bluuebunny/crossref_metadata_2025_split huggingface dataset:
High recombination rate of hepatitis C virus revealed by a green fluorescent protein reconstitution cell system
Authors: Galli Andrea , Fahnøe Ulrik , Bukh Jens 
Published: December 2021

AbstractGenetic recombination is an important evolutionary mechanism for RNA viruses and can facilitate escape from immune and drug pressure. Recombinant hepatitis C virus (HCV) variants have rarely been detected in patients, suggesting that HCV has intrinsic low recombination rate. Recombination of HCV has been demonstrated in vitro between non-functional genomes, but its frequency and relevance for viral evolution and life cycle has not been clarified. We developed a cell-based assay to detect and quantify recombination between fully viable HCV genomes, using the reconstitution of green fluorescent protein (GFP) as a surrogate marker for recombination. Here, two GFP-expressing HCV genomes carrying different inactivating GFP mutations can produce a virus carrying a functional GFP by recombining within the GFP region. Generated constructs allowed quantification of recombination rates between markers spaced 603 and 553 nucleotides apart by flow cytometry and next-generation sequencing (NGS). Viral constructs showed comparable spread kinetics and reached similar infectivity titers in Huh7.5 cells, allowing their use in co-transfections and co-infections. Single-cycle co-transfection experiments, performed in CD81-deficient S29 cells, showed GFP expression in double-infected cells, demonstrating genome mixing and occurrence of recombination. Quantification of recombinant genomes by NGS revealed an average rate of 6.1 per cent, corresponding to 49 per cent of maximum detectable recombination (MDR). Experiments examining recombination during the full replication cycle of HCV, performed in Huh7.5 cells, demonstrated average recombination rates of 5.0 per cent (40.0 per cent MDR) and 3.6 per cent (28.8 per cent MDR) for markers spaced by 603 and 553 nucleotides, respectively, supporting a linear relationship between marker distance and recombination rates. First passage infections using recombinant virus supernatant resulted in comparable recombination rates of 5.9 per cent (47.2 per cent MDR) and 3.5 per cent (28.0 per cent MDR), respectively, for markers spaced by 603 and 553 nucleotides. We developed a functional cell-based assay that, to the best of our knowledge, allows for the first time detailed quantification of recombination rates using fully viable HCV constructs. Our data indicate that HCV recombines at high frequency between highly similar genomes and that the frequency of recombination increases with the distance between marker sites. These results have implication for our understanding of HCV evolution and emphasize the importance of recombination in the reassortment of mutations in the HCV genome.
Lymphadenopathy secondary to tattoo ink in a patient with a history of Hodgkin lymphoma
Authors: Melnick Natalie , Pierce Bradley 
Published: December 2021

ABSTRACT
The finding of lymphadenopathy on physical examination and radiographically can suggest a wide range of differential diagnoses for patients, including a benign inflammatory process, infection, or malignancy. This article describes a patient with a history of Hodgkin lymphoma who developed postremission left axillary lymphadenopathy caused by deposits of tattoo ink in the node.
Clinical considerations for the evaluation of patients with left ventricular assist devices
Authors: McMullen Leah , Barker Kelly , Fried Justin , Wagener Gebhard 
Published: December 2021

ABSTRACT
A left ventricular assist device (LVAD) provides mechanical circulatory support for patients with end-stage heart failure. As these devices become more prevalent, clinicians must be familiar with the device's function, common complications, and management strategies when evaluating this patient population.
Comparison of the mean of the first two blood pressure readings with the overall mean of three readings on a single occasion
Authors: Xu Shao-Kun , Chen Xin , Sheng Chang-Sheng , Cheng Yi-Bang , Wang Hong-Yu , Yu Wei , Li Yan , Wang Ji-Guang 
Published: December 2021

Objective:
Guidelines differed on the required number of blood pressure (BP) readings for accurate BP assessment. We, therefore, compared the mean of the first two BP readings with the overall mean of three readings in the diagnosis of hypertension.

Methods:
BP was measured three times consecutively with a 1 min interval using a validated automated electronic BP monitor in volunteers aged at least 18 years. The mean of the first and second BP readings was compared with the mean of the three blood pressure readings for the diagnostic accuracy of hypertension.

