bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of serotonin‐5‐HTR1E signaling pathways and its role in cell survival
Authors: Sharma Vinay Kumar , Campbell Kiersten , Yang Xuyu , Dale Ryan , Loh Y. Peng 
Published: April 2023

Abstract5‐Hydroxytryptamine receptor 1E (5‐HTR1E) is reported to activate cyclic AMP (cAMP) and extracellular‐signal related kinases (ERK) pathways via its ligands and binding partners, but the detailed mechanism underlying the serotonin‐induced 5‐HTR1E signaling is still not known. In the present study, we determined the cellular regulators of ERK and cAMP signaling pathways in response to serotonin‐induced 5‐HTR1E activation in 5‐HTR1E overexpressing HEK293 cells. We found that Pertussis Toxin (PTX) treatment completely reversed the effect of serotonin‐5‐HTR1E mediated signaling on cAMP and ERK pathways, confirming the involvement of a Gαi‐linked cascade. We also observed that Gβγ and Gq were not associated with 5‐HTR1E activation, while blocking protein kinase A (PKA) inhibited ERK signaling only, and had no effect on cAMP. Additionally, serotonin‐stimulated ERK1/2 phosphorylation was similar in 5‐HTR1E overexpressing, β‐arrestin‐deficient HEK293 cells and is solely dependent on G protein signaling. siRNA mediated gene knockdown studies in SH‐SY5Y cells revealed that the inhibition of 5‐HTR1E reduced the expression of cMyc, Cyclin D1, Cyclin E and BCL2 genes which are related to cell cycle regulation and survival. MTT assays showed that 5‐HTR1E knockdown in SHSY‐5Y and U118 cells inhibited cell survival significantly. In addition to the signaling mechanism, we also performed RNA‐seq analysis in 5‐HTR1E overexpressing HEK293 cells and found that 5‐HTR1E can regulate the expression of Receptor activity modifying protein 1 (RAMP1), Nuclear receptor 1 (NR4A1) and other Cyclin genes. These findings indicate that serotonin interaction with 5‐HTR1E receptor simultaneously activates cAMP and ERK pathway in HEK293 cells and its expression is important for cell survival.
Severe Maternal Morbidity and Postpartum Readmission Through 1 Year
Authors: Druyan Brian , Platner Marissa , Jamieson Denise J. , Boulet Sheree L. 
Published: April 2023

OBJECTIVE:
To conduct a cohort study to estimate risk for readmission through 1 year postpartum and the most common readmission diagnoses for individuals with and without severe maternal morbidity (SMM) at delivery.

METHODS:
Using national health care claims data from IBM MarketScan Commercial Research Databases (now known as Merative), we identified all delivery hospitalizations for continuously enrolled individuals 15–49 years of age that occurred between January 1, 2016, and December 31, 2018. Severe maternal morbidity at delivery was identified using diagnosis and procedure codes. Individuals were followed for 365 days after delivery discharge, and cumulative readmission rates were calculated for up to 42 days, up to 90 days, up to 180 days, and up to 365 days. We used multivariable generalized linear models to estimate adjusted relative risks (aRR), adjusted risk differences, and 95% CIs for the association between readmission and SMM at each of the timepoints.

RESULTS:
The study population included 459,872 deliveries; 5,146 (1.1%) individuals had SMM during the delivery hospitalization, and 11,603 (2.5%) were readmitted within 365 days. The cumulative incidence of readmission was higher in individuals with SMM than those without at all timepoints (within 42 days: 3.5% vs 1.2%, aRR 1.44, 95% CI 1.23–1.68; within 90 days: 4.1% vs 1.4%, aRR 1.46, 95% CI 1.26–1.69); within 180 days: 5.0% vs 1.8%, aRR 1.48, 95% CI 1.30–1.69; within 365 days: 6.4% vs 2.5%, aRR 1.44, 95% CI 1.28–1.61). Sepsis and hypertensive disorders were the most common reason for readmission within 42 and 365 days for individuals with SMM (35.2% and 25.8%, respectively).

