bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutically Increasing MHC-I Expression Potentiates Immune Checkpoint Blockade
Authors: Gu Shengqing Stan , Zhang Wubing , Wang Xiaoqing , Jiang Peng , Traugh Nicole , Li Ziyi , Meyer Clifford , Stewig Blair , Xie Yingtian , Bu Xia , Manos Michael P. , Font-Tello Alba , Gjini Evisa , Lako Ana , Lim Klothilda , Conway Jake , Tewari Alok K. , Zeng Zexian , Sahu Avinash Das , Tokheim Collin , Weirather Jason L. , Fu Jingxin , Zhang Yi , Kroger Benjamin , Liang Jin Hua , Cejas Paloma , Freeman Gordon J. , Rodig Scott , Long Henry W. , Gewurz Benjamin E. , Hodi F. Stephen , Brown Myles , Liu X. Shirley 
Published: February 2021

Abstract

Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Here, we combined FACS-based genome-wide CRISPR screens with a data-mining approach to identify drugs that can upregulate MHC-I without inducing PD-L1. CRISPR screening identified TRAF3, a suppressor of the NFκB pathway, as a negative regulator of MHC-I but not PD-L1. The Traf3-knockout gene expression signature is associated with better survival in ICB-naïve patients with cancer and better ICB response. We then screened for drugs with similar transcriptional effects as this signature and identified Second Mitochondria-derived Activator of Caspase (SMAC) mimetics. We experimentally validated that the SMAC mimetic birinapant upregulates MHC-I, sensitizes cancer cells to T cell–dependent killing, and adds to ICB efficacy. Our findings provide preclinical rationale for treating tumors expressing low MHC-I expression with SMAC mimetics to enhance sensitivity to immunotherapy. The approach used in this study can be generalized to identify other drugs that enhance immunotherapy efficacy.

Significance:
MHC-I loss or downregulation in cancer cells is a major mechanism of resistance to T cell–based immunotherapies. Our study reveals that birinapant may be used for patients with low baseline MHC-I to enhance ICB response. This represents promising immunotherapy opportunities given the biosafety profile of birinapant from multiple clinical trials.
This article is highlighted in the In This Issue feature, p. 1307
Routine Use of Tenecteplase for Thrombolysis in Acute Ischemic Stroke
Authors: Zhong Cathy S. , Beharry James , Salazar Daniel , Smith Kelly , Withington Stephen , Campbell Bruce C.V. , Wilson Duncan , Le Heron Campbell , Mason Deborah , Duncan Roderick , Reimers Jon , Mein-Smith Frances , Diprose William K. , Barber P. Alan , Ranta Annemarei , Fink John N. , Wu Teddy Y. 
Published: February 2021

Background and Purpose:
In ischemic stroke, intravenous tenecteplase is noninferior to alteplase in selected patients and has some practical advantages. Several stroke centers in New Zealand changed to routine off-label intravenous tenecteplase due to improved early recanalization in large vessel occlusion, inconsistent access to thrombectomy within stroke networks, and for consistency in treatment protocols between patients with and without large vessel occlusion. We report the feasibility and safety outcomes in tenecteplase-treated patients.

Methods:
We performed a retrospective analysis of consecutive patients thrombolyzed with intravenous tenecteplase at 1 comprehensive and 2 regional stroke centers from July 14, 2018, to February 29, 2020. We report the baseline clinical characteristics, rates of symptomatic intracranial hemorrhage, and angioedema. These were then compared with patient outcomes with those treated with intravenous alteplase at 2 other comprehensive stroke centers. Multivariable mixed-effects logistic regression models were performed assessing the association of tenecteplase with symptomatic intracranial hemorrhage and independent outcome (modified Rankin Scale score, 0–2) at day 90.