Results:
Of the 77 520 study participants, 65.2 and 25.2% had a SBP or DBP difference at least 5 mmHg and at least 10 mmHg between the first and second BP readings, respectively. Regardless whether the BP difference between the first two BP readings was at least 5 mmHg or at least 10 mmHg for systolic and diastolic alone or both, significant (P < 0.0001) SBP/DBP differences between the mean of the first two BP readings and the overall mean of three readings were observed with an absolute value up to 1.28/1.11 mmHg. However, the mean of the first two BP readings exhibited good reliability and sufficient agreement in the diagnosis of hypertension with a kappa statistic at least 0.88, except that the difference between the first and second BP readings was at least 10 mmHg for both systolic and diastolic (κ=0.79). The diagnostic accuracy was similar across age quartile, sex, and BP category.

Conclusion:
Two BP readings may be sufficient, unless the BP difference between the two readings was at least 10 mmHg for both systolic and diastolic.
The association of uric acid with mortality modifies at old age: data from the uric acid right for heart health (URRAH) study
Authors: Ungar Andrea , Rivasi Giulia , Di Bari Mauro , Virdis Agostino , Casiglia Edoardo , Masi Stefano , Mengozzi Alessandro , Barbagallo Carlo M. , Bombelli Michele , Bruno Bernardino , Cicero Arrigo F.G. , Cirillo Massimo , Cirillo Pietro , Desideri Giovambattista , D’elia Lanfranco , Ferri Claudio , Galletti Ferruccio , Gesualdo Loreto , Giannattasio Cristina , Iaccarino Guido , Ciccarelli Michele , Lippa Luciano , Mallamaci Francesca , Maloberti Alessandro , Mazza Alberto , Muiesan Maria Lorenza , Nazzaro Pietro , Palatini Paolo , Parati Gianfranco , Pontremoli Roberto , Quarti-Trevano Fosca , Rattazzi Marcello , Salvetti Massimo , Tikhonoff Valérie , Tocci Giuliano , Cianci Rosario , Verdecchia Paolo , Viazzi Francesca , Volpe Massimo , Grassi Guido , Borghi Claudio 
Published: December 2021

Objectives:
In older individuals, the role of serum uric acid (SUA) as risk factor for mortality is debated. This study investigated the association of SUA with all-cause and cardiovascular (CV) mortality in older adults participating in the large multicentre observational uric acid right for heart health (URRAH) study.

Methods:
Eight thousand URRAH participants aged 65+ were included in the analysis. The predictive role of SUA was assessed using Cox regression models stratified according to the cut-off age of 75. SUA was tested as continuous and categorical variable (age-specific quartiles). The prognostic threshold of SUA for mortality was analysed using receiver operating characteristic curves.

Results:
Among participants aged 65–74, multivariate Cox regression analysis adjusted for CV risk factors and comorbidities identified an independent association of SUA with both all-cause mortality (hazard ratio [HR] 1.169, 95% confidence interval [CI] 1.107–1.235) and CV mortality (HR 1.146, 95% CI 1.064–1.235). The cut-off value of 4.8 mg/dl discriminated mortality status. In participants aged 75+, we observed a J-shaped relationship of SUA with all-cause and CV mortality, with risk increasing at extreme SUA levels.

Conclusions:
These results confirmed the predictive role of SUA for all-cause and CV mortality in older adults, while revealing considerable age-related differences. Mortality risk increased at higher SUA levels in participants aged 65–74, with a prognostic threshold of 4.8 mg/dl. The relationship between SUA and mortality was J-shaped in oldest participants. Large interventional studies are needed to clarify the benefits and possible risks of urate-lowering treatments in older adults.
HMB and leucine supplementation during critical illness and recovery
Authors: Bear Danielle E. , Rooyackers Olav 
Published: December 2021

Purpose of review
Skeletal muscle wasting is a serious consequence of critical illness, which may impact on long term physical and functional disability. To date, no intervention has been proven to reduce skeletal muscle wasting. Leucine and it's metabolite β-hydroxy-β-methylbutyrate (HMB) have been proposed as interventions. This review details the mechanism of action of both leucine and HMB, discusses the most recent research for both leucine and HMB and lastly discusses considerations for future research.

Recent findings
Only one study of leucine in critical illness has recently been published. This was a feasibility study where the physiological and muscle related outcomes were not reported to be feasible. Three studies on HMB have been reported recently with no effect seen on either muscle mass or strength. The main limitation in our understanding of the potential use of leucine or HMB on skeletal muscle wasting is the lack of mechanistic studies available in this population.

