bluuebunny/crossref_metadata_2025_split huggingface dataset:
Small-Molecule Natural Product Physachenolide C Potentiates Immunotherapy Efficacy by Targeting BET Proteins
Authors: Tewary Poonam , Brooks Alan D. , Xu Ya-Ming , Wijeratne E.M. Kithsiri , Babyak Ashley L. , Back Timothy C. , Chari Raj , Evans Christine N. , Henrich Curtis J. , Meyer Thomas J. , Edmondson Elijah F. , de Aquino Maria T. Prudente , Kanagasabai Thanigaivelan , Shanker Anil , Gunatilaka A.A. Leslie , Sayers Thomas J. 
Published: April 2021

AbstractScreening for sensitizers of cancer cells to TRAIL-mediated apoptosis identified a natural product of the 17β-hydroxywithanolide (17-BHW) class, physachenolide C (PCC), as a promising hit. In this study, we show that PCC was also able to sensitize melanoma and renal carcinoma cells to apoptosis in response not only to TRAIL, but also to the synthetic polynucleotide poly I:C, a viral mimetic and immune activator, by reducing levels of antiapoptotic proteins cFLIP and Livin. Both death receptor and TLR3 signaling elicited subsequent increased assembly of a proapoptotic ripoptosome signaling complex. Administration of a combination of PCC and poly I:C in human M14 melanoma xenograft and a syngeneic B16 melanoma model provided significant therapeutic benefit as compared with individual agents. In addition, PCC enhanced melanoma cell death in response to activated human T cells in vitro and in vivo in a death ligand–dependent manner. Biochemical mechanism-of-action studies established bromo and extraterminal domain (BET) proteins as major cellular targets of PCC. Thus, by targeting of BET proteins to reduce antiapoptotic proteins and enhance caspase-8–dependent apoptosis of cancer cells, PCC represents a unique agent that can potentially be used in combination with various immunotherapeutic approaches to promote tumor regression and improve outcome.Significance:These findings demonstrate that PCC selectively sensitizes cancer cells to immune-mediated cell death, potentially improving the efficacy of cancer immunotherapies.
Sex and Racial Differences in Autopsy-Defined Causes of Presumed Sudden Cardiac Death
Authors: Tseng Zian H. , Ramakrishna Satvik , Salazar James W. , Vittinghoff Eric , Olgin Jeffrey E. , Moffatt Ellen 
Published: April 2021

Background:
Sudden cardiac death (SCD) studies report higher incidence in men and Black people but presume cardiac cause. We sought to identify sex and racial differences in rates and causes of presumed SCDs in a prospective postmortem study in San Francisco County.

Methods:
All incident presumed SCDs meeting the World Health Organization definition ages 18 to 90 were autopsied via active surveillance of consecutive out-of-hospital deaths in the POST SCD study (Postmortem Systematic Investigation of Sudden Cardiac Death; February 1, 2011, to March 1, 2014). Autopsy-defined sudden arrhythmic deaths had no extracardiac cause or acute heart failure.

Results:

Among 541 presumed SCDs, 525 (97%) were autopsied; 362 (69%) were men, 110 Asian (21%), 81 Black (15%), 40 Hispanic (8%), 279 White (53%), and 15 other race (3%). Adjusted for age and race, women had more noncardiac causes of presumed SCD, including pulmonary emboli (8% versus 2%) and neurological causes (10% versus 3%, both
P
<0.01). Of autopsy-defined sudden arrhythmic death, men had 3-fold higher rates while women had more primary electrical disease (4% versus 2%;
P
=0.02) and nonischemic causes (53% versus 39%;
P
<0.01). Age-adjusted incidence rate ratios were higher for Black women (2.55;
P
<0.01) and lower for Asian and Hispanic men (0.51 for both;
P
<0.05) than their White counterparts. Myocardial infarction with nonobstructive coronary arteries was more common among sudden arrhythmic deaths in Asians than Whites (7% versus 1%; adjusted
P
<0.05). Sudden neurological deaths were more common in Asians, endocrine causes more common in Blacks, and gastrointestinal causes more common in Hispanics than in Whites (adjusted
P
, all <0.05).