Results:

There were 165 patients treated with tenecteplase and 254 with alteplase. Age (75 versus 74 years), sex (56% versus 60% male), National Institutes of Health Stroke Scale scores (8 versus 10), median door-to-needle times (47 versus 48 minutes), or onset-to-needle time (129 versus 130 minutes) were similar between the groups. Symptomatic intracranial hemorrhage occurred in 3 (1.8% [95% CI, 0.4–5.3]) tenecteplase patients compared with 7 (2.7% [95% CI, 1.1–5.7]) alteplase patients (
P
=0.75). There were no differences between tenecteplase and alteplase in the rates of angioedema (4 [2.4%; 95% CI, 0.7–6.2] versus 1 [0.4%; 95% CI, 0.01–2.2],
P
=0.08) or 90-day functional independence (100 [61%] versus 140 [57%],
P
=0.47), respectively. In mixed-effects logistic regression models, there was no significant association between thrombolytic choice and symptomatic intracranial hemorrhage (odds ratio tenecteplase, 0.62 [95% CI, 0.14–2.80],
P
=0.53) or functional independence (odds ratio tenecteplase, 1.20 [95% CI, 0.74–1.95],
P
=0.46).

Conclusions:
Routine use of tenecteplase for stroke thrombolysis was feasible and had comparable safety profile and outcome to alteplase.
Dabigatran or Aspirin in East Asian Patients With Embolic Stroke of Undetermined Source
Authors: Uchiyama Shinichiro , Toyoda Kazunori , Lee Byung-Chul , Liou Chia-Wei , Wong Lawrence Ka Sing , Grauer Claudia , Brueckmann Martina , Taniguchi Atsushi , Urano Yasuhisa , Easton J. Donald ,   on behalf of the RE-SPECT ESUS Investigators
Published: February 2021

Background and Purpose:
We assessed the outcomes of dabigatran versus aspirin in a prespecified subgroup analysis of East Asian patients with embolic stroke of undetermined source in the RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source).

Methods:
Patients with a recent embolic stroke of undetermined source were randomized to dabigatran (150 or 110 mg BID) or aspirin (100 mg QD). The primary efficacy outcome was recurrent stroke; the primary safety outcome was major bleeding. The East Asia cohort was compared with patients from all other countries (non-East Asia cohort).

Results:
Overall, 988 of 5390 patients (18%) were randomized in East Asia. During a median follow-up of 18.8 months, there was no statistically significant difference in recurrent stroke (hazard ratio, 0.65 [95% CI, 0.41–1.03]) or major bleeding (hazard ratio, 1.04 [95% CI, 0.57–1.91]) in East Asian patients receiving dabigatran versus aspirin. Death from any cause occurred more often in the dabigatran versus the aspirin group (hazard ratio, 3.98 [95% CI, 1.32–12.01]).

Conclusions:
The treatment effect of dabigatran versus aspirin was consistent between cohorts, with no apparent superiority for dabigatran over aspirin in preventing recurrent stroke in patients with embolic stroke of undetermined source.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02239120.
Qualitative Study of Chinese Stroke Caregivers’ Caregiving Experience During the COVID-19 Pandemic
Authors: Lee Jung Jae , Tsang Wing Nga , Yang Sook Ching , Kwok Jojo Yan Yan , Lou Vivian W.Q. , Lau Kui Kai 
Published: February 2021

Background and Purpose:
The coronavirus disease 2019 (COVID-19) outbreak has led to disruptions in health care service delivery worldwide, inevitably affecting stroke survivors requiring ongoing rehabilitation and chronic illness management. To date, no published research has been found on stroke caregiving during the COVID-19 pandemic. This study aimed to explore Hong Kong stroke caregivers’ caregiving experiences in the midst of this difficult time.

Methods:
Individual semistructured interviews were conducted with 25 Chinese adult primary stroke caregivers from May to June 2020 via telephone. Interviews were transcribed verbatim and analyzed using an interpretive description approach and constant comparison strategy.

Results:
Five themes of the stroke caregiving experience during the COVID-19 pandemic emerged: care service adversities, additional caregiving workload and strain, threatened relationship between caregiver and stroke survivors, threats to caregivers’ physical and psychological well-being, and needs for continuing caregiving roles. Our findings suggested that caregivers have worsened physical and psychological well-being because of increases in care burden with simultaneously reduced formal and informal support. The relationship between caregiver and stroke survivor was subsequently affected, placing some survivors at heightened risk of abuse.