Summary
Mechanistic studies should be a priority before embarking on further randomized controlled trials related to this topic.
Case report of pure single-port robotic left lateral sectionectomy using the da Vinci SP system
Authors: Kim Wan-Joon , Park Pyoung-Jae , Choi Sae-Byeol , Kim Wan-Bae 
Published: December 2021

Abstract

Introduction:
Since its first appearance in the early 1990s, laparoscopic hepatic resection has become increasingly accepted and recognized as safe as laparotomy. The recent introduction of robotic surgery systems has brought new innovations to the field of minimally invasive surgery, such as laparoscopic surgery. The da Vinci line of surgical systems has recently released a true single-port platform called the da Vinci SP system, which has 3 fully wristed and elbowed instruments and a flexible camera in a single 2.5 cm cannula. We present the first case of robotic liver resection using the da Vinci SP system and demonstrate the technical feasibility of this platform.

Patient concerns and diagnosis:
A 63-year-old woman presented with elevated liver function test results and abdominal pain. Computed tomography (CT) and magnetic resonance cholangiopancreatography showed multiple intrahepatic duct stones in the left lateral section and distal common bile duct stones near the ampulla of Vater.

Interventions:
The docking time was 8 minute. The patient underwent successful da Vinci SP with a total operation time of 135 minute. The estimated blood loss was 50.0 ml. No significant intraoperative events were observed.

Outcomes:
The numerical pain intensity score was 3/10 in the immediate postoperative period and 1/10 on postoperative day 2. The patient was discharged on postoperative day 5 after verifying that the CT scan did not show any surgical complications.

Conclusion:
We report a technique of left lateral sectionectomy, without the use of an additional port, via the da Vinci SP system. The present case suggests that minor hepatic resection is technically feasible and safe with the new da Vinci SP system in select patients. For the active application of the da Vinci SP system in hepatobiliary surgery, further device development and research are needed.
Pre-operative angle of trunk rotation in prone position estimates postoperative correction results
Authors: Uehara Masashi , Ikegami Shota , Kuraishi Shugo , Oba Hiroki , Takizawa Takashi , Munakata Ryo , Hatakenaka Terue , Koseki Michihiko , Takahashi Jun 
Published: December 2021

Abstract
This study investigated whether postoperative rotational deformity in adolescent idiopathic scoliosis patients could be predicted by prone-position pre-operative angle of trunk rotation (ATR).
Surgical rib hump correction is performed with the patient in a prone position. However, the association between pre-operative ATR in the prone position and postoperative ATR results is unknown.
Thirty-four consecutive patients who underwent skip pedicle screw fixation for Lenke type 1 or 2 adolescent idiopathic scoliosis were retrospectively reviewed. All subjects were followed for a minimum of 1 year. ATR measurements were taken for the standing-flexion position with a scoliometer before surgery and at 1 year afterward. Pre-operative measurements were also taken for the prone position. Correlations between pre- and postoperative ATR were calculated by means of Pearson correlation coefficient. Associations between the correction angle from the standing-flexion position to prone position and postoperative standing-flexion correction angle were determined by linear regression analysis.
Pre- and postoperative ATR for the standing-flexion position showed a moderate association (r = 0.64, P < .01). A similar correlation was seen for pre-operative prone-position ATR and postoperative standing-flexion ATR (r = 0.56, P < .01). In linear regression analysis, there was significant proportional error between the correction angle from the standing-flexion position to prone position and postoperative standing-flexion correction angle (β = 0.40, P < .01).
In conclusion, pre-operative ATR in either standing-flexion or prone position and postoperative standing-flexion ATR displayed moderate associations. Linear regression analysis revealed that ATR correction angle could be estimated by calculating the correction gains of 0.4° per 1° of correction angle in the prone position.
Triaging urological surgeries to cope with the coronavirus-19 pandemic
Authors: Spooner Jesse , Lawen Tarek , Ory Jesse 
Published: December 2021

Purpose of review
The coronavirus-19 (COVID-19) pandemic has led to strains on hospital resources and difficulties in safely and effectively triaging surgical procedures. In this article, we discuss the important considerations for triaging urologic surgeries during a global pandemic, mitigating factors on how to perform surgeries safely, and general guidelines for specific surgeries.