Conclusions:
In this countywide postmortem study of presumed SCDs, women had more nonischemic and noncardiac causes. Black women had higher rates of autopsy-defined sudden arrhythmic death than White women while Asian and Hispanic men had lower rates than White men. These findings have implications for risk stratification and prevention of sudden mortality in women and minority populations.
Radiofrequency Versus Cryoballoon Catheter Ablation for Paroxysmal Atrial Fibrillation: Durability of Pulmonary Vein Isolation and Effect on Atrial Fibrillation Burden: The RACE-AF Randomized Controlled Trial
Authors: Sørensen Samuel K. , Johannessen Arne , Worck René , Hansen Morten L. , Hansen Jim 
Published: April 2021

Background:
Recurrent paroxysmal atrial fibrillation (AF) after catheter ablation is presumably caused by failure to achieve durable pulmonary vein isolation (PVI). The primary methods of PVI are radiofrequency catheter ablation (RF) and cryoballoon catheter ablation (CRYO), but these methods have not been directly compared with respect to PVI durability and the effect thereof on AF burden (% of time in AF).

Methods:
Accordingly, we performed a randomized trial including 98 patients (68% male, 61 [55–67] years) with paroxysmal AF assigned 1:1 to PVI by contact-force sensing, irrigated radiofrequency catheter, or second-generation cryoballoon catheter. Implantable cardiac monitors were inserted ≥1 month before PVI for assessment of AF burden and recurrence, and all patients, irrespective of AF recurrence, underwent a second procedure 4 to 6 months after PVI to determine PVI durability.

Results:

In the second procedure, 152 out of 199 (76%) pulmonary veins (PVs) were found durably isolated after RF and 161 out of 200 (81%) after CRYO (
P
=0.32), corresponding to durable isolation of all veins in 47% of patients in both groups (
P
=1.0). Median AF burden before PVI was 5.4% (interquartile range, 0.5%–13.0%) versus 4.0% (0.6%–18.1%), RF versus CRYO (
P
=0.71), and reduced to 0.0% (0.0%–0.1%) and 0.0% (0.0%–0.5%), respectively (
P
=0.58)—a reduction of 99.9% (92.9%–100.0%) and 99.3% (85.9%–100.0%;
P
=0.36). AF burden after PVI significantly correlated to the number of durably isolated PVs (
P
<0.01), but 9 out of 45 (20%) patients with durable isolation of all veins had recurrence of AF within 4 to 6 months after PVI (excluding a 3-month blanking period).

Conclusions:
PVI by RF and CRYO produce similar moderate to high PVI durability. Both treatments lead to marked reductions in AF burden, which is related to the number of durably isolated PVs. However, for one-fifth of paroxysmal AF patients, complete and durable PVI was not sufficient to prevent even short-term AF recurrence.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03805555.
<p><strong>Nomenclatural remarks in the genus <em>Melocactus</em> (Cactaceae, Cereeae) from NE Brazil </strong></p>
Authors: GUIGGI ALESSANDRO , MARIOTTI MAURO 
Published: April 2021

As part of the ongoing study on Brazilian Cacti (see e.g., Guiggi 2020a, 2020b), we here present a note about two taxa belonging to the genus Melocactus Link & Otto (1827: 417), i.e. Melocactus pachycephalus N.P.Taylor (in Taylor & Zappi 2020: 256) and M. alex-bragae P.J.Braun & Esteves (2008: 252).
Risk Assessment in Thyroid Lobectomy and Total Thyroidectomy using Over 100 Thousand Cases
Authors: Brauer Philip R. , Burkey Brian B. , Reddy Chandana A. , Lamarre Eric D. 
Published: April 2021

Objectives: To assess risk factors and non-thyroid specific postoperative complications for thyroid lobectomy compared to total thyroidectomy. Methods: A retrospective, cross-sectional study of adults undergoing a lobectomy or total thyroidectomy using the National Surgical Quality Improvement Program database between 2005 and 2017. Patients not treated by otolaryngologists or general surgeons and with unknown demographic variables were excluded. Results: A total of 106 915 patients were analyzed, 64 763 total thyroidectomies and 42 152 lobectomies. Multivariable analysis demonstrated that total thyroidectomy patients were half as likely to return to the operating room (OR = 0.491 (95%CI 0.445-0.542), P < .001). Within this cohort, patients at greater risk for reoperation had a history of hypertension (OR = 1.225 (95%CI 1.090-1.376), P < .001), a malignant pathology (OR = 1.921 (95%CI 1.734-2.128), P < .001), and smoked (OR = 1.237 (95%CI 1.087-1.407), P = .001). Conversely, diabetes and body mass index did not impact the rate of reoperation when assessing total thyroidectomy and lobectomy. The most frequent non-thyroid specific complications in total thyroidectomy were unplanned intubation (0.5%), urinary tract infection (0.3%), and superficial surgical site infection (0.3%). In thyroid lobectomy, the most common complications were superficial surgical site infection (0.3%) and urinary tract infection (0.2%). Conclusions: Our multi-institutional study indicates specific risk factors for returning to the operating room that may warrant closer follow up after surgery for total thyroidectomy or thyroid lobectomy. We also identified the most common post-operative complications. During pre-operative planning, these findings should be considered by thyroid surgeons to help mitigate risk to patients.
Dural Contact to the Malleus Head in Patients with Superior Semicircular Canal Dehiscence (SSCD): Case Series and Review of SSCD and Tegmen Defects
Authors: Wentland Carissa , Cousins Joseph , May Jason , Rivera Arnaldo 
Published: April 2021

