine in clinical practice with scientific research; (9) advancing the regulatory capacity to encourage innovation in TCMs; and (10) advancing a vision of collaboration for RS development in TCMs.

Conclusions

RS for TCMs in China encompasses revolution of operational procedures, advancement in science and technology, and cross-disciplinary collaborations. Such experiences could be integrated in the communications among drug regulatory authorities to promote standardized and scientific regulation of traditional medicines.
Low expression of NSD1, NSD2, and NSD3 define a subset of human papillomavirus-positive oral squamous carcinomas with unfavorable prognosis
Authors: Gameiro Steven F. , Ghasemi Farhad , Zeng Peter Y. F. , Mundi Neil , Howlett Christopher J. , Plantinga Paul , Barrett John W. , Nichols Anthony C. , Mymryk Joe S.
Published: February 2021

Background

Frequent mutations in the nuclear receptor binding SET domain protein 1 (NSD1) gene have been observed in head and neck squamous cell carcinomas (HNSCC). NSD1 encodes a histone 3 lysine-36 methyltransferase. NSD1 mutations are correlated with improved clinical outcomes and increased sensitivity to platinum-based chemotherapy agents in human papillomavirus-negative (HPV-) tumors, despite weak T-cell infiltration. However, the role of NSD1 and related family members NSD2 and NSD3 in human papillomavirus-positive (HPV+) HNSCC is unclear.

Methods

Using data from over 500 HNSCC patients from The Cancer Genome Atlas (TCGA), we compared the relative level of mRNA expression of NSD1, NSD2, and NSD3 in HPV+ and HPV- HNSCC. Correlation analyses were performed between T-cell infiltration and the relative level of expression of NSD1, NSD2, and NSD3 mRNA in HPV+ and HPV- HNSCC. In addition, overall survival outcomes were compared for both the HPV+ and HPV- subsets of patients based on stratification by NSD1, NSD2, and NSD3 expression levels.

Results

Expression levels of NSD1, NSD2 or NSD3 were not correlated with altered lymphocyte infiltration in HPV+ HNSCC. More importantly, low expression of NSD1, NSD2, or NSD3 correlated with significantly reduced overall patient survival in HPV+, but not HPV- HNSCC.

Conclusion

These results starkly illustrate the contrast in molecular features between HPV+ and HPV- HNSCC tumors and suggest that NSD1, NSD2, and NSD3 expression levels should be further investigated as novel clinical metrics for improved prognostication and patient stratification in HPV+ HNSCC.
Automated detection and quantification of reverse triggering effort under mechanical ventilation
Authors: Pham Tài , Montanya Jaume , Telias Irene , Piraino Thomas , Magrans Rudys , Coudroy Rémi , Damiani L. Felipe , Mellado Artigas Ricard , Madorno Matías , Blanch Lluis , Brochard Laurent ,   the BEARDS study investigators, Pham Tài , Montanya Jaume , Telias Irene , Piraino Thomas , Magrans Rudys , Coudroy Rémi , Damiani L. Felipe , Mellado Artigas Ricard , Madorno Matías , Blanch Lluis , Brochard Laurent , Santis Cesar , Mauri Tommaso , Spinelli Elena , Grasselli Giacomo , Spadaro Savino , Volta Carlo Alberto , Mojoli Francesco , Georgopoulos Dimitris , Kondili Eumorfia , Soundoulounaki Stella , Becher Tobias , Weiler Norbert , Schaedler Dirk , Roca Oriol , Santafe Manel , Mancebo Jordi , Heunks Leo , de Vries Heder , Chen Chang-Wen , Zhou Jian-Xin , Chen Guang-Qiang , Rittayamai Nuttapol , Tiribelli Norberto , Fredes Sebastian , Mellado Artigas Ricard , Ferrando Ortolá Carlos , Beloncle François , Mercat Alain , Arnal J. M. , Diehl J. L. , Demoule A. , Dres M. , Jochmans S. , Chelly J. , Terzi Nicolas , Guérin Claude , Baedorf Kassis E. , Beitler J. , Chiumello Davide , Bolgiaghi Erica Ferrari Luca , Fanelli V. , Alphonsine J. E. , Thille Arnaud W. , Papazian Laurent
Published: February 2021

