bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory entrainment related reverse triggering in mechanically ventilated children
Authors: Blokpoel Robert G.T. , Brandsema Ruben B.R. , Koopman Alette A. , van Dijk Jefta , Kneyber Martin C.J. 
Published: March 2024

Abstract
Background
The underlying pathophysiological pathways how reverse triggering is being caused are not fully understood. Respiratory entrainment may be one of these mechanisms, but both terms are used interchangeably. We sought to characterize reverse triggering and the relationship with respiratory entrainment among mechanically ventilated children with and without acute lung injury.

Methods
We performed a secondary phyiology analysis of two previously published data sets of invasively mechanically ventilated children < 18 years with and without lung injury mechanically ventilated in a continuous or intermittent mandatory ventilation mode. Ventilator waveforms, electrical activity of the diaphragm measured with surface electromyography and oesophageal tracings were analyzed for entrained and non-entrained reverse triggered breaths.

Results
In total 102 measurements (3110 min) from 67 patients (median age 4.9 [1.8 ; 19,1] months) were analyzed. Entrained RT was identified in 12 (12%) and non-entrained RT in 39 (38%) recordings. Breathing variability for entrained RT breaths was lower compared to non-entrained RT breaths. We did not observe breath stacking during entrained RT. Double triggering often occurred during non-entrained RT and led to an increased tidal volume. Patients with respiratory entrainment related RT had a shorter duration of MV and length of PICU stay.

Conclusions
Reverse triggering is not one entity but a clinical spectrum with different mechanisms and consequences.

Trial registration
Not applicable.
rs822336 binding to C/EBPβ and NFIC modulates induction of PD-L1 expression and predicts anti-PD-1/PD-L1 therapy in advanced NSCLC
Authors: Polcaro Giovanna , Liguori Luigi , Manzo Valentina , Chianese Annalisa , Donadio Giuliana , Caputo Alessandro , Scognamiglio Giosuè , Dell’Annunziata Federica , Langella Maddalena , Corbi Graziamaria , Ottaiano Alessandro , Cascella Marco , Perri Francesco , De Marco Margot , Col Jessica Dal , Nassa Giovanni , Giurato Giorgio , Zeppa Pio , Filippelli Amelia , Franci Gianluigi , Piaz Fabrizio Dal , Conti Valeria , Pepe Stefano , Sabbatino Francesco 
Published: March 2024

AbstractEfficient predictive biomarkers are needed for immune checkpoint inhibitor (ICI)-based immunotherapy in non-small cell lung cancer (NSCLC). Testing the predictive value of single nucleotide polymorphisms (SNPs) in programmed cell death 1 (PD-1) or its ligand 1 (PD-L1) has shown contrasting results. Here, we aim to validate the predictive value of PD-L1 SNPs in advanced NSCLC patients treated with ICIs as well as to define the molecular mechanisms underlying the role of the identified SNP candidate. rs822336 efficiently predicted response to anti-PD-1/PD-L1 immunotherapy in advanced non-oncogene addicted NSCLC patients as compared to rs2282055 and rs4143815. rs822336 mapped to the promoter/enhancer region of PD-L1, differentially affecting the induction of PD-L1 expression in human NSCLC cell lines as well as their susceptibility to HLA class I antigen matched PBMCs incubated with anti-PD-1 monoclonal antibody nivolumab. The induction of PD-L1 expression by rs822336 was mediated by a competitive allele-specificity binding of two identified transcription factors: C/EBPβ and NFIC. As a result, silencing of C/EBPβ and NFIC differentially regulated the induction of PD-L1 expression in human NSCLC cell lines carrying different rs822336 genotypes. Analysis by binding microarray further validated the competitive allele-specificity binding of C/EBPβ and NFIC to PD-L1 promoter/enhancer region based on rs822336 genotype in human NSCLC cell lines. These findings have high clinical relevance since identify rs822336 and induction of PD-L1 expression as novel biomarkers for predicting anti-PD-1/PD-L1-based immunotherapy in advanced NSCLC patients.
Risk factors for Toxoplasma gondii infection in dogs: a serological survey
Authors: Dini Filippo Maria , Stancampiano Laura , Poglayen Giovanni , Galuppi Roberta 
Published: March 2024

Abstract
Background
Dogs, as well as a wide variety of other warm-blooded animals, act as intermediate host of Toxoplasma gondii. In dogs, most cases of toxoplasmosis are subclinical, although clinical disease has been sporadically reported. Beyond its role in diagnostic pathways, seropositivity also functions as a reflection of the parasite’s spread within the dog’s living environment. The aim of the present study was to evaluate the possible risk factor associated with seropositivity to T. gondii in dogs in Central-Northern Italy, analysing 120 dogs sera for the presence of IgG antibodies by indirect fluorescence antibody test (IFAT).