Objective: Report a series of cases in which patients have concomitant superior semicircular canal dehiscence (SSCD) and a dehiscent tegmen tympani with Dural contact to the malleus head (DCMH). Methods: An analysis of radiologic and audiologic data in 4 patients who presented with SSCD and DCMH at a tertiary care institution. A pertinent literature review was performed. Results: Four patients (5 ears) had SSCD and DCMH. In 3 patients with unilateral DCMH, the mean maximum air-bone gap was 15 dB in the ear with DCMH compared to 50 dB in the ear without DCMH. Of the 5 ears with DCMH, the mean air conduction threshold at 250 Hz was 17 dB compared to 42 dB in the 3 ears without DCMH. Conclusions: We report the findings of DCMH in a series of 4 patients with bilateral SSCD. This limited series suggests that ears with SSCD and DCMH have less of an air-bone gap than would be expected, as 1 would expect an additive effect of DCMH and SSCD on the air-bone gap.
Feel the Burn! Fireworks-related Otolaryngologic Trauma
Authors: Straughan Alexander J. , Pasick Luke J. , Gupta Vrinda , Benito Daniel A. , Goodman Joseph F. , Zapanta Philip E. 
Published: April 2021

Objectives: Fireworks are used commonly for celebrations in the United States, but can lead to severe injury to the head and neck. We aim to assess the incidence, types, and mechanisms of head and neck injuries associated with fireworks use from 2010 to 2019. Methods: A retrospective cross-sectional study, using data from the National Electronic Injury Surveillance System, of individuals presenting to United States Emergency Departments with head and neck injuries caused by fireworks and flares from 2010 to 2019. Incidence, types, and mechanisms of injury related to fireworks use in the US population were assessed. Results: A total of 541 patients (349 [64.5%] male, and 294 [54%] under 18 years of age) presented to emergency departments with fireworks-related head and neck injuries; the estimated national total was 20 584 patients (13 279 male, 9170 white, and 11 186 under 18 years of age). The most common injury diagnoses were burns (44.7% of injuries), laceration/avulsion/penetrating trauma (21.1%), and otologic injury (15.2%), which included hearing loss, otalgia, tinnitus, unspecified acoustic trauma, and tympanic membrane perforation. The remaining 19% of injuries were a mix, including contusion, abrasion, hematoma, fracture, and closed head injury. Associations between fireworks type and injury diagnosis (chi-square P < .001), as well as fireworks type by age group (chi-square P < .001) were found. Similarly, associations were found between age groups and injury diagnoses (chi-square P < .001); these included children 5 years and younger and adults older than 30 years. Conclusions: Fireworks-related head and neck injuries are more likely to occur in young, white, and male individuals. Burns are the most common injury, while otologic injury is a significant contributor. Annual rates of fireworks-related head and neck injuries have not changed or improved significantly in the United States in the past decade, suggesting efforts to identify and prevent these injuries are insufficient.
To whose good? Directions and gaps in psychiatric research
Authors: Wigand Moritz E , Wiegand Hauke F , Scherp Ansgar , Becker Thomas 
Published: April 2021