Background

Reverse triggering (RT) is a dyssynchrony defined by a respiratory muscle contraction following a passive mechanical insufflation. It is potentially harmful for the lung and the diaphragm, but its detection is challenging. Magnitude of effort generated by RT is currently unknown. Our objective was to validate supervised methods for automatic detection of RT using only airway pressure (Paw) and flow. A secondary objective was to describe the magnitude of the efforts generated during RT.

Methods

We developed algorithms for detection of RT using Paw and flow waveforms. Experts having Paw, flow and esophageal pressure (Pes) assessed automatic detection accuracy by comparison against visual assessment. Muscular pressure (Pmus) was measured from Pes during RT, triggered breaths and ineffective efforts.

Results

Tracings from 20 hypoxemic patients were used (mean age 65 ± 12 years, 65% male, ICU survival 75%). RT was present in 24% of the breaths ranging from 0 (patients paralyzed or in pressure support ventilation) to 93.3%. Automatic detection accuracy was 95.5%: sensitivity 83.1%, specificity 99.4%, positive predictive value 97.6%, negative predictive value 95.0% and kappa index of 0.87. Pmus of RT ranged from 1.3 to 36.8 cmH20, with a median of 8.7 cmH20. RT with breath stacking had the highest levels of Pmus, and RTs with no breath stacking were of similar magnitude than pressure support breaths.

Conclusion

An automated detection tool using airway pressure and flow can diagnose reverse triggering with excellent accuracy. RT generates a median Pmus of 9 cmH2O with important variability between and within patients.

Trial registration

BEARDS, NCT03447288.
The role of pro-opiomelanocortin in the ACTH–cortisol dissociation of sepsis
Authors: Téblick Arno , Vander Perre Sarah , Pauwels Lies , Derde Sarah , Van Oudenhove Tim , Langouche Lies , Van den Berghe Greet
Published: February 2021

Background

Sepsis is typically hallmarked by high plasma (free) cortisol and suppressed cortisol breakdown, while plasma adrenocorticotropic hormone (ACTH) is not increased, referred to as ‘ACTH–cortisol dissociation.’ We hypothesized that sepsis acutely activates the hypothalamus to generate, via corticotropin-releasing hormone (CRH) and vasopressin (AVP), ACTH-induced hypercortisolemia. Thereafter, via increased availability of free cortisol, of which breakdown is reduced, feedback inhibition at the pituitary level interferes with normal processing of pro-opiomelanocortin (POMC) into ACTH, explaining the ACTH–cortisol dissociation. We further hypothesized that, in this constellation, POMC leaches into the circulation and can contribute to adrenocortical steroidogenesis.

Methods

In two human studies of acute (ICU admission to day 7, N = 71) and prolonged (from ICU day 7 until recovery; N = 65) sepsis-induced critical illness, POMC plasma concentrations were quantified in relation to plasma ACTH and cortisol. In a mouse study of acute (1 day), subacute (3 and 5 days) and prolonged (7 days) fluid-resuscitated, antibiotic-treated sepsis (N = 123), we further documented alterations in hypothalamic CRH and AVP, plasma and pituitary POMC and its glucocorticoid-receptor-regulated processing into ACTH, as well as adrenal cortex integrity and steroidogenesis markers.

Results

The two human studies revealed several-fold elevated plasma concentrations of the ACTH precursor POMC from the acute to the prolonged phase of sepsis and upon recovery (all p < 0.0001), coinciding with the known ACTH–cortisol dissociation. Elevated plasma POMC and ACTH–corticosterone dissociation were confirmed in the mouse model. In mice, sepsis acutely increased hypothalamic mRNA of CRH (p = 0.04) and AVP (p = 0.03) which subsequently normalized. From 3 days onward, pituitary expression of CRH receptor and AVP receptor was increased. From acute throughout prolonged sepsis, pituitary POMC mRNA was always elevated (all p < 0.05). In contrast, markers of POMC processing into ACTH and of ACTH secretion, negatively regulated by glucocorticoid receptor ligand binding, were suppressed at all time points (all p ≤ 0.05). Distorted adrenocortical structure (p < 0.05) and lipid depletion (p < 0.05) were present, while most markers of adrenocortical steroidogenic activity were increased at all time points (all p < 0.05).

