bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prider: multiplexed primer design using linearly scaling approximation of set coverage
Authors: Smolander Niina , Julian Timothy R. , Tamminen Manu 
Published: May 2022

Abstract
Background
Designing oligonucleotide primers and probes is one of the key steps of various laboratory experiments such as multiplexed PCR or digital multiplexed ligation assays. When designing multiplexed primers and probes to complex, heterogeneous DNA data sets, an optimization problem can arise where the smallest number of oligonucleotides covering the largest diversity of the input dataset needs to be identified. Tools that provide this optimization in an efficient manner for large input data are currently lacking.

Results
Here we present Prider, an R package for designing primers and probes with a nearly optimal coverage for complex and large sequence sets. Prider initially prepares a full primer coverage of the input sequences, the complexity of which is subsequently reduced by removing components of high redundancy or narrow coverage. The primers from the resulting near-optimal coverage are easily accessible as data frames and their coverage across the input sequences can be visualised as heatmaps using Prider’s plotting function. Prider permits efficient design of primers to large DNA datasets by scaling linearly to increasing sequence data, regardless of the diversity of the dataset.

Conclusions
Prider solves a recalcitrant problem in molecular diagnostics: how to cover a maximal sequence diversity with a minimal number of oligonucleotide primers or probes. The combination of Prider with highly scalable molecular quantification techniques will permit an unprecedented molecular screening capability with immediate applicability in fields such as clinical microbiology, epidemic virus surveillance or antimicrobial resistance surveillance.
Antimicrobial activity of supernatants produced by bacteria isolated from Brazilian stingless bee’s larval food
Authors: Santos Ana Carolina Costa , Malta Serena Mares , Dantas Raquel Cristina Cavalcanti , Coelho Rocha Nina Dias , Ariston de Carvalho Azevedo Vasco , Ueira-Vieira Carlos 
Published: May 2022

Abstract
Background
The discovery of new molecules with antimicrobial properties has been a promising approach, mainly when related to substances produced by bacteria. The use of substances produced by bees has evidenced the antimicrobial action in different types of organisms. Thus, the use of bacteria isolated from larval food of stingless bees opens the way for the identification of the new molecules. The effect of supernatants produced by these bacteria was evaluated for their ability to inhibit the growth of bacteria of clinical interest. Furthermore, their effects were evaluated when used in synergy with antibiotics available in the pharmaceutical industry.

Results
A few supernatants showed an inhibitory effect against susceptible and multiresistant strains in the PIC assay and the modulation assay. Emphasizing the inhibitory effect on multidrug-resistant strains, 7 showed an effect on multidrug-resistant Escherichia coli (APEC), Klebsiella pneumoniae carbapenemase (KPC), multidrug-resistant Pseudomonas aeruginosa, and multidrug-resistant Staphylococcus aureus (MRSA) in the PIC assay. Of the supernatants analyzed, some presented synergism for more than one species of multidrug-resistant bacteria. Nine had a synergistic effect with ampicillin on E. coli (APEC) or S. aureus (MRSA), 5 with penicillin G on E. coli (APEC) or KPC, and 3 with vancomycin on KPC.

Conclusion
In summary, the results indicate that supernatants produced from microorganisms can synthesize different classes of molecules with potent antibiotic activity against multiresistant bacteria. Thus, suggesting the use of these microorganisms for use clinical tests to isolate the molecules produced and their potential for use.
Aspartic protease inhibitor enhances resistance to potato virus Y and A in transgenic potato plants
Authors: Osmani Zhila , Sabet Mohammad Sadegh , Nakahara Kenji S. 
Published: May 2022

Abstract
Background
Viruses are the major threat to commercial potato (Solanum tuberosum) production worldwide. Because viral genomes only encode a small number of proteins, all stages of viral infection rely on interactions between viral proteins and host factors. Previously, we presented a list of the most important candidate genes involved in potato plants’ defense response to viruses that are significantly activated in resistant cultivars. Isolated from this list, Aspartic Protease Inhibitor 5 (API5) is a critical host regulatory component of plant defense responses against pathogens. The purpose of this study is to determine the role of StAPI5 in defense of potato against potato virus Y and potato virus A, as well as its ability to confer virus resistance in a transgenic susceptible cultivar of potato (Desiree). Potato plants were transformed with Agrobacterium tumefaciens via a construct encoding the potato StAPI5 gene under the control of the Cauliflower mosaic virus (CaMV) 35S promoter.