CONCLUSION:
Severe maternal morbidity at delivery was associated with increased risk for readmission throughout the year after delivery, a finding that underscores the need for heightened awareness of risk for complications beyond the traditional 6-week postpartum period.
Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study*
Authors: Wetterslev Mik , Hylander Møller Morten , Granholm Anders , Hassager Christian , Haase Nicolai , Lange Theis , Myatra Sheila N. , Hästbacka Johanna , Arabi Yaseen M. , Shen Jiawei , Cronhjort Maria , Lindqvist Elin , Aneman Anders , Young Paul J. , Szczeklik Wojciech , Siegemund Martin , Koster Thijs , Aslam Tayyba Naz , Bestle Morten H. , Girkov Mia S. , Kalvit Kushal , Mohanty Rakesh , Mascarenhas Joanne , Pattnaik Manoranjan , Vergis Sara , Haranath Sai Praveen , Shah Mehul , Joshi Ziyokov , Wilkman Erika , Reinikainen Matti , Lehto Pasi , Jalkanen Ville , Pulkkinen Anni , An Youzhong , Wang Guoxing , Huang Lei , Huang Bin , Liu Wei , Gao Hengbo , Dou Lin , Li Shuangling , Yang Wanchun , Tegnell Emily , Knight Agnes , Czuczwar Miroslaw , Czarnik Tomasz , Perner Anders ,   the AFIB-ICU Collaborators
Published: April 2023

OBJECTIVES:
To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF.

DESIGN:
Multicenter, prospective, inception cohort study.

SETTING:
Forty-four ICUs in 12 countries in four geographical regions.

SUBJECTS:
Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8–17.6), of which newly developed AF was 13.3% (11.5–15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16–23), magnesium 16% (13–20), potassium 15% (12–19), amiodarone 51% (47–55), beta-1 selective blockers 34% (30–38), calcium channel blockers 4% (2–6), digoxin 16% (12–19), and direct current cardioversion in 4% (2–6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95–1.99).

CONCLUSIONS:
In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.
Association of Optic Nerve Head and Macular Optical Coherence Tomography Measures With Glaucoma-Related Disability
Authors: Bonham Luke W. , Mihailovic Aleksandra , Xiao Grace , West Sheila K. , Friedman David S. , Ramulu Pradeep Y. 
Published: April 2023

Précis:
Optical coherence tomography (OCT) estimated retinal nerve fiber layer (RNFL) thickness associated with glaucoma-related disability independent of the visual field (VF) damage and thus may provide additional patient-relevant disability information beyond what is captured by standard VF testing.

Purpose:
To examine whether OCT metrics [peripapillary RNFL thickness and macular ganglion cell/inner plexiform layer (GCIPL) thickness] are associated with quality of life (QoL) measures and additional disability metrics, and whether these associations are independent of VF damage.

Methods:
In this cross-sectional study, 156 patients with glaucoma or suspected glaucoma received VF testing and OCT scans to measure RNFL and GCIPL thickness. QoL was assessed using the Glaucoma Quality-of-Life 15 and additional disability measures including fear of falling, reading speed, and steps per day were assessed. Multivariable regression models adjusting for relevant covariates tested whether RNFL or GCIPL thickness from the less-impaired eye were associated with disability measures and whether associations were independent of VF damage.

Results:
Greater VF damage is associated with worse QoL (95% CI=0.4–1.4; P<0.001) and slower reading speed (CI=−0.06 to −0.02; P<0.001). Lower RNFL and GCIPL thicknesses were associated with lower QoL scores, but not with QoL scores or other disability metrics after correcting for VF damage. However, post hoc analyses in patients with better eye thicknesses between 55 and 75 µm demonstrated associations between lower RNFL thickness and worse QoL (CI=−2.2 to −0.1; P=0.04) and greater fear of falling (CI=−6.1 to −0.4; P=0.03) even after accounting for VF damage. No such associations were observed for GCIPL thickness.

