bluuebunny/crossref_metadata_2025_split huggingface dataset:
ADAR1p110 promotes Enterovirus D68 replication through its deaminase domain and inhibition of PKR pathway
Authors: Zhang Kehan , Wang Siyuan , Chen Tingting , Tu Zeng , Huang Xia , Zang Guangchao , Wu Chun , Fan Xinyue , Liu Jia , Tian Yunbo , Cheng Yong , Lu Nan , Zhang Guangyuan 
Published: December 2022

Abstract
Background
Severe respiratory and neurological diseases caused by human enterovirus D68 (EV-D68) pose a serious threat to public health, and there are currently no effective drugs and vaccines. Adenosine deaminase acting on RNA1 (ADAR1) has diverse biological functions in various viral infections, but its role in EV-D68 infections remains undetermined.

Methods
Rhabdomyosarcoma (RD) and human embryonic kidney 293 T (293 T) cells, and HeLa cells were used to evaluate the expression level of ADAR1 upon EV-D68 (Fermon strain) and human parainfluenza virus type 3 (HPIV3; NIH47885) infection, respectively. Knockdown through silencing RNA (siRNA) and overexpression of either ADAR1p110 or ADAR1p150 in cells were used to determine the function of the two proteins after viral infection. ADAR1p110 double-stranded RNA binding domains (dsRBDs) deletion mutation was generated using a seamless clone kit. The expression of ADAR1, EV-D68 VP1, and HPIV3 hemagglutinin–neuraminidase (HN) proteins was identified using western blotting. The median tissue culture infectious dose (TCID50) was applied to detect viral titers. The transcription level of EV-D68 mRNA was analyzed using reverse transcription-quantitative PCR (RT-qPCR) and the viral 5′-untranslated region (5′-UTR)-mediated translation was analyzed using a dual luciferase reporter system.

Conclusion
We found that the transcription and expression of ADAR1 was inhibited upon EV-D68 infection. RNA interference of endogenous ADAR1 decreased VP1 protein expression and viral titers, while overexpression of ADAR1p110, but not ADAR1p150, facilitated viral replication. Immunofluorescence assays showed that ADAR1p110 migrated from the nucleus to the cytoplasm after EV-D68 infection. Further, ADAR1p110 lost its pro-viral ability after mutations of the active sites in the deaminase domain, and 5′-UTR sequencing of the viral genome revealed that ADAR1p110 likely plays a role in EV-D68 RNA editing. In addition, after ADAR1 knockdown, the levels of both phosphorylated double-stranded RNA dependent protein kinase (p-PKR) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α) increased. Attenuated translation activity of the viral genome 5′-UTR was also observed in the dual-luciferase reporter assay. Lastly, the deletion of ADAR1p110 dsRBDs increased the level of p-PKR, which correlated with a decreased VP1 expression, indicating that the promotion of EV-D68 replication by ADAR1p110 is also related to the inhibition of PKR activation by its dsRBDs. Our study illustrates that ADAR1p110 is a novel pro-viral factor of EV-D68 replication and provides a theoretical basis for EV-D68 antiviral research.
Non-interventional follow-up versus fluid bolus in RESPONSE to oliguria in hemodynamically stable critically ill patients: a randomized controlled pilot trial
Authors: Inkinen Nina , Pettilä Ville , Valkonen Miia , Serlo Maija , Bäcklund Minna , Hästbacka Johanna , Pulkkinen Anni , Selander Tuomas , Vaara Suvi T. 
Published: December 2022

Abstract
Background
Fluid bolus therapy is a common intervention to improve urine output. Data concerning the effect of a fluid bolus on oliguria originate mainly from observational studies and remain controversial regarding the actual benefit of such therapy. We compared the effect of a follow-up approach without fluid bolus to a 500 mL fluid bolus on urine output in hemodynamically stable critically ill patients with oliguria at least for 2 h (urine output < 0.5 mL/kg/h) in randomized setting.

Methods
We randomized 130 patients in 1:1 fashion to receive either (1) non-interventional follow-up (FU) for 2 h or (2) 500 mL crystalloid fluid bolus (FB) administered over 30 min. The primary outcome was the proportion of patients who doubled their urine output, defined as 2-h urine output post-randomization divided by urine output 2 h pre-randomization. The outcomes were adjusted for the stratification variables (presence of sepsis or AKI) using two-tailed regression. Obtained odds ratios were converted to risk ratios (RR) with 95% confidence intervals (CI). The between-group difference in the continuous variables was compared using mean or median regression and expressed with 95% CIs.