Results
The population examined was composed of 54.2% hunting dogs, 24.2% companion dogs, 14.2% truffle dogs and 7.5% watchdogs. Thirty-four (29.2%) dogs tested positive for T. gondii IgG, with titres ranging from 1:40 to 1:1280. Seroprevalence and antibodies titres were not related to dog gender, age or function. The logistic regression and ordered logistic regression results indicated that seroprevalence, and antibody titres were significantly higher in dogs cohabiting with cats, exhibiting coprophagy habits, and living constantly outdoors. Notably, the lifestyle factor showed the highest odds-ratios in the study: dogs living constantly outdoors were found to be at approximately 5 times greater risk of testing positive and having higher antibody titres compared to dogs living both indoors and outdoors.

Conclusion
Both logistic and ordered logistic regression results support the key role of living with cats, engaging in coprophagy behaviours, and maintaining an outdoor lifestyle in increasing the risk of T. gondii infection in dogs. These identified risk factors collectively suggest that both ingesting oocysts, as observed through cat cohabitation and coprophagy, and engaging in predatory behaviours, as possible for outdoor living dogs, are indicating likely sources of T. gondii infection in this host species.
Clinical and economic burden of respiratory syncytial virus in children aged 0–5 years in Italy
Authors: Dovizio Melania , Veronesi Chiara , Bartolini Fausto , Cavaliere Arturo , Grego Stefano , Pagliaro Romina , Procacci Cataldo , Ubertazzo Loredana , Bertizzolo Lorenzo , Muzii Barbara , Parisi Salvatore , Perrone Valentina , Baraldi Eugenio , Bozzola Elena , Mosca Fabio , Esposti Luca Degli 
Published: March 2024

Abstract
Background
Respiratory syncytial virus (RSV) is among the leading causes of hospitalization due to lower respiratory tract infections (LRTIs) in children younger than 5 years worldwide and the second cause of infant death after malaria. RSV infection occurs in almost all the infants before the second year of life with variable clinical severity, often requiring medical assistance. This analysis investigated patients aged 0–5 years with RSV infection focusing on epidemiology, clinical features, and economic burden of RSV-associated hospitalizations in a setting of Italian real clinical practice.

Methods
An observational retrospective analysis was conducted on administrative databases of healthcare entities covering around 2.6 million residents of whom 120,000 health-assisted infants aged < 5 years. From 2010 to 2018, pediatric patients were included in the presence of hospitalization discharge diagnosis for RSV infections, and RSV-related acute bronchiolitis or pneumonia. Epidemiology, demographics, clinical picture and costs were evaluated in RSV-infected patients, overall and stratified by age ranges (0–1, 1–2, 2–5 years) and compared with an age-matched general population.

Results
Overall 1378 RSV-infected children aged 0–5 years were included. Among them, the annual incidence rate of RSV-related hospitalizations was 175–195/100,000 people, with a peak in neonates aged < 1 year (689–806/100,000). While nearly 85% of infected infants were healthy, the remaining 15% presented previous hospitalization for known RSV risk factors, like preterm birth, or congenital heart, lung, and immune diseases. The economic analysis revealed that direct healthcare costs per patient/year were markedly higher in RSV patients than in the general population (3605€ vs 344€).