Conclusions:
OCT RNFL, but not GCIPL, thickness is associated with multiple disability measures independent of VF damage severity.
Clinical and Virologic Impacts of Respiratory Viral Co-infections in Children With Influenza
Authors: Sato Masatoki , Takashita Emi , Katayose Masahiko , Nemoto Kenji , Sakai Nobuko , Fujisaki Seiichiro , Hashimoto Koichi , Hosoya Mitsuaki 
Published: April 2023

Background:
Advances in multiplex polymerase chain reaction (PCR) methods have enabled the simultaneous detection of multiple respiratory viruses. We aimed to estimate the clinical and virologic impacts of influenza and other respiratory virus co-infection in children.

Methods:
We enrolled 38 and 35 children diagnosed with influenza and treated with baloxavir marboxil (baloxavir) and oseltamivir, respectively. We performed quantitative reverse transcription-PCR to detect and measure the levels of noninfluenza viruses from 3 nasopharyngeal swab samples collected before and on days 3 and 5 after the initial antiviral dose. We assessed patients’ clinical information using questionnaires.

Results:
One or more respiratory viruses other than influenza virus were detected in 26 (35.6%) of 73 children before antiviral treatment. The influenza virus load and clinical characteristics on the day of influenza onset were similar between children with and without virus co-infections. Of the 26 and 32 children without the emergence of the reduced baloxavir and oseltamivir susceptible variants after treatment, 8 (30.8%) and 7 (21.9%) children were dually co-infected with human rhinovirus only, respectively. The level of human rhinovirus RNA on day 0 in these children was less than −3 log10 that of influenza virus RNA, and the human rhinovirus co-infection had no impact on the disease course either clinically or virologically.

Conclusions:
When multiple respiratory viruses are detected in the same patient, it is necessary to assess clinical symptoms as well as the levels of detected viruses to determine which virus contributes to the development of illness.
Catheter-related Aspergillus Fungemia: Case Report and Literature Review
Authors: Kaur Ishminder , de St Maurice Annabelle 
Published: April 2023

Background:

Aspergillus fungemia is encountered infrequently in clinical practice, even in the setting of invasive and disseminated disease. Prolonged Aspergillus fungemia secondary to a central venous catheter is notably rarer.

Methods:
We describe the case of a 13-year-old boy with Aspergillus fungemia in the setting of a central venous catheter who was found to have pulmonary aspergillosis upon evaluation. We reviewed the literature for published cases of catheter-related Aspergillus fungemia and summarized the findings. We also sought to differentiate true fungemia from pseudofungemia and explored the clinical significance of aspergillemia.

Results:
We found 6 published cases of catheter-related Aspergillus fungemia in addition to the 1 discussed in this report. Based on the review of case findings, we propose an algorithm for an approach to a patient with a positive blood culture for Aspergillus spp.

Conclusions:
True aspergillemia is infrequent even in the setting of disseminated aspergillosis among immunocompromised patients and the presence of aspergillemia does not necessarily portend more severe clinical disease course. The management of aspergillemia should involve a determination of the possibility of contamination, and if deemed genuine, a thorough workup to define the extent of the disease process. Treatment durations should be based on tissue sites of involvement and could be shorter in the absence of tissue-invasive disease.
Echocardiography in shock
Authors: Chew Michelle S. , Aissaoui Nadia , Balik Martin 
Published: April 2023

Purpose of review
The aim of this study was to illustrate the varying roles of echocardiography in all phases of shock ranging from a rapid, diagnostic tool at the bedside, to a tool for monitoring the adequacy and effects of shock treatment and finally for identification of patients suitable for de-escalation of therapy.

Recent findings
Echocardiography has become an indispensable tool for establishing diagnosis in patients with shock. It is also important for assessing the adequacy of treatment such as fluid resuscitation, vasopressors and inotropes by providing integrated information on cardiac contractility and systemic flow conditions, particularly when used in conjunction with other methods of advanced haemodynamic monitoring. Apart from a traditional, diagnostic role, it may be used as an advanced, albeit intermittent, monitoring tool. Examples include the assessment of heart-lung interactions in mechanically ventilated patients, fluid responsiveness, vasopressor adequacy, preload dependence in ventilator-induced pulmonary oedema and indications for and monitoring during extracorporeal life support. Emerging studies also illustrate the role of echocardiography in de-escalation of shock treatment.