Results
Altogether 10 (15.9%) of 63 patients in the FU group and 22 (32.8%) of 67 patients in FB group doubled their urine output during the 2-h period, RR (95% CI) 0.49 (0.23–0.71), P = 0.026. Median [IQR] change in individual urine output 2 h post-randomization compared to 2 h pre-randomization was − 7 [− 19 to 17] mL in the FU group and 19[0–53] mL in the FB group, median difference (95% CI) − 23 (− 36 to − 10) mL, P = 0.001. Median [IQR] duration of oliguria in the FU group was 4 [2–8] h and in the FB group 2 [0–6] h, median difference (95%CI) 2 (0–4) h, P = 0.038. Median [IQR] cumulative fluid balance on study day was lower in the FU group compared to FB group, 678 [518–1029] mL versus 1071 [822–1505] mL, respectively, median difference (95%CI) − 387 (− 635 to − 213) mL, P < 0.001.

Conclusions
Follow-up approach to oliguria compared to administering a fluid bolus of 500 mL crystalloid in oliguric patients improved urine output less frequently but lead to lower cumulative fluid balance.
Trial registration clinical.trials.gov, NCT02860572. Registered 9 August 2016.

Graphical Abstract
Can we hit prenatal depression and anxiety through HIIT? The effectiveness of online high intensity interval training in pregnant women during the COVID-19 pandemic: a randomized controlled trial
Authors: Wilczyńska Dominika , Walczak-Kozłowska Tamara , Radzimiński Łukasz , Oviedo-Caro Miguel Ángel , Santos-Rocha Rita , Szumilewicz Anna 
Published: December 2022

Abstract
Background
In recent years high intensity interval training (HIIT) has grown in popularity. However, it rarely represents training interventions in experimental studies in pregnant populations. Therefore, in this study we aimed to assess changes in depressive symptoms, fear of childbirth, fear of Covid-19 and quality of life after an 8-week supervised online HIIT program, compared to an educational (self-performed physical activity) program.

Methods
We conducted a randomized control trial among 54 Caucasian women in uncomplicated, singleton pregnancy (age 32 ± 4 years, 22 ± 4 week of gestation; mean ± SD). There were 34 women in the experimental group, who participated in an 8-week high intensity interval training program (HIIT group). The comparative group was constituted of 20 pregnant women who attended 8-week educational program (EDU group).

Results
The most important finding was that mental health improved somewhat in both groups after the intervention, but only the HIIT group improved statistically significantly. The positive trends in lowering the severity of depressive symptoms, fear of childbirth, and fear of Covid-19 were observed in both groups. However, the positive response to the intervention was stronger in the EDU group. As a secondary outcome, there was a significant decrease in cardiorespiratory fitness level in the EDU group, while the HIIT group maintained unchanged level of maximal oxygen uptake.

Conclusions
HIIT seems to be beneficial for women with uncomplicated pregnancies to maintain adequate quality of life and mental health. However, more research is needed to determine the effectiveness of prenatal HIIT in pregnant women in various psychological conditions.
Trial registration: We conducted this study in Poland, in 2021. It was approved by the Bioethics Commission at the District Medical Chamber in Gdansk (KB-8/21). The full study protocol was registered in ClinicalTrials.gov (NCT05009433).
CSF tau368/total-tau ratio reflects cognitive performance and neocortical tau better compared to p-tau181 and p-tau217 in cognitively impaired individuals
Authors: Simrén Joel , Brum Wagner S. , Ashton Nicholas J. , Benedet Andrea L. , Karikari Thomas K. , Kvartsberg Hlin , Sjons Emma , Lussier Firoza Z. , Chamoun Mira , Stevenson Jenna , Hopewell Robert , Pallen Vanessa , Ye Keqiang , Pascoal Tharick A. , Zetterberg Henrik , Rosa-Neto Pedro , Blennow Kaj 
Published: December 2022