Results
Transgenic plants overexpressing StAPI5 exhibited comparable virus resistance to non-transgenic control plants, indicating that StAPI5 functions in gene regulation during virus resistance. The endogenous StAPI5 and CaMV 35S promoter regions shared nine transcription factor binding sites. Additionally, the net photosynthetic rate, stomatal conductivity, and maximum photochemical efficiency of photosystem II were significantly higher in virus-infected transgenic plants than in wild-type plants.

Conclusion
Overall, these findings indicate that StAPI5 may be a viable candidate gene for engineering plant disease resistance to viruses that inhibit disease development.
Erector spinae plane block vs interscalene brachial plexus block for postoperative analgesia management in patients who underwent shoulder arthroscopy
Authors: Kapukaya Furkan , Ekinci Mursel , Ciftci Bahadir , Atalay Yunus Oktay , Gölboyu Birzat Emre , Kuyucu Ersin , Demiraran Yavuz 
Published: May 2022

Abstract
Background
Interscalene brachial plexus block (ISB) is the gold standard method used for postoperative analgesia after arthroscopic shoulder surgery. Ultrasound guided erector spinae plane block (ESPB) is an interfascial plane block. The aim of this study is to compare the analgesic efficacy of ESPB and ISB after shoulder arthroscopy. The primary outcome is the comparison of the perioperative and postoperative opioid consumptions.

Methods
Sixty patients with ASA score I-II planned for arthroscopic shoulder surgery were included in the study. ESPB was planned in Group ESPB (n = 30), and ISB was planned in Group ISB (n = 30). Intravenous fentanyl patient-controlled analgesia was administered to both groups in the postoperative period. Intraoperative and postoperative opioid and analgesic consumption of both groups, side effects and complications related to opioid use, postoperative pain scores and rescue analgesic use were recorded in the first 48 h postoperatively.

Results
Pain scores were significantly higher in the ESPB group in the first 4 h postoperatively than in the ISB group (p < 0.05). The total fentanyl consumption and number of patients using rescue analgesics in the postoperative period were significantly higher in the ESPB group (p < 0.05). The incidence of nausea in the postoperative period was significantly higher in the ESPB group (p < 0.05).

Conclusions
In our study, it was seen that ISB provided more effective analgesia management compared to ESPB in patients underwent shoulder arthroscopy surgery.
Nanomolar EP4 receptor potency and expression of eicosanoid-related enzymes in normal appearing colonic mucosa from patients with colorectal neoplasia
Authors: Feddersen Ulrike Ries , Hendel Sebastian Kjærgaard , Berner-Hansen Mark Alexander , Jepps Thomas Andrew , Berner-Hansen Mark , Bindslev Niels 
Published: May 2022

Abstract
Background
Aberrations in cyclooxygenase and lipoxygenase (LOX) pathways in non-neoplastic, normal appearing mucosa from patients with colorectal neoplasia (CRN), could hypothetically qualify as predisposing CRN-markers.

Methods
To test this hypothesis, biopsies were obtained during colonoscopy from macroscopically normal colonic mucosa from patients with and without CRN. Prostaglandin E2 (PGE2) receptors, EP1-4, were examined in Ussing-chambers by exposing biopsies to selective EP receptor agonists, antagonists and PGE2. Furthermore, mRNA expression of EP receptors, prostanoid synthases and LOX enzymes were evaluated with qPCR.

Results
Data suggest that PGE2 binds to both high and low affinity EP receptors. In particular, PGE2 demonstrated EP4 receptor potency in the low nanomolar range. Similar results were detected using EP2 and EP4 agonists. In CRN patients, mRNA-levels were higher for EP1 and EP2 receptors and for enzymes prostaglandin-I synthase, 5-LOX, 12-LOX and 15-LOX.

Conclusions
In conclusion, normal appearing colonic mucosa from CRN patients demonstrates deviating expression in eicosanoid pathways, which might indicate a likely predisposition for early CRN development and furthermore that PGE2 potently activates high affinity EP4 receptor subtypes, supporting relevance of testing EP4 antagonists in colorectal neoplasia management.
Trajectories and determinants of emergency department use among nursing home residents: a time series analysis (2012–2019)
Authors: Giacomini Gianmarco , Minutiello Ettore , Politano Gianfranco , Dalmasso Marco , Albanesi Beatrice , Campagna Sara , Gianino Maria Michela 
Published: May 2022

Abstract
Background
Emergency department (ED) use among nursing home (NH) residents is an internationally-shared issue that is understudied in Italy. The long term care in Italy is part of the health system. This study aimed to assess trajectories of ED use among NH residents and determinants between demographic, health supply, clinical/functional factors.