Recent findings
Many urological procedures have been cut back due to the pandemic, with benign disease states being most affected whereas oncology cases affected least. Current recommendations in urology triage life-threatening conditions, or conditions that may lead to life-threatening ailments as a priority for treatment during the pandemic. Additionally, published recommendations have been put forth recommending all surgical patients be screened for COVID-19 to protect staff, prevent disease dissemination, and to educate patients on worse outcomes that can occur if infected with COVID-19 in the postoperative period.

Summary
COVID-19 has caused worldwide shortages of healthcare resources and increased the need to ethically triage resources to adequately treat the urologic community. These resource limitations have led to increased wait times and cancellations of many urology surgeries that are considered ’elective’.
Medicolegal Implications of Fatalities Because of Entanglement in the Augers of Feed Mixer Wagons
Authors: Moreschi Carlo , Da Broi Ugo , Tse Rexson , Garland Jack , Ondruschka Benjamin , Cividino Sirio Rossano , Vello Michela , Gubiani Rino 
Published: December 2021

Abstract
Feed mixer or total mixed ration mixer wagons are powerful agricultural machines used to shred and mix silage with other ingredients and deliver it direct to the feeding troughs on livestock farms. Fatalities involving these feed mixers may occur when operators become trapped in the augers or, less frequently, are crushed by moving wagons. Death can occur very rapidly because of dismemberment, multiple lesions, or crushing. The aim of this review is to focus on the diagnostic evaluations that need to be performed to confirm that the death was accidental and to exclude a hypothesis of murder or suicide. Forensic investigations in such cases must involve the detailed analysis of the death scene and the mechanical characteristics of the machinery with an accurate postmortem and toxicological examination.
Drowning Accidents in a Spanish Pediatric Intensive Care Unit
Authors: Salas Ballestín Alberto , Frontera Juan Guillem , Sharluyan Petrosyan Artur , Chocano González Eva , Figuerola Mulet Joan , De Carlos Vicente Juan Carlos 
Published: December 2021

Introduction
Drowning is one of the most frequent accidents in children. We aimed to describe demographic and epidemiological characteristics of drowned children who required admission to a pediatric intensive care unit (PICU) to identify risk factors to guide possible preventive measures to avoid severe drowning.

Methods
We conducted an observational study for 29 years (retrospective between 1991 and 2004; prospective between 2005 and 2019) that included all children (0–15 years old) requiring PICU admission after drowning. Data regarding patient characteristics, accident circumstances, and neurological outcomes at PICU discharge were analyzed.

Results
A total of 160 patients were included, with no significant decrease over the study period. There was a predominance of males (75%), young age (60%; 1–5 years), summer months (91.1%; May–September), tourists (14.12 [95% confidence interval, 9.2–21.7] times higher risk of drowning than residents), swimming pool accidents (88.8%), and inadequate supervision (77.9%). The mortality was 18.7%, and 7.5% of admitted children had severe neurological sequelae. The initial resuscitation maneuvers by accident witnesses were incorrect in nearly half of the patients in whom these could be analyzed.

Conclusions
Emphasis should be placed on implementing preventive measures, focused on the described risk groups, and insisting on adequate supervision, swimming training programs, and training of the general population in safe rescue and cardiopulmonary resuscitation.
Blockade of TMPRSS2-mediated priming of SARS-CoV-2 by the N-terminal peptide of lactoferrin
Authors: Ohradanova-Repic Anna , Gebetsberger Laura , Tajti Gabor , Ondrovičová Gabriela , Praženicová Romana , Skrabana Rostislav , Baráth Peter , Stockinger Hannes , Leksa Vladimir 
Published: December 2021

AbstractIn addition to vaccines, there is an urgent need for supplemental antiviral therapeutics to dampen the persistent COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2). The transmembrane protease serine 2 (TMPRSS2), which is responsible for the proteolytic processing of the SARS-CoV-2 spike protein as virus priming for cell entry, appears as a rational therapeutic target for the clearance of SARS-CoV-2 infection. Accordingly, selective inhibitors of TMPRSS2 represent potential tools for prevention and treatment of COVID-19. Here, we tested the inhibitory capacities of the human milk glycoprotein lactoferrin and its N-terminal peptide pLF1, which we identified as inhibitors of plasminogen, a serine protease homologous to TMPRSS2. In vitro proteolysis assays revealed that, unlike full-length lactoferrin, pLF1 significantly inhibited the proteolytic activity of TMPRSS2. pLF1 inhibited both the proteolytic processing of the SARS-CoV-2 spike protein and the SARS-CoV-2 infection of simian Vero cells. Because lactoferrin is a natural product and several biologically active peptides, such as the N-terminally derived lactoferricins, are produced naturally by pepsin-mediated digestion, natural or synthetic peptides from lactoferrin represent well-achievable candidates for supporting prevention and treatment of COVID-19.
Sustained TNF signaling is required for the synaptic and behavioral response to acute stress
Authors: Kemp Gina M , Altimimi Haider F , Nho Yoonmi , Heir Renu , Stellwagen David 
Published: December 2021