Conclusion

Together, these findings suggest that increased circulating POMC, through CRH/AVP-driven POMC expression and impaired processing into ACTH, could represent a new piece in the puzzling ACTH–cortisol dissociation.
Secrecy analysis of short-packet transmissions in ultra-reliable and low-latency communications
Authors: He Jianhua , Zhao Guangheng , Wang Lu , Sun Xue , Yang Lei
Published: February 2021

In this paper, we investigate the secrecy performance of short-packet transmissions in ultra-reliable and low-latency communications (URLLC). We consider the scenario where a multi-antenna source communicates with a single-antenna legitimate receiver requiring ultra-high reliability and low latency, in the presence of a single-antenna eavesdropper. In order to safeguard URLLC, the source transmits the artificial noise (AN) signal together with the confidential signal to confuse the eavesdropper. We adopt a lower bound on the maximal secrecy rate as the secrecy performance metric for short-packet transmissions in URLLC, which takes the target decoding error probabilities at the legitimate receiver and the eavesdropper into account. Using this metric, we first derive a compact expression of the generalized secrecy outage probability (SOP). Then, we formally prove that the generalized SOP is a convex function with respect to the power allocation factor between the confidential signal and the AN signal. We further determine the optimal power allocation factor that minimizes the generalized SOP. The results presented in this work can be useful for designing new secure transmission schemes for URLLC.
A hybrid recommender system based-on link prediction for movie baskets analysis
Authors: Vahidi Farashah Mohammadsadegh , Etebarian Akbar , Azmi Reza , Ebrahimzadeh Dastjerdi Reza
Published: February 2021

Over the past decade, recommendation systems have been one of the most sought after by various researchers. Basket analysis of online systems’ customers and recommending attractive products (movies) to them is very important. Providing an attractive and favorite movie to the customer will increase the sales rate and ultimately improve the system. Various methods have been proposed so far to analyze customer baskets and offer entertaining movies but each of the proposed methods has challenges, such as lack of accuracy and high error of recommendations. In this paper, a link prediction-based method is used to meet the challenges of other methods. The proposed method in this paper consists of four phases: (1) Running the CBRS that in this phase, all users are clustered using Density-based spatial clustering of applications with noise algorithm (DBScan), and classification of new users using Deep Neural Network (DNN) algorithm. (2) Collaborative Recommender System (CRS) Based on Hybrid Similarity Criterion through which similarities are calculated based on a threshold (lambda) between the new user and the users in the selected category. Similarity criteria are determined based on age, gender, and occupation. The collaborative recommender system extracts users who are the most similar to the new user. Then, the higher-rated movie services are suggested to the new user based on the adjacency matrix. (3) Running improved Friendlink algorithm on the dataset to calculate the similarity between users who are connected through the link. (4) This phase is related to the combination of collaborative recommender system’s output and improved Friendlink algorithm. The results show that the Mean Squared Error (MSE) of the proposed model has decreased respectively 8.59%, 8.67%, 8.45% and 8.15% compared to the basic models such as Naive Bayes, multi-attribute decision tree and randomized algorithm. In addition, Mean Absolute Error (MAE) of the proposed method decreased by 4.5% compared to SVD and approximately 4.4% compared to ApproSVD and Root Mean Squared Error (RMSE) of the proposed method decreased by 6.05 % compared to SVD and approximately 6.02 % compared to ApproSVD.
Clinical Characteristics and Histopathological Patterns of Hodgkin Lymphoma and Treatment Outcomes at a Tertiary Cancer Center in Ethiopia
Authors: Adam Makka , Bekueretsion Yonas , Abubeker Abdulaziz , Tadesse Fisihatsion , Kwiecinska Anna , Howe Rawleigh , Petros Beyene , Jerkeman Mats , Gebremedhin Amha
Published: February 2021

PURPOSE

In developing countries, Hodgkin lymphoma (HL) affects the young population. In Ethiopia, nearly 70% of the population are < 35 years of age. Therefore, this study aimed to elucidate the age distribution, histopathologic patterns, clinical characteristics and treatment outcomes of HL in Ethiopia.