Methods
A pooled, cross-sectional, time series analysis was performed in an Italian region in 2012/2019. The analysis measured the trend of ED user percentages associated with chronic conditions identified at NH admission. A GLM multivariate model was used to evaluate determinants of ED use. The variables collected were sex, age, assistance intensity, destination after discharge from NH, chronic conditions at NH admission, need for daily life assistance, degree of mobility, cognitive impairments, behavioural disturbances and were taken from two databases of the official Italian National Information System (FAR and C2 registries) that were combined to create a unique and anonymous code for each patient.

Results
A total of 37,311 residents were enrolled; 55.75% (20,800 residents) had at least one ED visit. The majority of the residents had cardiovascular (25.99%) or mental diseases (24.37%). In all pathologies, the percentage of ED users decreased and the decrease accelerated over time. These results were confirmed in the fixed effects regression model (coefficient for linear term (b = − 3.6177, p = 0, 95% CI = [− 5.124, − 2.1114]); coefficient for quadratic term = − 0.7691, p = 0.0046, 95% CI = [− 1.2953, − 0.2429]). Analysis showed an increased odds of ED visits involving males (OR = 1.27, 95% CI 1.24;1.30) and patients affected by urogenital diseases (OR = 1.16, 95% CI [1.031–1.314]). The lowest odds of ED visits were observed among subjects aged > 90 years (OR = 0.64, 95% CI [0.60–0.67]), who required assistance for their daily life activities (OR = 0.86; 95% CI = [0.82, 0.91]), or with serious cognitive disturbances (OR = 0.86; 95% CI = [0.84, 0.89]), immobile (OR = 0.93; 95% CI = [0.89, 0.96]), or without behavioural disturbances (OR = 0.92; 95% CI = [0.90, 0.94]).

Conclusions
The percentage of ED users has decreased, through support from the Italian disciplinary long-term care system. The demographic, clinical/functional variables associated with ED visits in this study will be helpful to develop targeted and tailored interventions to avoid unnecessary ED use.
Multi-site observational maternal and infant COVID-19 vaccine study (MOMI-vax): a study protocol
Authors: Munoz Flor M. , Beigi Richard H. , Posavad Christine M. , Richardson Barbra A. , Chu Helen Y. , Bok Karin , Campbell James , Cardemil Cristina , DeFranco Emily , Frenck Robert W. , Makhene Mamodikoe , Piper Jeanna M. , Sheffield Jeanne , Miller Ashley , Neuzil Kathleen M. 
Published: May 2022

Abstract
Background
Pregnant women were excluded from investigational trials of COVID-19 vaccines. Limited data are available to inform pregnant and postpartum women on their decisions to receive a COVID-19 vaccine.

Methods
The goal of this observational, prospective cohort study is to evaluate the immunogenicity and safety of various Emergency Use Authorization (EUA) or licensed COVID-19 vaccines administered to pregnant or lactating women and describe the transplacental antibody transfer and kinetics of antibodies in mothers and infants. The study is adaptive, allowing additional groups to be added as new vaccines or vaccine regimens are authorized. Up to 20 clinical research institutions in the United States (U.S.) will be included. Approximately 200 pregnant women and 65 postpartum women will be enrolled per EUA or licensed COVID-19 vaccine formulation in the U.S. This study will include pregnant and postpartum women of all ages with and without chronic medical conditions. Their infants will be enrolled and followed beginning at birth in the pregnant cohort and beginning at the earliest possible time point in the postpartum cohort. Blood samples will be collected for immunogenicity outcomes and pregnancy and birth outcomes assessed among women and infants. Primary analyses will be descriptive and done by vaccine type and/or platform.

Discussion
Given the long-standing and legitimate challenges of enrolling pregnant individuals into clinical trials early in the vaccine development pipeline, this study protocol describes our current study and provides a template to inform the collection of data for pregnant individuals receiving COVID-19 or other vaccines.