Conclusions:
Our study provides valuable findings about stroke caregiving experiences and needs during the pandemic. Delivery of psychological support, telemedicine, and household hygiene resources would be useful to mitigate caregivers’ psychological distress during the COVID-19 pandemic.
Territoriale Culten in West-Congo: Verdwijning of Transformatie?
Authors: Vanhee Hein 
Published: February 2021

Territorial Cults in West-Congo: Vanished or Transformed?
This paper discusses some of the key issues in my current research on the history of the relationship between society, tradition and Christianity in the west of Congo-Kinshasa over the last century. My focus here is on the process of progressive transformation of the nineteenth-century territorial cults and the structural continuity which is apparent in the development of the Congolese Christian church in the area. In presenting some of my working hypotheses I am suggesting that after an initial period of open hostility towards the first missionaries, BaKongo became aware – ‘empirically’ as it were – of the fact that new ways were to be explored in order to compete with the challenges of Western colonialism and the forces of modernity and globalisation. In this regard, the history of religious life in West Congo can be described as a progressive attempt to regain control over the relations between human society and the supernatural world.
Le President Mobutu et le Premier Ministre Sous L’acte Constitutionnel de la Transition: Duel ou Duo?
Authors: Esambo Kangashe Jean-Louis 
Published: February 2021

President Mobutu and the Prime Minister Under the Transitional Constitutional Act: Duel or Duo?
Since the beginning of the democratic process in Mobutu’s Zaire, in April 1990, a judicial and political debate has continued to divide the opinion on the power sharing within the executive.
The Transitional Constitutional Act, a result of the political negotiations of the Palais du Peuple, was aimed at resolving the competence conflicts between the President of the Republic and the Prime Minister. This constitutional framework, however, was unable to avoid neither the possibility of a “duel” nor the avatars of an alleged “duo” between the two main representatives of the executive function.
In the meantime, the frequent violations of the constitution by the head of state have shown that power sharing within a parliamentary system could not come to a compromise with the power practice under Mobutu.
Worlding Cinema
Authors: Gledhill Christine 
Published: February 2021

Abstract
Against the narrowly commercial and homogenising term ‘world cinema’ that lumps together a diversity of ‘foreign’ films as a category, the notion of ‘the local’ relativizes the idea of the ‘national’ as a singular entity. It suggests the pivoting around each other of ‘there’ and ‘here,’ thereby avoiding precisely fixed locations and calling on the dynamism of their relationship. The local, captures not only particular geo-political locations but historical relationships, which, interacting with changing conditions, produce the shifting frameworks of thinking, feeling, experience, and aesthetic perception that shape local practices, traditions, and cultural forms. However, this specificity is often called on to endorse an authenticity uncontaminated by metropolitan sophistication or global uniformity, enabling local products to travel to an elsewhere beyond national boundaries. The value of ‘world’ over ‘global’ lies in its call on the space shared by many different nationals, whereas ‘global’ suggests the homogenisation enforced by multi-national corporate and neo-colonial Western powers. As an alternative concept, ‘trans-national’ applied to cinema has the virtue of acknowledging the existence of nationally defined geo-historical and cultural differences as well as the reality of cross-border migration of personnel, technologies, and films, along with the complexity of international co-production. However, if the term keeps the idea of the ‘national’ in place, the boundaries it marks are neither natural nor fixed. If local film genres and narrative forms function as public sites in which aesthetic histories, cultural frames of reference and social experiences feed and negotiate with each other, the question arises how far the trans-national intensification of this activity now produces a new space for an emergent ‘world imaginary’: the idea of a shared ‘world’.
Numerical Simulation of Mountain Waves over the Southern Andes. Part II: Momentum Fluxes and Wave–Mean-Flow Interactions
Authors: Fritts David C. , Lund Thomas S. , Wan Kam , Liu Han-Li 
Published: February 2021