AbstractAcute stress triggers plasticity of forebrain synapses as well as behavioral changes. Here we reveal that Tumor Necrosis Factor α (TNF) is a required downstream mediator of the stress response in mice, necessary for stress-induced synaptic potentiation in the ventral hippocampus and for an increase in anxiety-like behaviour. Acute stress is sufficient to activate microglia, triggering the long-term release TNF. Critically, on-going TNF signaling in the ventral hippocampus is necessary to sustain both the stress-induced synaptic and behavioral changes, as these could be reversed hours after induction by antagonizing TNF signaling. This demonstrates that TNF maintains the synaptic and behavioral stress responsein vivo, making TNF a potential novel therapeutic target for stress disorders.
Lrig1 and Wnt dependent niches dictate segregation of resident immune cells and melanocytes in murine tail epidermis
Authors: Baess Susanne C. , Burkhart Ann-Kathrin , Cappello Sabrina , Graband Annika , Seré Kristin , Zenke Martin , Niemann Catherin , Iden Sandra 
Published: December 2021

ABSTRACTThe barrier-forming, self-renewing mammalian epidermis comprises keratinocytes, pigment- producing melanocytes, and resident immune cells as first-line host defense. In murine tail skin, interfollicular epidermis patterns into pigmented ′scale′ and hypopigmented ′interscale′ epidermis. Why and how mature melanocytes accumulate in scale epidermis is unresolved. Here, we delineate a cellular hierarchy among epidermal cell types that determines skin patterning. Already during postnatal development, melanocytes co-segregate with newly forming scale compartments. Intriguingly, this process coincides with partitioning of both Langerhans cells and dendritic epidermal T-cells to interscale epidermis, suggesting functional segregation of pigmentation and immune surveillance. Analysis of non-pigmented mice and of mice lacking melanocytes or resident immune cells revealed that immunocyte patterning is melanocyte- and melanin-independent, and,vice versa, immune cells do not control melanocyte localization. Instead, genetically enforced progressive scale fusion uponLrig1deletion showed that melanocytes and immune cells dynamically follow epithelial scale:interscale patterns. Importantly, disrupting Wnt-Lef1 function in keratinocytes caused melanocyte mislocalization to interscale epidermis, implicating canonical Wnt signaling in organizing the pigmentation pattern. Together, this work uncovered cellular and molecular principles underlying the compartmentalization of tissue functions in skin.SUMMARY STATEMENTPigmentation and immune surveillance functions in murine tail skin are spatially segregated by Lrig1- and Wnt-Lef1-dependent keratinocyte lineages that control the partitioning of melanocytes and tissue-resident immune cells into distinct epidermal niches.
Myopathy mutations in DNAJB6 slow conformer specific substrate processing that is corrected by NEF modulation
Authors: Bhadra Ankan K. , Rau Michael J. , Daw Jil A. , Fitzpatrick James A.J. , Weihl Conrad C. , True Heather L. 
Published: December 2021

AbstractMolecular chaperones, or heat shock proteins (HSPs), protect against the toxic misfolding and aggregation of proteins. As such, mutations or deficiencies within the chaperone network can lead to disease. In fact, dominant mutations in DNAJB6 (Hsp40/Sis1), an Hsp70 co-chaperone, leads to a protein aggregate myopathy termed Limb-Girdle Muscular Dystrophy Type D1 (LGMDD1). DNAJB6 client proteins and co-chaperone interactions in skeletal muscle are not known. Here, we used the yeast prion model client in conjunction with in vitro chaperone activity assays to gain mechanistic insights, and found that LGMDD1 mutants affect Hsp40 functions. Strikingly, the mutants changed the structure of client protein aggregates, as determined by altered distribution of prion strains. They also impair the Hsp70 ATPase cycle, dimerization, and substrate processing and consequently poison the function of wild-type protein. These results define the mechanisms by which LGMDD1 mutations alter chaperone activity and provide avenues for therapeutic intervention.