AbstractIntroductionCerebrospinal fluid (CSF) tau biomarkers are reliable diagnostic markers for Alzheimer’s disease (AD). However, their strong association with amyloid pathology may limit their reliability as specific markers of tau neurofibrillary tangles. A recent study showed evidence that a ratio of CSF C-terminally truncated tau (tau368, a tangle-enriched tau species), especially in ratio with total tau (t-tau), correlates strongly with tau PET tracer uptake. In this study, we set to evaluate the performance of the tau368/t-tau ratio in capturing tangle pathology, as indexed by a high-affinity tau PET tracer, as well as its association with severity of clinical symptoms.MethodsIn total, 125 participants were evaluated cross-sectionally from the Translational Biomarkers of Aging and Dementia (TRIAD) cohort (21 young, 60 cognitively unimpaired [CU] elderly [15 Aβ+], 10 Aβ+ with mild cognitive impairment [MCI], 14 AD dementia patients, and 20 Aβ− individuals with non-AD cognitive disorders). All participants underwent amyloid and tau PET scanning, with [18F]-AZD4694 and [18F]-MK6240, respectively, and had CSF measurements of p-tau181, p-tau217, and t-tau. CSF concentrations of tau368 were quantified in all individuals with anin-housesingle molecule array assay.ResultsCSF tau368 concentration was not significantly different across the diagnostic groups, although a modest increase was observed in all groups as compared with healthy young individuals (allP< 0.01). In contrast, the CSF tau368/t-tau ratio was the lowest in AD dementia, being significantly lower than in CU individuals (Aβ−,P< 0.001; Aβ+,P< 0.01), as well as compared to those with non-AD cognitive disorders (P< 0.001). Notably, in individuals with symptomatic AD, tau368/t-tau correlated more strongly with [18F]-MK6240 PET SUVR as compared to the other CSF tau biomarkers, with increasing associations being seen in brain regions associated with more advanced disease (isocortical regions > limbic regions > transentorhinal regions). Importantly, linear regression models indicated that these associations were not confounded by Aβ PET SUVr. CSF tau368/t-tau also tended to continue to become more abnormal with higher tau burden, whereas the other biomarkers plateaued after the limbic stage. Finally, the tau368/t-tau ratio correlated more strongly with cognitive performance in individuals with symptomatic AD as compared to t-tau, p-tau217 and p-tau181.ConclusionThe tau368/t-tau ratio captures novel aspects of AD pathophysiology and disease severity in comparison to established CSF tau biomarkers, as it is more closely related to tau PET SUVR and cognitive performance in the symptomatic phase of the disease.
Malnutrition screening and treatment in pediatric oncology: a scoping review
Authors: Franke Jessica , Bishop Chris , Runco Daniel V. 
Published: December 2022

Abstract
Background
Malnutrition and cachexia during pediatric cancer treatment worsen toxicity and quality-of-life. Clinical practice varies with lack of standard malnutrition definition and nutrition interventions. This scoping review highlights available malnutrition screening and intervention data in childhood cancer and the need for standardizing assessment and treatment.

Methods
Ovid Medline, CINAHL, and Cochrane Library were searched for studies containing malnutrition as the primary outcome with anthropometric, radiographic, or biochemical measurements. Secondary outcomes included validated nutritional assessment or screening tools. Two authors reviewed full manuscripts for inclusion. Narrative analysis was chosen over statistical analysis due to study heterogeneity.

Results
The search yielded 234 articles and 17 articles identified from reference searching. Nine met inclusion criteria with six nutritional intervention studies (examining appetite stimulants, nutrition supplementation, and proactive feeding tubes) and three nutritional screening studies (algorithms or nutrition support teams) each with variable measures and outcomes. Both laboratory evaluations (albumin, prealbumin, total protein) and body measurement (weight loss, mid-upper arm circumference) were used. Studies demonstrated improved weight, without difference between formula or appetite stimulant used. Screening studies yielded mixed results on preventing weight loss, weight gain, and survival.

Conclusion
Our review demonstrated a paucity of evidence for malnutrition screening and intervention in pediatric cancer treatment. While a variety of malnutrition outcomes, interventions, and screening tools exist, nutritional interventions increased weight and decreased complications. Screening tools decreased malnutrition risk and may improve weight gain. Potential age- and disease-specific nutritional benefits and toxicities also exist, further highlighting the benefit of standardizing malnutrition definitions, screening, and interventions.
Assessing the collection and reporting of patient-reported outcome data in interventional cancer trials: a single institution, retrospective systematic evaluation
Authors: Lidington Emma , Hogan Holly , Gandolfi Ann , Lawrence Jane , Younger Eugenie , Cho Helena , Peckitt Clare , Mohammed Kabir , Matharu Sheila , Scerri Lisa , Husson Olga , Cruickshank Susanne , Turner Rachel , Wedlake Linda 
Published: December 2022

Abstract
Background
To understand our performance with respect to the collection and reporting of patient-reported outcome (PRO) measure (PROM) data, we examined the protocol content, data completeness and publication of PROs from interventional trials conducted at the Royal Marsden NHS Foundation Trust (RM) and explored factors associated with data missingness and PRO publication.