Conclusions
These findings derived from the real clinical practice in Italy confirmed that RSV has an important epidemiological, clinical, and economic burden among children aged 0–5 years. While the complex management of at-risk infants was confirmed, our data also highlighted the significant impact of RSV infection in infants born at term or otherwise healthy, demonstrating that all infants need protection against RSV disease, reducing then the risk of medium and long-term complications, such as wheezing and asthma.
Navigating uncharted territory with a borrowed map: lessons from setting up the BATH-OUT-2 randomised controlled trial in adult social care and housing services in English local authorities
Authors: McAnuff Jennifer , Rapley Tim , Rooney Leigh , Whitehead Phillip 
Published: March 2024

AbstractPopulations around the world are rapidly ageing and more people are living with multiple long-term conditions. There is an urgent need for evidence about high quality, cost-effective, and integrated systems of health and social care. Health research funders are now also prioritising research in adult social care and wider local authority settings, e.g. housing services.Developing the evidence base for adult social care should include implementing randomised controlled trials, where appropriate. Within the UK, the clinical trial is the established road map for evaluating interventions in the National Health Service (NHS). However, adult social care and local authorities are relatively uncharted territory for trials. BATH-OUT-2 is one of the first clinical trials currently underway within adult social care and housing adaptations services in six English local authorities. It provides an opportunity to explore how the clinical trial road map fares in these settings.Whilst setting up BATH-OUT-2, we encountered challenges with securing funding for the trial, lack of non-NHS intervention costs, using research and support costs as intended, gaining approvals, identifying additional trial sites, and including people who lack the mental capacity to provide informed consent. Overall, our experience has been like navigating uncharted territory with a borrowed map. In the UK, the clinical trial road map was developed for medical settings. Its key features are integrated within the NHS landscape but have been largely absent, unfamiliar, inaccessible, or irrelevant in social care and wider local authority terrain. Navigating the set-up of a clinical trial outside the NHS has been a complicated and disorientating journey.BATH-OUT-2 highlights how local authorities generally and adult social care specifically are a relatively new and certainly different type of setting for trials. Whilst this poses a challenge for conducting trials, it also presents an opportunity to question longstanding assumptions within trials practices, reimagine the conventional clinical trial road map, and take it in new directions. As the UK research landscape moves forward and becomes better primed for randomised evaluations in local authorities, we propose several suggestions for building on recent progress and advancing trials within adult social care and across health and care systems.
Prospective virtual screening combined with bio-molecular simulation enabled identification of new inhibitors for the KRAS drug target
Authors: Ajmal Amar , Alkhatabi Hind A , Alreemi Roaa M. , Alamri Mubarak A. , Khalid Asaad , Abdalla Ashraf N. , Alotaibi Bader S. , Wadood Abdul 
Published: March 2024

AbstractLung cancer is a disease with a high mortality rate and it is the number one cause of cancer death globally. Approximately 12–14% of non-small cell lung cancers are caused by mutations in KRASG12C. The KRASG12C is one of the most prevalent mutants in lung cancer patients. KRAS was first considered undruggable. The sotorasib and adagrasib are the recently approved drugs that selectively target KRASG12C, and offer new treatment approaches to enhance patient outcomes however drug resistance frequently arises. Drug development is a challenging, expensive, and time-consuming process. Recently, machine-learning-based virtual screening are used for the development of new drugs. In this study, we performed machine-learning-based virtual screening followed by molecular docking, all atoms molecular dynamics simulation, and binding energy calculations for the identifications of new inhibitors against the KRASG12C mutant. In this study, four machine learning models including, random forest, k-nearest neighbors, Gaussian naïve Bayes, and support vector machine were used. By using an external dataset and 5-fold cross-validation, the developed models were validated. Among all the models the performance of the random forest (RF) model was best on the train/test dataset and external dataset. The random forest model was further used for the virtual screening of the ZINC15 database, in-house database, Pakistani phytochemicals, and South African Natural Products database. A total of 100 ns MD simulation was performed for the four best docking score complexes as well as the standard compound in complex with KRASG12C. Furthermore, the top four hits revealed greater stability and greater binding affinities for KRASG12C compared to the standard drug. These new hits have the potential to inhibit KRASG12C and may help to prevent KRAS-associated lung cancer. All the datasets used in this study can be freely available at (https://github.com/Amar-Ajmal/Datasets-for-KRAS).
Molecular characterization and zoonotic potential of Cryptosporidium spp. and Giardia duodenalis in humans and domestic animals in Heilongjiang Province, China
Authors: Hao Yaru , Liu Aiqin , Li He , Zhao Yiyang , Yao Lan , Yang Bo , Zhang Weizhe , Yang Fengkun 
Published: March 2024