Summary
This study provides the reader with a structured review on the uses of echocardiography in all phases of shock treatment.
Which haemodynamic monitoring should we chose for critically ill patients with acute circulatory failure?
Authors: Monnet Xavier , Lai Christopher 
Published: April 2023

Purpose of review
To discuss the suitable haemodynamic monitoring for critically ill patients with shock.

Recent findings
For the basic initial monitoring, recent studies emphasized the importance of clinical signs of hypoperfusion and arterial pressure. This basic monitoring is not sufficient in patients resisting to initial treatment. Echocardiography does not allow multidaily measurements and has limitations, for measuring right or left ventricular preload. For a more continuous monitoring, noninvasive and minimally invasive tools are insufficiently reliable, as recently confirmed, and informative. The most invasive techniques, transpulmonary thermodilution and the pulmonary arterial catheter are more suitable. Their effect on outcome is lacking, although recent studies showed their benefit in acute heart failure. For assessing tissue oxygenation, recent publications better defined the meaning of the indices derived from the partial pressure of carbon dioxide. The integration of all data by artificial intelligence is the subject of early research in critical care.

Summary
For monitoring critically ill patients with shock, minimally or noninvasive systems are not reliable or informative enough. In the most severe patients, a reasonable monitoring policy can combine continuous monitoring by transpulmonary thermodilution systems or the pulmonary arterial catheter, with an intermittent assessment with ultrasound and measurement of tissue oxygenation.
Exceptional Response of Pancreatic Acinar Cell Carcinoma and Bile Duct Cancer to Platinum-Based Chemotherapy in a Family With a Germline BRCA2 Variant
Authors: Sunami Tomohiko , Yamada Atsushi , Kondo Tomohiro , Kanai Masashi , Nagai Kazuyuki , Uchida Yoichiro , Yokode Masataka , Matsumori Tomoaki , Uza Norimitsu , Murakami Hiromi , Yamada Takahiro , Muto Manabu 
Published: April 2023

Abstract
Pancreatic cancer and its rare subtype, acinar cell carcinoma (PACC), frequently harbor germline and/or somatic variants in homologous recombinant genes, including BRCA2. Individuals possessing germline pathogenic BRCA2 variants are known to have a higher risk of developing various cancers, including breast, ovarian, pancreatic, and bile duct cancers (BDCs). It has been reported that tumors positive for BRCA1/2 variants are sensitive to platinum-based agents. Thus, BRCA1/2 germline testing and comprehensive genomic profiling are recommended to identify genetic susceptibility and to indicate optimal targeted therapy. Here, we report familial occurrence of PACC and BDC associated with BRCA2; both tumors responded exceptionally well to platinum-based chemotherapy. A 37-year-old man was diagnosed with unresectable PACC with a germline BRCA2 variant. He was treated with oxaliplatin-containing chemotherapy and conversion surgery, and remains alive without tumor recurrence after more than 36 months. His father also possessed the identical germline BRCA2 variant and was diagnosed with extrahepatic BDC with lymph node metastases. The tumors showed marked shrinkage upon treatment with cisplatin-containing chemotherapy. Our cases underscore the importance of comprehensive genomic profiling and genetic testing for BRCA2 to ensure optimal therapeutic options for PACC as well as to identify high-risk individuals with various cancers in the family.
New-Onset Diabetes Is a Potential Marker for the Malignant Transformation of Pancreatic Cysts
Authors: Schweber Adam B. , Agarunov Emil , Brooks Christian , Hur Chin , Gonda Tamas A. 
Published: April 2023

Objectives
New-onset diabetes mellitus has been shown to be associated with pancreatic cancer (PC) in the general population. Our objective was to leverage real-world data to assess the association of new-onset diabetes (NODM) with malignant transformation in a large longitudinal cohort of pancreatic cyst patients.

Methods
A retrospective longitudinal cohort study was conducted using IBM's MarketScan claims databases from 2009 to 2017. From 200 million database subjects, we selected patients with newly diagnosed cysts without prior pancreatic pathology.