Background: Psychiatry’s evidence-, implementation-, and treatment-gaps. Aims: The aim of this study is to uncover current trends and gaps in psychiatric research. Understanding where psychiatric research is going and where there might be blind spots is important to better align it with global mental health challenges and with service users’ needs. Method: 10 top-ranking scientific journals (highest impact factors) in psychiatry were identified for 3 years (1999, 2009, 2019) using Clarivate Analytics. Metadata of all papers published by these journals in the index years were downloaded, and the relevance and relatedness of terms from all titles and abstracts were computed and visualized using VOSviewer. Results: In 1999, prominent themes included schizophrenia and novel antipsychotics as well as research on families. Ten and 20 years later, neurobiological research, especially genetic and animal studies, had gained importance. Social and psychological themes were less present across all three time points. Conclusions: In high-ranking psychiatric journals, neurobiological research appears to gain importance while social themes are under-represented. In view of challenges such as implementation gaps, marginalization of people with severe mental illness and mental health risks through social inequality, there seems to be a dissociation between research and patient needs. We suggest a systems approach to bring together different kinds of knowledge.
Subconcussive Head Impacts and Neurocognitive Function Over 3 Seasons of Youth Football
Authors: Rose Sean C. , Yeates Keith Owen , Nguyen Joseph T. , Ercole Patrick M. , Pizzimenti Natalie M. , McCarthy Matthew T. 
Published: April 2021

Objective: To determine the association between repetitive subconcussive head impacts and neurobehavioral outcomes in youth tackle football players. Methods: Using helmet-based sensors, we measured head impacts for 3 consecutive seasons of play in 29 male players age 9-11. Cumulative impact g’s were calculated. Players completed a battery of outcome measures before and after each season, including neuropsychological testing, vestibular-ocular sensitivity, and self- and parent-reported measures of symptoms and attention-deficit hyperactivity disorder (ADHD). Results: Average cumulative impact over 3 seasons was 13 900 g. High-intensity hits predicted worse change for self-reported social adjustment ( P = .001). Cumulative impact did not predict change in any of the outcome measures. History of ADHD, anxiety, and depression predicted worse change for self-reported symptoms and social adjustment, independent of head impacts. When players were stratified into 3 groups based on cumulative impact across all 3 seasons, differences in outcome measures existed prior to the start of the first season. These differences did not further increase over the course of the 3 seasons. Conclusion: Over 3 consecutive seasons of youth tackle football, we found no association between cumulative head impacts and neurobehavioral outcomes. Larger sample sizes and longer follow-up times would further assist in characterizing this relationship.
The role of universities in regional development strategies: A comparison across actors and policy stages
Authors: Fonseca Liliana , Nieth Lisa 
Published: April 2021

The emergence of collaborative approaches in innovation policy and regional governance has increased expectations for universities to engage in strategy making and assume broader roles and responsibilities. Nonetheless, complexities inherent to the policy process, regional context and universities’ own institutional and organisational capacity are often ignored or under-explained when framing universities’ roles. Although these roles are frequently introduced, they have been superficially conceptualised in the literature. This study develops a deeper theoretical and empirical understanding of universities’ contributions in the different stages of regional innovation strategy processes. Through a comparative case study of four European universities, it explores the variation of these roles by policy stage and university actors involved in the strategies. Findings suggest universities have expanded to perform new planning-related roles (e.g. consultation, mediation) and that diverse factors (e.g. the regional context, such as urban versus peripheral) determine their participation in regional strategies. However, strategic coordination within universities and with regional bodies is needed for the optimisation of their engagement in the regional governance process. JEL Codes: I23, I25, O20, O30, R58
Migrating Souvenir Bullet: The Management Dilemma
Authors: Swain Srikant Kumar , Arora Rajnish Kumar , Mittal Radhe Shyam 
Published: April 2021

The cranio-cerebral trauma following gunshot injuries has high mortality and morbidity, with 66% to 90% victims dying before reaching hospital and only half of those treated in hospital surviving. However, in case of most salvageable patients, the question which poses dilemma to treating physicians is the decision as to when and why remove the retained missile. A 21-year-old man was observing a gunfight in the street from his balcony. Suddenly something struck his forehead and there was a small amount of bleeding toward the medial end of his left eyebrow. He had moderate headache and dizziness. Because of nonresolution of headache over seven days he was hospitalized and underwent X ray of the skull and CT of the head, which showed a retained metallic bullet in left inferior parieto-occipital region without any significant hemorrhage. As there was no neurological deficit or meningeal signs, he was managed conservatively. His symptoms improved gradually within next week and he was discharged home. His most recent follow-up was 28 months since injury and imaging showed migration of the bullet to the right inferior temporal region. As he was completely asymptomatic throughout, no intervention was offered. However, long-term follow-up for potential complications of migration, hydrocephalus, and abscess formation is advisable.
The study of dry eye and meibomian glands in psoriasis
Authors: Taheri Ahmad Reza , Allahyari Elahe , Zeinaly Mostafa , Nikandish Malihe 
Published: April 2021