MATERIALS AND METHODS

Data from clinical records of 133 consecutive patients with HL between 2014 and 2019 were reviewed and collected. Formalin-fixed paraffin-embedded tissue blocks of HL cases were collected and used for subtype classification.

RESULTS

A total of 68.4% (91) of the patients were male; male-to-female ratio was 2.2:1. The median age was 22 years. The age distribution was 57.1% (76), 30.8% (41), and 2.3% (3) for the age groups (10-29), (30-59), and (60-69) years, respectively. Thirteen percent (12) were associated with HIV. The majority of the cases, 50.4% (67), were of the mixed-cellularity (MCCHL) subtypes and 30% (40) nodular-sclerosis (NSCCHL). Most HIV-associated cases (60%, 6) were of the MCHL subtype. The 4-year overall survival (OS) was 83.1%. The 4-year OS of early-stage patients was 100% and advanced-stage patients with low-risk (International Prognostic Score [IPS] ≤ 2) and high-risk (IPS ≥ 3) were 94.1% and 62.9%, respectively. All patients who received combined-therapy survived, whereas those who received doxorubicin, bleomycin, vinblastine, and dacarbazine only showed a 4-year OS rate of 77.9%.

CONCLUSION

HL affects the youngest and most productive population in Ethiopia. The treatment outcome is favorable in both HIV-associated and non–HIV-associated HL. However, the study population was likely a highly selected group as the majority of the Ethiopian population do not have access to specialized care.
Plasma ctDNA Response Is an Early Marker of Treatment Effect in Advanced NSCLC
Authors: Cheng Michael L. , Lau Christie J. , Milan Marina S. D. , Supplee Julianna G. , Riess Jonathan W. , Bradbury Penelope A. , Jänne Pasi A. , Oxnard Geoffrey R. , Paweletz Cloud P.
Published: February 2021

PURPOSE

Plasma circulating tumor DNA (ctDNA) analysis is routine for genotyping of advanced non–small-cell lung cancer (NSCLC); however, early response assessment using plasma ctDNA has yet to be well characterized.

MATERIALS AND METHODS

Patients with advanced EGFR-mutant NSCLC across three phase I NCI osimertinib combination trials were analyzed in this study, and an institutional cohort of patients with KRAS-, EGFR-, and BRAF-mutant advanced NSCLC receiving systemic treatment was used for validation. Plasma was collected before treatment initiation and serially before each cycle of therapy, and key driver mutations in ctDNA were characterized by droplet digital polymerase chain reaction. Timing of plasma versus imaging response was compared in a separate cohort of patients with EGFR-mutant NSCLC treated with osimertinib. Across cohorts, we also studied ctDNA variability before treatment start.

RESULTS

In the NCI cohort, 14/16 (87.5%) patients exhibited ≥ 90% decrease in mutation abundance by the first on-treatment timepoint (20-28 days from treatment start) with minimal subsequent change. Similarly, 47/56 (83.9%) patients with any decrease in the institutional cohort demonstrated ≥ 90% decrease in mutation abundance by the first follow-up draw (7-30 days from treatment start). All 16 patients in the imaging cohort with radiographic partial response showed best plasma response within one cycle, preceding best radiographic response by a median of 24 weeks (range: 3-147 weeks). Variability in ctDNA levels before treatment start was observed.