AbstractA companion paper by Lund et al. employed a compressible model to describe the evolution of mountain waves arising due to increasing flow with time over the southern Andes, their breaking, secondary gravity waves and acoustic waves arising from these dynamics, and their local responses. This paper describes the mountain wave, secondary gravity wave, and acoustic wave vertical fluxes of horizontal momentum, and the local and large-scale three-dimensional responses to gravity breaking and wave–mean-flow interactions accompanying this event. Mountain wave and secondary gravity wave momentum fluxes and deposition vary strongly in space and time due to variable large-scale winds and spatially localized mountain wave and secondary gravity wave responses. Mountain wave instabilities accompanying breaking induce strong, local, largely zonal forcing. Secondary gravity waves arising from mountain wave breaking also interact strongly with large-scale winds at altitudes above ~80 km. Together, these mountain wave and secondary gravity wave interactions reveal systematic gravity wave–mean-flow interactions having implications for both mean and tidal forcing and feedbacks. Acoustic waves likewise achieve large momentum fluxes, but typically imply significant responses only at much higher altitudes.
Synoptic–Dynamic and Airmass Characteristics Distinguishing Long- and Short-Duration Freezing Rain Events in the South-Central United States
Authors: McCray Christopher D. , Gyakum John R. , Atallah Eyad H. 
Published: February 2021

AbstractThough prolonged freezing rain events are rare, they can result in substantial damage when they occur. While freezing rain occurs less frequently in the south-central United States than in some regions of North America, a large number of extremely long-duration events lasting at least 18 h have been observed there. We explore the key synoptic–dynamic conditions that lead to these extreme events through a comparison with less severe short-duration events. We produce synoptic–dynamic composites and 7-day backward trajectories for parcels ending in the warm and cold layers for each event category. The extremely long-duration events are preferentially associated with a deeper and more stationary 500-hPa longwave trough centered over the southwestern United States at event onset. This trough supports sustained flow of warm, moist air from within the planetary boundary layer over the Gulf of Mexico northward into the warm layer. The short-duration cases are instead characterized by a more transient upper-level trough axis centered over the south-central U.S. region at onset. Following event onset, rapid passage of the trough leads to quasigeostrophic forcing for descent and the advection of cold, dry air that erodes the warm layer and ends precipitation. While trajectories ending in the cold layer are very similar between the two categories, those ending in the warm layer have a longer history over the Gulf of Mexico in the extreme cases compared with the short-duration ones, resulting in warmer and moister onset warm layers.
Acute diet soda consumption alters brain responses to food cues in humans: A randomized, controlled, cross-over pilot study
Authors: Farr Olivia M. 
Published: February 2021

Background: Diet soda consumption has frequently been linked to obesity and its comorbidities in epidemiological studies. Whether this link is causal and a potential mechanism remains to be determined. Aim/Methods: This randomized, cross-over, controlled pilot study sought to determine whether there may be changes in reward-related brain activations to visual food cues after acute consumption of diet soda versus regular soda or carbonated water using functional magnetic resonance imaging. Results: Diet soda as compared to carbonated water consumption increased activation of reward-related caudate to highly versus less desirable food cues. Diet soda as compared to regular soda increased reward-related insula and decreased activation of cognitive control-related dorsolateral prefrontal cortex to food cues versus non-food cues. No changes in ratings of hunger an hour after beverage consumption were observed. Conclusions: These results may suggest a potential mechanism for diet soda to increase food palatability through activation of the reward system and suppression of inhibitory control that remains to be confirmed by future studies.
Diagnostic capability of ultrasound in peritoneal catheter malfunction compared to videolaparoscopy
Authors: Zeiler Matthias , Federico Antonio , Lentini Paolo , Dell’Aquila Roberto , Santarelli Stefano , Granata Antonio ,   for the Project Group ‘Integrated Imaging and Interventional Nephrology’ of the Italian Society of Nephrology
Published: February 2021