Background: To investigate aqueous and lipid layers of the tear film as well as meibomian gland structure by meibography in psoriatic patients in the Iranian population. Methods: This case-control study was conducted on 31 psoriasis patients and 31 controls in Birjand University of Medical Sciences in 2018. The sampling method was available from the date of approval of the proposal in the Ethics Committee until it reached the sample size. After entering the study, patients were examined individually with a slit lamp. Then, Ocular Surface Disease Index (OSDI) score assessment, Schirmer test 1, lacrimal measurement with SM tube, tear break-up time (TBUT), and meibomian glands imaging by SBM Sistemi were done. Finally, the obtained data were entered into SPSS 15 software and analyzed at a significant level of less than 0.05. Results: The two groups were matched according to age and gender ( p = 0.39 and p = 0.80; respectively). With the exception of the SM Tube score, the mean of all tear film and meibomian glands functional and structural parameters including Schirmer test 1, TBUT, and meibography were significantly different between patients and control groups. Moreover, the proportion of abnormal OSDI (OSDI ⩾ 13) and the dry eye was significantly higher in psoriasis patients. Conclusions: Psoriasis is associated with dry eye as well as meibomian glands atrophy and dysfunction.
The impact of COVID-19 infection on hip fracture 30-day mortality
Authors: Fadulelmola Ahmed , Gregory Rob , Gordon Gavin , Smith Fiona , Jennings Andrew 
Published: April 2021

Introduction: A novel virus, SARS-CoV-2, has caused a fatal global pandemic which particularly affects the elderly and those with comorbidities. Hip fractures affect elderly populations, necessitate hospital admissions and place this group at particular risk from COVID-19 infection. This study investigates the effect of COVID-19 infection on 30-day hip fracture mortality. Method: Data related to 75 adult hip fractures admitted to two units during March and April 2020 were reviewed. The mean age was 83.5 years (range 65–98 years), and most (53, 70.7%) were women. The primary outcome measure was 30-day mortality associated with COVID-19 infection. Results: The COVID-19 infection rate was 26.7% (20 patients), with a significant difference in the 30-day mortality rate in the COVID-19-positive group (10/20, 50%) compared to the COVID-19-negative group (4/55, 7.3%), with mean time to death of 19.8 days (95% confidence interval: 17.0–22.5). The mean time from admission to surgery was 43.1 h and 38.3 h, in COVID-19-positive and COVID-19-negative groups, respectively. All COVID-19-positive patients had shown symptoms of fever and cough, and all 10 cases who died were hypoxic. Seven (35%) cases had radiological lung findings consistent of viral pneumonitis which resulted in mortality (70% of mortality). 30% ( n = 6) contracted the COVID-19 infection in the community, and 70% ( n = 14) developed symptoms after hospital admission. Conclusion: Hip fractures associated with COVID-19 infection have a high 30-day mortality. COVID-19 testing and chest X-ray for patients presenting with hip fractures help in early planning of high-risk surgeries and allow counselling of the patients and family using realistic prognosis.
A feasibility randomised controlled trial of targeted oxygen therapy in mechanically ventilated critically ill patients
Authors: Martin Daniel S , McNeil Margaret , Brew-Graves Chris , Filipe Helder , O’Driscoll Ronan , Stevens Jia Liu , Burnish Rachel , Cumpstey Andrew F , Williams Norman R , Mythen Michael G , Grocott Michael PW 
Published: April 2021

Background Despite oxygen being the commonest drug administered to critically ill patients we do not know which oxygen saturation (SpO2) target results in optimal survival outcomes in those receiving mechanical ventilation. We therefore conducted a feasibility randomised controlled trial in the United Kingdom (UK) to assess whether it would be possible to host a larger national multi-centre trial to evaluate oxygenation targets in mechanically ventilated patients. Methods We set out to recruit 60 participants across two sites into a trial in which they were randomised to receive conservative oxygenation (SpO2 88–92%) or usual care (control – SpO2 ≥96%). The primary outcome was feasibility; factors related to safety and clinical outcomes were also assessed. Results A total of 34 patients were recruited into the study until it was stopped due to time constraints. A number of key barriers to success were identified during the course of the study. The conservative oxygenation intervention was feasible and appeared to be safe in this small patient cohort and it achieved wide separation of the median time-weighted average (IQR) SpO2 at 91% (90–92%) in conservative oxygenation group versus 97% (96–97%) in control group. Conclusion Whilst conservative oxygenation was a feasible and safe intervention which achieved clear group separation in oxygenation levels, the model used in this trial will require alterations to improve future participant recruitment rates in the UK.