AbstractBackgroundCryptosporidiosis and giardiasis are significant parasitic diseases shared between humans and domestic animals. Due to the close contact between humans and domestic animals in rural areas, it is important to consider the potential transmission of zoonotic parasites from infected domestic animals to humans. This investigation aimed to determine the prevalence and molecular characteristics ofCryptosporidiumspp. andGiardia duodenalisin domestic animals and villagers.MethodsA total of 116 fecal samples from villagers and 686 fecal samples from domestic animals in Heilongjiang Province, China, were analyzed for two parasites using nested polymerase chain reaction (PCR) targeting various genetic loci and DNA sequence analysis of the PCR products.ResultsBy sequence analysis of theSSUrRNA gene, the prevalence ofCryptosporidiumin humans was 0.9% (1/116), with one species ofC. parvum(n = 1) detected; among domestic animals, the prevalence was 2.6% (18/686), with five species identified:C. suis(n = 7) andC. scrofarum(n = 7) in pigs,C. meleagridis(n = 1) in chickens,C. andersoni(n = 1) in cattle, andC. canis(n = 2) in foxes.C. parvum and C. caniswere further subtyped as IIdA19G1 and XXa4 on the basis ofgp60gene. RegardingG. duodenalis, based on theSSUrRNA,bg,gdh, andtpigenes, the prevalence in domestic animals was 5.1% (31/608), with three assemblages identified: A (n = 1) in pigs, D (n = 1) in foxes, and E (n = 27) in geese, cattle, pigs, ducks, and sheep, along with mixed infection of A + E (n = 1) in one pig and B + E (n = 1) in one sheep. NoG. duodenaliswas detected in humans (0/116).ConclusionsThe present results show that no overlap of subtypes between animals and villagers was found inCryptosporidiumspp. andG. duodenalis, indicating a minor role of domestic animals in infecting humans in this population. However, the presence of zoonotic protozoa in domestic animals highlights the need for special attention to high-risk individuals during close contact with domestic animals.Graphical Abstract
Head and neck cancer of unknown primary: unveiling primary tumor sites through machine learning on DNA methylation profiles
Authors: Stark Leonhard , Kasajima Atsuko , Stögbauer Fabian , Schmidl Benedikt , Rinecker Jakob , Holzmann Katharina , Färber Sarah , Pfarr Nicole , Steiger Katja , Wollenberg Barbara , Ruland Jürgen , Winter Christof , Wirth Markus 
Published: March 2024

Abstract
Background
The unknown tissue of origin in head and neck cancer of unknown primary (hnCUP) leads to invasive diagnostic procedures and unspecific and potentially inefficient treatment options for patients. The most common histologic subtype, squamous cell carcinoma, can stem from various tumor primary sites, including the oral cavity, oropharynx, larynx, head and neck skin, lungs, and esophagus. DNA methylation profiles are highly tissue-specific and have been successfully used to classify tissue origin. We therefore developed a support vector machine (SVM) classifier trained with publicly available DNA methylation profiles of commonly cervically metastasizing squamous cell carcinomas (n = 1103) in order to identify the primary tissue of origin of our own cohort of squamous cell hnCUP patient’s samples (n = 28). Methylation analysis was performed with Infinium MethylationEPIC v1.0 BeadChip by Illumina.

Results
The SVM algorithm achieved the highest overall accuracy of tested classifiers, with 87%. Squamous cell hnCUP samples on DNA methylation level resembled squamous cell carcinomas commonly metastasizing into cervical lymph nodes. The most frequently predicted cancer localization was the oral cavity in 11 cases (39%), followed by the oropharynx and larynx (both 7, 25%), skin (2, 7%), and esophagus (1, 4%). These frequencies concord with the expected distribution of lymph node metastases in epidemiological studies.

Conclusions
On DNA methylation level, hnCUP is comparable to primary tumor tissue cancer types that commonly metastasize to cervical lymph nodes. Our SVM-based classifier can accurately predict these cancers’ tissues of origin and could significantly reduce the invasiveness of hnCUP diagnostics and enable a more precise therapy after clinical validation.
A rare variant of mullerian agenesis: a case report and review of the literature
Authors: Tayade Shriya Devendra , Mehdi Nadia , Dube Rajani , Bose Vaishnavi , Ameer Ashna , Hakim Zainabsadat Tabatabaei , Wattiez Arnaud 
Published: March 2024

Abstract
Introduction
Menstruation is a developmental milestone and usually marks healthy and normal pubertal changes in females. Menarche refers to the onset of first menstruation in a female. The causes of primary amenorrhea include outflow tract abnormalities, resistant endometrium, primary ovarian insufficiency, and disorders of the hypothalamus, pituitary, or other endocrine glands. A rare variant of mullerian agenesis, which warrants an individualized approach to management, is presented here.