Trial registration
NCT05031468.
Characteristics of fetal physiological and pathological uterine effusion observed on prenatal ultrasonography: a case report
Authors: Wang Lei , Chen Lizhu , Li Dongmei , Wang Bing , Yang Zeyu 
Published: May 2022

Abstract
Background
The prenatal detection rate of fetal uterine effusion is very low, and current case reports mainly focus on pathological hydrometrocolpos. We presented two cases of fetal physiological uterine effusion with different ultrasonic characteristics and compared them with one case of hydrometrocolpos with the hope of identifying strategies to reduce misdiagnosis of fetal uterine effusion.

Case presentation
This paper reports the cases of two female fetuses with abnormal pelvic echoes in the third trimester, referred to a tertiary center to be screened for suspected pelvic teratoma and cystic mass, respectively. Ultrasound consultation revealed fetal uterine effusion. The two fetuses were delivered at our hospital after a full term. Re-examining the uterus and adnexa of the neonates revealed that the uterine effusion had subsided naturally. Another female fetus had a large cystic mass in the pelvic cavity in the third trimester, and prenatal examination indicated fetal hydrometrocolpos. The fetus was delivered at our hospital after a full term. The hydrometrocolpos existed even after birth. After consultation with a neonatal surgeon and gynecologist, the newborn was diagnosed with congenital imperforate hymen with hydrometrocolpos. Hymen puncture and open drainage led to a good prognosis.

Conclusions
Prenatal ultrasonography plays an important role in diagnosing and differentiating between physiological and pathological fetal uterine effusion. It can help reduce misdiagnoses that can lead to incorrect clinical decisions.
Utilization of radiation therapy and predictors of noncompliance among Syrian refugees in Turkey
Authors: Sayan Mutlay , Eren Mehmet Fuat , Kilic Sarah Sabrine , Kotek Ayse , Kaplan Sedenay Oskeroglu , Duran Ozge , Cukurcayır Funda , Babalıoglu Ibrahim , Or Ozlem Derinalp , Ozturk Gul Aysen , Eroglu Celalettin , Teke Fatma , Kurtul Neslihan , Kutuk Tugce , Bicakci Beyhan Ceylaner , Senyurek Sukran , Aktan Meryem , Mamidanna Swati , Ohri Nisha , Haffty Bruce , Atalar Banu 
Published: May 2022

Abstract
Background
Access to cancer care is a problem that continues to plague refugees displaced from their home countries. The turbulent political crisis in Syria, which has led to millions of refugees seeking asylum in Turkey, merits further attention. We aimed to study the rate of utilization of radiation therapy among Syrian refugees with cancer living in Turkey in an attempt to identify the contributing factors predictive of non-compliance with prescribed RT.

Methods
In this retrospective review of 14 institutional databases, Syrian refugee patients in Turkey with a cancer diagnosis from January 2015 to December 2019 who were treated with RT were identified. The demographic data, treatment compliance rates, and toxicity outcomes in these patients were surveyed. Variable predictors of noncompliance such as age, sex, diagnosis, treatment length, and toxicity were studied. The association between these variables and patient noncompliance was determined.

Results
We identified 10,537 patients who were diagnosed with cancer during the study period, of whom 1010 (9.6%) patients were treated with RT. Breast cancer (30%) and lung cancer (14%) were the most common diagnoses with up to 68% of patients diagnosed at an advanced stage (Stage III, IV). 20% of the patients were deemed noncompliant. Treatment with concurrent chemoradiotherapy (OR 1.61, 95% CI 1.06–2.46, p = 0.023) and living in a refugee camp (OR 3.62, 95% CI 2.43–5.19, p < 0.001) were associated with noncompliance. Age, sex and treatment length were not significantly associated with noncompliance.

Conclusions
Noncompliance with radiotherapy among Syrian refugees in Turkey remains an area of concern with a multitude of factors contributing to these alarming numbers. Further studies to better ascertain the finer nuances of this intricately complex problem and a global combination of efforts can pave the way to providing a solution.
GECOP-MMC: phase IV randomized clinical trial to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mytomicin-C after complete surgical cytoreduction in patients with colon cancer peritoneal metastases
Authors: Pereira Fernando , Serrano Angel , Manzanedo Israel , Pérez-Viejo Estibalitz , González-Moreno Santiago , González-Bayón Luis , Arjona-Sánchez Alvaro , Torres Juan , Ramos Isabel , Barrios Maria E. , Cascales Pedro , Morales Rafael , Boldó Enrique , García-Fadrique Alfonso , Arteaga Xabier , Gutierrez-Calvo Alberto , Sánchez-García Susana , Asensio Enrique , Ramírez Cesar P. , Artiles Manuel , Vaqué Javier , Parra Pedro A. , Villarejo Pedro , Muñoz-Casares Cristóbal , Turienzo Estrella , Calero Alicia , Torrejimeno Isabel Jaén , Prieto Isabel , Galindo Julio , Borrego Vicente , Marcello Manuel E. , Rihuete Cristina , Carrasco Joaquin , Gomez-Quiles Luis 
Published: May 2022

Abstract
Background
The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m2 (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m2) is the preferred regime to evaluate in future clinical studies.