CONCLUSION

Plasma ctDNA response is an early phenomenon, with the majority of change detectable within the first cycle of therapy. These kinetics may offer an opportunity for early insight into treatment effect before standard imaging timepoints.
Single-cell sequencing reveals the potential oncogenic expression atlas of human iPSC-derived cardiomyocytes
Authors: Ou Minglin , Zhao Min , Li Chunhong , Tang Donge , Xu Yong , Dai Weier , Sui Weiguo , Zhang Yue , Xiang Zhen , Mo Chune , Lin Hua , Dai Yong
Published: February 2021

Human induced pluripotent stem cells (iPSCs) are important source for regenerative medicine. However, the links between pluripotency and oncogenic transformation raise safety issues. To understand the characteristics of iPSC-derived cells at single-cell resolution, we directly reprogrammed two human iPSC lines into cardiomyocytes and collected cells from four time points during cardiac differentiation for single-cell sequencing. We captured 32,365 cells and identified five molecularly distinct clusters that aligned well with our reconstructed differentiation trajectory. We discovered a set of dynamic expression events related to the upregulation of oncogenes and the decreasing expression of tumor suppressor genes during cardiac differentiation, which were similar to the gain-of-function and loss-of-function patterns during oncogenesis. In practice, we characterized the dynamic expression of the TP53 and Yamanaka factor genes (OCT4, SOX2, KLF4 and MYC), which were widely used for human iPSCs lines generation; and revealed the co-occurrence of MYC overexpression and TP53 silencing in some of human iPSC-derived TNNT2+ cardiomyocytes. In summary, our oncogenic expression atlas is valuable for human iPSCs application and the single-cell resolution highlights the clues potentially associated with the carcinogenic risk of human iPSC-derived cells.
ERECTA family signaling constrains CLAVATA3 and WUSCHEL to the center of the shoot apical meristem
Authors: Zhang Liang , DeGennaro Daniel , Lin Guangzhong , Chai Jijie , Shpak Elena D.
Published: February 2021

The shoot apical meristem (SAM) is a reservoir of stem cells that gives rise to all post-embryonic above-ground plant organs. The size of the SAM remains stable over time owing to a precise balance of stem cell replenishment versus cell incorporation into organ primordia. The WUSCHEL (WUS)/CLAVATA (CLV) negative feedback loop is central to SAM size regulation. Its correct function depends on accurate spatial expression of WUS and CLV3. A signaling pathway, consisting of ERECTA family (ERf) receptors and EPIDERMAL PATTERNING FACTOR LIKE (EPFL) ligands, restricts SAM width and promotes leaf initiation. Although ERf receptors are expressed throughout the SAM, EPFL ligands are expressed in its periphery. Our genetic analysis of Arabidopsis demonstrated that ERfs and CLV3 synergistically regulate the size of the SAM, and wus is epistatic to ERf genes. Furthermore, activation of ERf signaling with exogenous EPFLs resulted in a rapid decrease of CLV3 and WUS expression. ERf-EPFL signaling inhibits expression of WUS and CLV3 in the periphery of the SAM, confining them to the center. These findings establish the molecular mechanism for stem cell positioning along the radial axis.
PRDM16 regulates a temporal transcriptional program to promote progression of cortical neural progenitors
Authors: He Li , Jones Jennifer , He Weiguo , Bjork Bryan C. , Wen Jiayu , Dai Qi
Published: February 2021

Radial glia (RG) in the neocortex sequentially generate distinct subtypes of projection neurons, accounting for the diversity and complex assembly of cortical neural circuits. Mechanisms that drive the rapid and precise temporal progression of RG are beginning to be elucidated. Here, we reveal that the RG-specific transcriptional regulator PRDM16 promotes the transition of early to late phase of neurogenesis in the mouse neocortex. Loss of Prdm16 delays the timely progression of RG, leading to defective cortical laminar organization. Our genomic analyses demonstrate that PRDM16 regulates a subset of genes that are dynamically expressed between early and late neurogenesis. We show that PRDM16 suppresses target gene expression through limiting chromatin accessibility of permissive enhancers. We further confirm that crucial target genes regulated by PRDM16 are neuronal specification genes, cell cycle regulators and molecules required for neuronal migration. These findings provide evidence to support the finding that neural progenitors temporally shift the gene expression program to achieve neural cell diversity.
Retrospective comparative study of efficacy, safety and outcome of percutaneous intervention for Budd-Chiari syndrome patients with bilirubin less than 3 and 3–6 mg/dl
Authors: Patidar Yashwant , Pal Chandan Kumar , Mukund Amar , Kumar Guresh , Sarin Shiv Kumar
Published: February 2021