Results
Of the 137,970 patients with a pancreatic cyst, 14,279 had a new diagnosis. Median follow-up was 41.6 months. Patients with NODM progressed to PC at nearly 3 times the rate of patients without a diabetes history (hazard ratio, 2.80; 95% confidence interval, 2.05–3.83) and at a significantly higher rate than patients with preexisting diabetes (hazard ratio, 1.59; 95% confidence interval, 1.14–2.21). The mean interval between NODM and cancer diagnosis was 7.5 months.

Conclusions
Cyst patients who developed NODM progressed to PC at 3 times the rate of nondiabetics and at a greater rate than preexisting diabetics. The diagnosis of NODM preceded cancer detection by several months. These results support the inclusion of diabetes mellitus screening in cyst surveillance algorithms.
Stent-Associated Infectious Complications After Pancreatoduodenectomies Can Be Prevented by Perioperative Antibiotic Therapy
Authors: Biesel Esther A. , Chikhladze Sophia , Ruess Dietrich A. , Hopt Ulrich T. , Fichtner-Feigl Stefan , Wittel Uwe A. 
Published: April 2023

Objectives
Perioperative morbidity after pancreatoduodenectomies is still high. One potentially responsible factor is the insertion of bile duct stents before surgery. In our single-center study, we evaluated the influence of preoperative bile duct stenting combined with perioperative antibiotic therapy versus primary surgery in carcinoma patients.

Methods
Clinical data of 973 patients undergoing pancreatoduodenectomy at the University Hospital Freiburg from 2002 to 2018 were explored retrospectively. Postoperative pancreatic fistula, delayed gastric emptying (DGE), and postpancreatectomy hemorrhage (PPH) were graded by current international definitions. Patients with pancreatic ductal adenocarcinoma or periampullary carcinoma were included.

Results
We included 634 patients of whom 372 (58.7%) were treated with preoperative bile duct stenting. No difference concerning postoperative pancreatic fistula was observed (P = 0.479). We found more wound infections (stent 18.4%, no stent 11.1%, P = 0.008) but a significantly lower rate of PPH and DGE in stented patients (PPH 7.5% vs 11.9%, P = 0.044; DGE 16.5% vs 22.5%, P = 0.039). Surprisingly, intra-abdominal abscesses were reduced in stented patients (9.4% vs 15.0%, P = 0.022), just as insufficiencies of the biliodigestive anastomosis (P = 0.021).

Conclusions
Perioperative antibiotic therapy seems to reduce the risk for severe intra-abdominal infectious complications in stent-bearing patients.
Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases
Authors: Mastracci Teresa L. , Apte Minoti , Amundadottir Laufey T. , Alvarsson Alexandra , Artandi Steven , Bellin Melena D. , Bernal-Mizrachi Ernesto , Caicedo Alejandro , Campbell-Thompson Martha , Cruz-Monserrate Zobeida , El Ouaamari Abdelfattah , Gaulton Kyle J. , Geisz Andrea , Goodarzi Mark O. , Hara Manami , Hull-Meichle Rebecca L. , Kleger Alexander , Klein Alison P. , Kopp Janel L. , Kulkarni Rohit N. , Muzumdar Mandar D. , Naren Anjaparavanda P. , Oakes Scott A. , Olesen Søren S. , Phelps Edward A. , Powers Alvin C. , Stabler Cherie L. , Tirkes Temel , Whitcomb David C. , Yadav Dhiraj , Yong Jing , Zaghloul Norann A. , Sander Maike , Pandol Stephen J. 
Published: April 2023

Abstract
The “Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases” Workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report summarizes the workshop proceedings. The goal of the workshop was to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into 6 major themes, including (a) Pancreas Anatomy and Physiology; (b) Diabetes in the Setting of Exocrine Disease; (c) Metabolic Influences on the Exocrine Pancreas; (d) Genetic Drivers of Pancreatic Diseases; (e) Tools for Integrated Pancreatic Analysis; and (f) Implications of Exocrine-Endocrine Crosstalk. For each theme, there were multiple presentations followed by panel discussions on specific topics relevant to each area of research; these are summarized herein. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of the normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.