Background: The approach to peritoneal catheter malfunction consists usually in a diagnostic and therapeutic sequence of laxative prescription, abdominal radiography, brushing of the catheter, guide-wire manipulation or fluoroscopy and in the end of a videolaparoscopy (VLS) rescue intervention. Ultrasound (US) is able to find out major causes of peritoneal catheter malfunction, however without a clearly defined diagnostic value. The aim of the study was to validate the diagnostic capability of US in catheter malfunction compared to the diagnostic reference of VLS. Methods: US scans of the subcutaneous and intraperitoneal segment of the catheter were performed prior to a VLS intervention in 40 adult patients presenting persistent catheter malfunction within a prospective multicentre study. Laxative prescription and brushing of the catheter lumen were undertaken prior to US scan. US diagnosis was compared to the corresponding at VLS, kappa coefficient calculated and the causes of mismatch analysed. Results: In US, causes of persistent malfunction were catheter dislocation combined with omental wrapping in 21 cases, omental wrapping without dislocation in 11 cases, dislocation only in 4 cases, adherences to non-omental structures in 3 cases and entrapment in the lateral inguinal fossa in 1 case. The US diagnosis corresponded to the respective at VLS in 36 of 40 cases, resulting in a kappa coefficient of 0.89 (95% CI: 0.78–1.00). The discrepancies were due to improper visualization of the catheter between omentum and intestinal loops, resulting in an erroneous US diagnosis of omental wrapping. Conclusions: This study suggests that US might have a pivotal role in the diagnostic approach to peritoneal catheter dysfunction.
Improvement of lupus-associated fatigue with modafinil: Report of two cases
Authors: Korsten Peter , Piantoni Silvia 
Published: February 2021

Fatigue is a frequently reported and disabling symptom in patients with systemic lupus erythematosus (SLE). The management of Lupus-associated fatigue (LAF) is complex and requires the exclusion of disease activity and comorbidities as potentially treatable causes. Standard of care recommendations includes psychological counselling and regular physical activity. However, many SLE patients still report the persistence of LAF despite these measures. Therefore, pharmacological management may be required, which has been insufficiently investigated in clinical trials. Here, we report two patients who improved with pharmacological treatment with modafinil (MODA), a central nervous system stimulant. Both patients had an overall low disease activity (SLEDAI-2K score of 0). Their FACIT fatigue scores were 15 and 20, respectively (with a maximum score of 52, where 52 indicates the best quality of life). With MODA treatment, the first patient’s FACIT fatigue score improved from 15 to 42, the second patient’s score from 20 to 37. In the latter patient, it returned to 21 after stopping the drug and increased back again to 37 after re-treatment. In conclusion, our report demonstrates, for the first time, that MODA treatment is a potential pharmacological treatment option in selected patients with LAF. Clinical trials in SLE are required to confirm our observations.
Help-seeking pathways prior to referral to outpatient child and adolescent mental health services
Authors: Hansen Anna Sofie , Kjaersdam Telléus Gry , Færk Emil , Mohr-Jensen Christina , Lauritsen Marlene Briciet 
Published: February 2021

Aim: To investigate parental help-seeking patterns prior to referral to outpatient child and adolescent mental health services (CAMHS), and whether type of symptoms or duration of mental health problems prior to referral influence help-seeking. Setting: Child mental health services in Denmark involve several sectors collaborating based on stepped-care principles. Access to CAMHS is free of charge but requires a formal referral. Methods: In this cross-sectional observational study, parents of 250 children were interviewed about pathways to outpatient CAMHS using the Children’s Services Interview. Results: The median parent-reported duration of mental health problems prior to referral to CAMHS was 6.0 (IQR 3.4–8.5) years for children referred for neurodevelopmental disorders compared to 2.8 (IQR 1.0–6.5) years for children referred for emotional disorders. Educational services were the first help-seeking contact for the majority (57.5%) but referrals to CAMHS were most frequently from healthcare services (56.4%), predominantly general practitioners. Educational services played a greater part in help-seeking pathways for children referred for neurodevelopmental disorders. Conclusion: The majority of children referred to CAMHS have mental health problems for years before referral. The delay in time-to-referral was most pronounced for children referred for neurodevelopmental disorders. Help-seeking pathways differ by symptom duration and type of symptoms.