Objective:

Comparing the efficacy, safety and outcome of percutaneous intrervention for Budd-Chiari Syndrome (BCS) patients with bilirubin less than 3 and 3–6 mg dl−1.

Methods and materials:

188 BCS patients having serum bilirubin ≤6 mg dl−1 and underwent percutaneous interventions were divided into two groups based on bilirubin level: 151 patients having bilirubin <3 mg dl−1 were included in Group 1; and 37 patients having bilirubin 3–6 mg dl−1 were included in Group 2. Both group were compare for technical success (successful recanalization of hepatic venous stenosis or creation of portocaval shunt with post-procedure gradient ≤5 mm of Hg), Safety (procedure-related mortality/morbidity or patient required transplantation) and outcome (resolution of clinical symptoms and survival).

Results:

Technical success was 94.7% in Group 1–89.1% in Group 2 with overall success rate was 93.6%. No significant differences observed between the two groups in regards to procedure related complication. Overall transplant-free survival at 1 and 5 years after intervention in both groups was 96.3 and 91.2% respectively. 1-year and 5-year survivals in Group 1 was 96.7%, and 93.1%, whereas Group 2 was 94.6 and 90.1% with no statically significantly difference between the two groups (p = 0.59). Percutaneous intervention results are good in patients having bilirubin up to 6 mg dl−1, i.e. mild to moderate liver dysfunctions.

Conclusion:

Technical success, survival and outcome of percutaneous intervention in BCS patients having serum bilirubin 3–6 mg dl−1 was comparable to patients having bilirubin level <3 mg dl−1.

Advances in knowledge:

Percutaneous intervention treatment is suitable for treatment for symptomatic BCS patients having bilirubin up to 6 mg  dl−1.
MRI-defined high-risk rectal cancer patients: outcome comparison between neoadjuvant chemoradiotherapy plus TME and TME plus adjuvant chemotherapy or TME alone
Authors: Jia Xiaoxuan , Xie Peiyi , Bi Liang , Meng Xiaochun , Wang Ziqiang , Hong Nan , Wang Yi
Published: February 2021

Objective:

The goal of this study was to investigate whether neoadjuvant chemoradiotherapy (NCRT) plus total mesorectal excision (TME) would improve the outcome of patients with MRI-defined high-risk rectal cancer compared with TME plus adjuvant chemotherapy (ACT) or TME alone.

Methods:

We retrospectively enrolled 362 patients with MRI-defined high-risk rectal cancer who were treated with NCRT plus TME, TME plus ACT, or TME alone between January 2008 and August 2018. Cases with a high-risk tumor stage, positive extramural venous invasion, or mesorectal fascia involvement on baseline MRI were considered cases of high-risk rectal cancer. We matched patients treated with NCRT plus TME to patients treated with TME plus ACT and to those treated with TME alone. Kaplan–Meier curves were used to compare local recurrence (LR), disease-free survival (DFS), and overall survival (OS) rates.

Results:

The cumulative 3 year LR rate in the matched NCRT plus TME group was more favorable than in the TME plus ACT group (0% vs 5.1%; p = 0.037; n = 98) and in the TME alone group (0% vs 11.5%; p = 0.016; n = 61). Patients who received NCRT plus TME demonstrated better cumulative 3 year DFS rates than patients treated with TME plus ACT (85.7% vs 65.3%; p = 0.009) or with TME alone (86.9% vs 68.9%; p = 0.046). No difference in OS was observed among the groups.