Design
From local records, we identified closed, intervention trials sponsored by RM that opened after 1995 and collected PROMs as primary, secondary or exploratory outcomes. Protocol data were extracted by two researchers and scored against the SPIRIT-PRO (PRO protocol content checklist; score 0–100, higher scores indicate better completeness). For studies with locally held datasets, the information team summarized for each study, PRO completion defined as the number of expected (as per protocol) PRO measurements versus the number of actual (i.e. completed) PRO measurements captured in the study data set. Relevant publications were identified by searching three online databases and chief investigator request. Data were extracted and each publication scored against the CONSORT-PRO (PRO manuscript content checklist; scored as SPIRIT-PRO above). Descriptive statistics are presented with exploratory comparisons of point estimates and 95% confidence intervals.

Results
Twenty-six of 65 studies were included in the review. Nineteen studies had accessible datasets and 18 studies published at least one article. Fourteen studies published PRO results. Most studies had a clinical (rather than PRO) primary outcome (16/26). Across all studies, responses in respect of 35 of 69 PROMs were published. Trial protocols scored on average 46.7 (range 7.1–92.9) on the SPIRIT-PRO. Among studies with accessible data, half (10/19) had less than 25% missing measurements. Publications scored on average 80.9 (range 36–100%) on the CONSORT-PRO. Studies that published PRO results had somewhat fewer missing measurements (19% [7–32%] vs 60% [− 26 to 146%]). For individual PROMs within studies, missing measurements were lower for those that were published (17% [10–24%] vs 41% [18–63%]). Studies with higher SPIRIT-PRO scores and PROs as primary endpoints (13% [4–22%] vs 39% [10–58%]) had fewer missing measurements.

Conclusions
Missing data may affect publication of PROs. Extent of inclusion of SPIRIT-PRO protocol items and PROs as primary endpoints may improve data completeness. Preliminary evidence from the study suggests a future larger study examining the relationship between PRO completion and publication is warranted.
Mental health services in Egypt during the COVID-19 pandemic
Authors: Okasha Tarek , Rabie Menan , Shaker Nermine Mahmoud , Mohsen Nesreen , EL-Habiby Mahmoud , El-Gabry Dina Aly , Gaber Eman , Ali Nemat , Ali Mohamad , Sayed Maha 
Published: December 2022

Abstract
Background
The COVID-19 pandemic has irreversibly altered the medical landscape. Compromised mental health among medical staff and the general population has called for new patient approaches, therapies, and medical services, among which Telehealth features prominently.

Results
This paper discusses the structure, approach, and efficiencies of pandemic-related mental health services in Egypt and summarizes responses and initiatives launched by the government of Egypt. A particular focus on the General Secretariat of Mental Health and Addiction Treatment (GSMHAT)’s action plan as well as Ain Shams University’s hospital Okasha Institute of Psychiatry sheds light on localized responses to the pandemic’s psychological impact.

Conclusions
Data showcasing the several types of Telehealth employed are used to derive conclusions about the merits and challenges of emerging online treatments within the context of COVID-19.
ARC-7: Randomized phase 2 study of domvanalimab + zimberelimab ± etrumadenant versus zimberelimab in first-line, metastatic, PD-L1-high non-small cell lung cancer (NSCLC).
Authors: Johnson Melissa Lynne , Fox William , Lee Yun-Gyoo , Lee Ki Hyeong , Ahn Hee Kyung , Kim Young-Chul , Lee Kang-Yun , Lee Jong-Seok , He Xian , Park Christine , Pomponio Debbie , Dang Thao , Phuong Patrick Hoang , Nuyten Dimitry S. A. , Hegde Aparna Madhukeshwar , Joshi Rohit 
Published: December 2022