Methods
GECOP-MMC is a prospective, open-label, randomized, multicenter phase IV clinical trial that aims to evaluate the effectiveness of HIPEC with high-dose mytomicin-C in preventing the development of peritoneal recurrence in patients with limited peritoneal metastasis from colon cancer (not rectal), after complete surgical cytoreduction. This study will be performed in 31 Spanish HIPEC centres, starting in March 2022. Additional international recruiting centres are under consideration. Two hundred sixteen patients with PCI ≤ 20, in which complete cytoreduction (CCS 0) has been obtained, will be randomized intraoperatively to arm 1 (with HIPEC) or arm 2 (without HIPEC). We will stratified randomization by surgical PCI (1–10; 11–15; 16–20). Patients in both arms will be treated with personalized systemic chemotherapy. Primary endpoint is peritoneal recurrence-free survival at 3 years. An ancillary study will evaluate the correlation between surgical and pathological PCI, comparing their respective prognostic values.

Discussion
HIPEC with high-dose mytomicin-C, in patients with limited (PCI ≤ 20) and completely resected (CCS 0) peritoneal metastases, is assumed to reduce the expected risk of peritoneal recurrence from 50 to 30% at 3 years.

Trial registration
EudraCT number: 2019–004679-37; Clinicaltrials.gov: NCT05250648 (registration date 02/22/2022, ).
Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR)
Authors: Dos Santos Mélanie , Lequesne Justine , Leconte Alexandra , Corbinais Stéphane , Parzy Aurélie , Guilloit Jean-Marc , Varatharajah Sharmini , Brachet Pierre-Emmanuel , Dorbeau Marine , Vaur Dominique , Weiswald Louis-Bastien , Poulain Laurent , Le Gallic Corentin , Castera-Tellier Marie , Galais Marie-Pierre , Clarisse Bénédicte 
Published: May 2022

Abstract
Background
Perioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen is considered as the new standard chemotherapy regimen for perioperative strategy, despite associated with a 5-year overall survival rate (OS) amounting 45% following radical surgery.
Immunotherapy with antibodies that inhibit PD-1/ PD-L1 interaction has recently emerged as a new treatment option with promising and encouraging early trial results for patients with advanced or metastatic gastric or GEJ adenocarcinoma. Currently, no trials have investigated the impact of perioperative immunotherapy in combination with chemotherapy for resectable gastric or GEJ adenocarcinoma.

Methods
GASPAR trial is a multicenter open-label, nonrandomized, phase II trial to evaluate the efficacy and safety of Spartalizumab in combination with the FLOT regimen as perioperative treatment for resectable gastric or GEJ adenocarcinoma. The main endpoint is the proportion of patients with pathological complete regression (pCR) in the primary tumour after preoperative treatment.
Systemic treatment will include a pre-operative neoadjuvant and a post-operative adjuvant treatment, during which FLOT regimen will be administered every two weeks for 4 cycles and Spartalizumab every four weeks for 2 cycles.
For patients with confirmed tumor resectability on imaging assessment, surgery will be realized within 4–6 weeks after the last dose of preoperative chemotherapy. Post-operative systemic treatment will then be initiated within 4–10 weeks after surgery.
Using a Simon’s two-stage design, up to 67 patients will be enrolled, including 23 in the first stage.

Discussion
Currently, no trials have investigated the impact of immunotherapy in combination with FLOT chemotherapy as perioperative treatment for resectable gastric or GEJ adenocarcinoma. Some studies have suggested a change in the tumor immune micro-environment following neoadjuvant chemotherapy in this setting, reinforcing the relevance to propose a phase II trial evaluating efficacy and safety of Spartalizumab in combination with perioperative chemotherapy, with the aim of improving treatment efficacy and survival outcomes.

Trial registration
NCT04736485, registered February, 3, 2021.