Conclusion:

NCRT may improve DFS and LR rates in patients with MRI-defined high-risk rectal cancer when compared with TME plus ACT or TME alone.

Advances in knowledge:

This study illustrated the specific benefit of NCRT on the outcome measures of MRI-defined high-risk rectal cancer compared with TME plus ACT or TME alone, which was not clearly clarified in previous studies enrolling all patients with Stage II/III rectal cancer.
Self-care management, knowledge, self-efficacy for medication and Quality of Life in chronic heart failure patients
Authors: Kroustalli Elpida , Papadopoulos Constantinos H , Vasileiadis Ioannis , Kalokairinou Athena , Kiokas Sotirios , Karatzanos Eleftherios , Nanas Serafeim
Published: February 2021

Background: The management of Heart Failure (HF) is the cornerstone for the appropriate therapy and the knowledge obtained concerning the disease is known to affect self-care behaviours. Aim: The aim was to test the association between self-care management, knowledge, self-efficacy for medication and quality of life in chronic HF patients.Material and Method: A cross-sectional study was conducted and four questionnaires were used: Atlanta Heart Failure Knowledge Test (AHFK), Minnesota Living with Heart Failure (HMLHFQ), Self-Efficacy for Appropriate Medication Use Scale (SEAMS), European Heart Failure Self-care Behaviour Scale (EHFScBS-9). Multiple linear regression analysis was performed to identify independently associated variables with study subscales.Results: The sample consisted of 122 Heart Failure patients (102 men-20 women) with mean age 67.1 years (SD=12.3). Scores on Fluid and sodium management, Physical activity and recognition of deteriorating symptoms were  significantly greater  as compared with scores on Adhering to recommendations (p<0.001), indicating that the needs concerning Adhering to recommendations were greater.  Linear regression analyses showed that score on knowledge-test and New York Heart Association (NYHA) class were predictive of medication adherence factors. Better knowledge was associated with better medication adherence, while worse scores were found in subjects with NYHA class III or IV as compared to those with NYHA class I or II. Additionally, Knowledge and years of Education were associated with Self-care behaviour factors (β=0.44, SE=0.08, p<0.001). Conclusions: Patients at a higher level of HF knowledge show better adherence to the Medication. Self-care behavior and life quality are improved.
What contextual factors and mechanisms facilitate male involvement in women's sexual and reproductive health in Sub-Saharan Africa? A rapid realist review protocol
Authors: Mwendwa Purity , Karani Caroline , Kamolo Elizabeth , Kroll Thilo , De Brún Aoife , McAuliffe Eilish
Published: February 2021

Background:  Sexual and reproductive health (SRH) outcomes of women within low resource contexts continue to be of concern to policymakers. Notably, sub-Saharan Africa (SSA) continues to lag behind other regions of the world in improving SRH outcomes for women in the region. A key suggested strategy is male involvement through interventions that respect, promote and facilitate women in taking care of themselves and their new-borns. However, factors such as social-cultural barriers may preclude men's involvement in these programmes. There is a need for a context-specific understanding of gender dynamics and interaction and the mechanisms that enhance or impede men's involvement.

Methods: We will employ a rapid realist review (RRR) methodology to examine what mechanisms and contextual factors are essential to facilitate the involvement of men in women's SRH programmes in SSA. In keeping with the realist literature we will follow six steps, which will include: (1) developing a theory, (2) developing a search strategy, (3) selecting and appraising documents, (4) extracting data, (5) analysing data and synthesising the evidence, and (6) presenting and disseminating a revised theory. We will also engage with key stakeholders who will provide local contextual insights and with experts in the subject area. The review findings will be shared with relevant stakeholders using a variety of avenues including through publications, at conferences and on social media platforms.

Discussion: This review will identify the mechanisms and contextual factors that facilitate or hinder men's involvement in women's SRH programmes in SSA. The rationale for adopting an RRR approach is to help gather the information within a relatively short period to ensure relevance of findings to policymakers in SSA. Results from this work also have the potential to be adapted to the other contexts, for example, Ireland and the UK, which have a growing population of people from SSA.