Case report
We present here the case of a 25-year-old Indian female with pain in the lower abdomen and primary amenorrhea. After a thorough history, clinical examination, imaging, and diagnostic laparoscopy, two small uteri, a blind upper half vagina, bilateral polycystic ovaries, and a blind transverse connection between the two uteri—a horseshoe band cervix—were detected, which confirmed the diagnosis of mullerian agenesis. There was evidence of adenomyosis in the mullerian duct element. This is a rare form of Müllerian abnormality with an unusual presentation.

Conclusion
Mullerian agenesis is the most common cause of primary amenorrhea with well-developed secondary sexual characteristics. There are various forms of mullerian agenesis. Most of the cases are managed by a multidisciplinary team. Rare variants warrant an individualized approach to management.
Recurrent severe hypocalcemia following chemotherapy regimen changes in advanced breast cancer: two case reports
Authors: Yanase Yurina , Bando Hiroko , Sato Riko , Matsuo Tomohei , Ueda Aya , Okazaki Mai , Hashimoto Sachie , Iguchi-Manaka Akiko , Hara Hisato 
Published: March 2024

Abstract
Background
As an oncologic emergency related to abnormalities in calcium metabolism, hypercalcemia associated with paraneoplastic syndrome and bone metastases is well known. Meanwhile, the incidence of hypocalcemia is low, except in cases associated with bone-modifying agents used for bone metastases. Hypocalcemia induced by bone-modifying agents typically occurs early after the initial administration, and its incidence can be significantly reduced by preventive administration of calcium and vitamin D3 supplements.

Case report
We report two cases of recurrent severe hypocalcemia occurring during chemotherapy for metastatic breast cancer with multiple bone metastases.
Case 1: A 35-year-old Japanese woman developed metastases in the bone, liver, and ovaries during postoperative endocrine therapy for invasive lobular carcinoma of the breast. She underwent chemotherapy and treatment with denosumab. She experienced recurrent episodes of severe hypocalcemia subsequent to a change in the chemotherapy regimen. Case 2: A 65-year-old Japanese woman encountered multiple bone metastases after postoperative anti-human epidermal growth factor receptor 2 therapy and during endocrine therapy for invasive ductal carcinoma of the breast. She underwent anti-human epidermal growth factor receptor 2 therapy and treatment with denosumab. She experienced recurrent severe hypocalcemia subsequent to a change in the chemotherapy regimen to letrozole + lapatinib, trastuzumab emtansine, and lapatinib + capecitabine.

Conclusions
We observed two cases of recurrent severe hypocalcemia in patients with advanced breast cancer and bone metastases after modifications to their therapy regimens. These cases differed from the typical hypocalcemia induced by bone-modifying agents. It is possible that antitumor drugs affect calcium and bone metabolism associated with bone metastases. While these cases are rare, it is crucial for oncologists to be aware of hypocalcemia not only at the initiation of bone-modifying agents but also throughout the entire antitumor therapy, as hypocalcemia can lead to fatal outcomes.
Strong convergence of split equality variational inequality, variational inclusion, and multiple sets fixed point problems in Hilbert spaces with application
Authors: Batra Charu , Chugh Renu , Kumar Rajeev , Suwais Khaled , Almanasra Sally , Mlaiki Nabil 
Published: March 2024

AbstractThis paper introduces an innovative inertial simultaneous cyclic iterative algorithm designed to address a range of mathematical problems within the realm of split equality variational inequalities. Specifically, the algorithm accommodates finite families of split equality variational inequality problems, infinite families of split equality variational inclusion problems, and multiple-sets split equality fixed point problems involving demicontractive operators in infinite-dimensional Hilbert spaces. The algorithm integrates well-established methods, including the cyclic method, the inertial method, the viscosity approximation method, and the projection method. We establish the strong convergence of this proposed algorithm, demonstrating its applicability in various scenarios and unifying disparate findings from existing literature. Additionally, a numerical example is presented to validate the primary convergence theorem.