397600 Background: While PD-1 inhibitors demonstrated survival benefit compared to chemotherapy in patients (pts) with PD-L1-high, NSCLC, less than half of pts respond to monotherapy. Novel therapeutics or combinations are necessary to improve outcomes. Domvanalimab (D) is an Fc-silent humanized IgG1 monoclonal antibody (mAb) that blocks T cell Immunoglobulin and ITIM domain (TIGIT), thereby reducing immunosuppression of T/NK cells and promoting antitumor activity. Etrumadenant (E) is a selective dual antagonist of both A2a and A2b receptors (R) expressed on immune cells thereby reducing immunosuppressive extracellular adenosine. ARC-7 evaluates whether inhibition of TIGIT and adenosine pathways augments activity of zimberelimab (Z) (anti-PD-1 mAb) in pts with PD-L1-high NSCLC. Methods: ARC-7 (NCT04262856) is a randomized, open-label phase 2 clinical trial which enrolled treatment-naïve pts with Stage IV, squamous or non-squamous NSCLC with locally assessed high PD-L1 expression (TPS ≥ 50%), no EGFR or ALK alterations, and ECOG PS ≤1. Pts were randomized (1:1:1) to: Arm 1 (Z): Z 360 mg intravenously (IV) every 3 weeks (Q3W); Arm 2 (DZ): D 15 mg/kg IV Q3W + Z; Arm 3 (EDZ): E 150 mg orally once daily + DZ. Pts in Arm 1 with confirmed progression had the option to cross over to EDZ. Co-primary endpoints were overall response rate (ORR) and progression-free survival (PFS) per RECIST v1.1. Results: As of 31 August 2022, 149 pts received at least one dose of study treatment. Efficacy for this interim analysis included 133 pts randomized at least 13 weeks prior to data cut-off (ITT-13), allowing for ≥ 2 post-baseline scans. With median follow-up of 11.8 months (mo), D-containing arms, demonstrated improved ORR and PFS compared to Z. In the safety population, grade ≥3 treatment-emergent adverse events occurred in 58% (Z), 47% (DZ), and 52% (EDZ). All cases of rash were grade 1-2, manageable with topical corticosteroids, and more common in EDZ (Table). Conclusions: In the first published, randomized dataset evaluating an Fc-silent TIGIT mAb, both D containing arms demonstrated clinically meaningful improvement in ORR and PFS compared to Z. Treatment with Z, DZ and EDZ was well tolerated, and the safety profiles of D-containing arms were similar to Z. Ongoing phase 3 trials are evaluating DZ compared to standard of care in metastatic NSCLC. Clinical trial information: NCT04262856. [Table: see text]
Estimating today's cosmological constant via the Zel'dovich-holographic connection
Authors: Tello Pablo G. , Bini Donato , Kauffman Stuart , Succi Sauro 
Published: December 2022

Abstract
This letter proposes an approach to the vacuum energy and the cosmological constant (CC) paradox based on the Zel’dovich's ansatz, which states that the observable contribution to the vacuum energy density is given by the gravitational energy of virtual particle-antiparticle pairs, continually generated and annihilated in the vacuum state. The novelty of this work is the use of an ultraviolet cut-off length based on the holographic principle, which is shown to yield current values of the CC in semi-quantitative agreement with experimental observations.
Cervical Small Cell Neuroendocrine Carcinoma With Ectopic ACTH Secretion and Acute Pancreatitis
Authors: Patel Harshil , Kishlyansky David , Köbel Martin , Alshamma Zainab , Glaze Sarah , Ghaznavi Sana 
Published: December 2022

Abstract
Ectopic Cushing syndrome from a primary carcinoma of the cervix is an exceedingly rare phenomenon. The objective of this review is to describe our clinical case and summarize the clinical characteristics, investigations, and outcomes of all published cases. We describe a previously healthy 39-year-old woman presenting with abnormal uterine bleeding, leading to a diagnosis of stage IIIC1 small cell neuroendocrine carcinoma of the cervix, human papillomavirus-associated. She was treated with neoadjuvant chemotherapy, radical hysterectomy, adjuvant chemotherapy, and pelvic radiation. Unfortunately, she developed progressive disease with multifocal hepatic metastases and lesions in the para-aortic lymph nodes. Eighteen months after her initial diagnosis, she presented with severe Cushing syndrome and acute pancreatitis and died from a splenic artery pseudoaneurysm. A literature review identified 10 published cases of ectopic ACTH secretion in the setting of carcinoma of the cervix. The mean age of presentation was 40. The majority (70%) occurred in the small cell neuroendocrine variant. In 80% of patients, cushingoid features developed concomitantly or shortly after the discovery of metastatic disease; cushingoid features included new-onset hypertension (30% of patients), hyperglycemia (50%), and hypokalemia (50%). All 10 patients died of the disease with a median survival of 2.5 months (range, 1-10 months) from the time of presentation with Cushing syndrome. Carcinoma of the cervix is a rare cause of ectopic Cushing syndrome. Nevertheless, it should be considered as a source of ectopic ACTH secretion in all women, especially those presenting with gynecologic complaints. Despite surgical resection and systemic therapy, prognosis is poor.