bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired alveolar macrophage 11β-hydroxysteroid dehydrogenase type 1 reductase activity contributes to increased pulmonary inflammation and mortality in sepsis-related ARDS
Authors: Mahida Rahul Y. , Lax Siân , Bassford Christopher R. , Scott Aaron , Parekh Dhruv , Hardy Rowan S. , Naidu Babu , Matthay Michael A. , Stewart Paul M. , Cooper Mark C. , Perkins Gavin D. , Thickett David R. 
Published: April 2023

BackgroundAcute Respiratory Distress Syndrome (ARDS) is a devastating pulmonary inflammatory disorder, commonly precipitated by sepsis. Glucocorticoids are immunomodulatory steroids that can suppress inflammation. Their anti-inflammatory properties within tissues are influenced by their pre-receptor metabolism and amplification from inactive precursors by 11β-hydroxysteroid dehydrogenase type-1 (HSD-1). We hypothesised that in sepsis-related ARDS, alveolar macrophage (AM) HSD-1 activity and glucocorticoid activation are impaired, and associated with greater inflammatory injury and worse outcomes.MethodsWe analysed broncho-alveolar lavage (BAL) and circulating glucocorticoid levels, AM HSD-1 reductase activity and Receptor for Advanced Glycation End-products (RAGE) levels in two cohorts of critically ill sepsis patients, with and without ARDS. AM HSD-1 reductase activity was also measured in lobectomy patients. We assessed inflammatory injury parameters in models of lung injury and sepsis in HSD-1 knockout (KO) and wild type (WT) mice.ResultsNo difference in serum and BAL cortisol: cortisone ratios are shown between sepsis patients with and without ARDS. Across all sepsis patients, there is no association between BAL cortisol: cortisone ratio and 30-day mortality. However, AM HSD-1 reductase activity is impaired in patients with sepsis-related ARDS, compared to sepsis patients without ARDS and lobectomy patients (0.075 v 0.882 v 0.967 pM/hr/106 AMs, p=0.004). Across all sepsis patients (with and without ARDS), impaired AM HSD-1 reductase activity is associated with defective efferocytosis (r=0.804, p=0.008) and increased 30-day mortality. AM HSD-1 reductase activity negatively correlates with BAL RAGE in sepsis patients with ARDS (r=-0.427, p=0.017). Following intra-tracheal lipopolysaccharide (IT-LPS) injury, HSD-1 KO mice demonstrate increased alveolar neutrophil infiltration, apoptotic neutrophil accumulation, alveolar protein permeability and BAL RAGE concentrations compared to WT mice. Caecal Ligation and Puncture (CLP) injury in HSD-1 KO mice results in greater peritoneal apoptotic neutrophil accumulation compared to WT mice.ConclusionsAM HSD-1 reductase activity does not shape total BAL and serum cortisol: cortisone ratios, however impaired HSD-1 autocrine signalling renders AMs insensitive to the anti-inflammatory effects of local glucocorticoids. This contributes to the decreased efferocytosis, increased BAL RAGE concentrations and mortality seen in sepsis-related ARDS. Upregulation of alveolar HSD-1 activity could restore AM function and improve clinical outcomes in these patients.
Clinical relevance of cell-free DNA quantification and qualification during the first month after lung transplantation
Authors: Pedini Pascal , Coiffard Benjamin , Cherouat Nicem , Casas Sylvia , Fina Frédéric , Boutonnet Audrey , Baudey Jean Baptiste , Aho Printil , Basire Agnes , Simon Sophie , Frassati Coralie , Chiaroni Jacques , Reynaud-Gaubert Martine , Picard Christophe 
Published: April 2023

BackgroundMany studies have reported the relevance of donor-derived cfDNA (dd-cfDNA) after lung transplantation (LTx) to diagnose and monitor acute rejection (AR) or chronic rejection or infection (INF). However, the analysis of cfDNA fragment size has not been studied. The aim of this study was to determine the clinical relevance of dd-cfDNA and cfDNA size profiles in events (AR and INF) during the first month after LTx.MethodsThis prospective, single-center study includes 62 LTx recipients at the Marseille Nord Hospital, France. Total cfDNA quantification was performed by fluorimetry and digital PCR, dd-cfDNA by NGS (AlloSeq cfDNA-CareDX®), and the size profile by BIABooster (Adelis®). A bronchoalveolar lavage and transbronchial biopsies at D30 established the following groups: not-injured and injured graft (AR, INF, or AR+INF).ResultsQuantification of total cfDNA was not correlated with the patient’s status at D30. The percentage of dd-cfDNA was significantly higher for injured graft patients at D30 (p=0.0004). A threshold of 1.72% of dd-cfDNA correctly classified the not-injured graft patients (negative predictive value of 91.4%). Among recipients with dd-cfDNA &gt;1.72%, the quantification of small sizes (80-120bp) &gt;3.70% identified the INF with high performance (specificity and positive predictive value of 100%).ConclusionWith the aim of considering cfDNA as a polyvalent non-invasive biomarker in transplantation, an algorithm combining the quantification of dd-cfDNA and small sizes of DNA may significantly classify the different types of allograft injuries.
Deep-sea freezer
Authors: Kawagucci Shinsuke , Matsui Yohei , Nomaki Hidetaka , Chen Chong 
Published: April 2023

Recovery of samples from the deep ocean in pristine condition is difficult due to large environmental differences between the deep and surface waters through which the samples necessarily must be transported. Here, we propose a concept for deep-sea sample recovery: a deep-sea freezer using thermoelectric cooling capable of generating ice in the deep and recover them frozen on-board ships. As a proof of concept, we present the DSF-α, a prototype Deep-Sea Freezer based on Peltier device rated at 2000 m. In situ assessments of the DSF-α on remotely operated vehicles showed its capacity to reach freezing (-13.0°C) temperatures in the deep, as well as recovering seawater frozen on deck. Although the DSF-α is limited in that achieving sufficient freezing for useful sample recovery is time consuming, the deep-sea freezer opens a whole frontier of new possibilities for preserving various types of deep-sea samples and has the potential to be adapted according to various needs of the deep-sea research community. With the first literal ‘marine snow’ in the deep, we offer a glimpse to a future where the recovery of reliable bathyal samples is no longer laborious.
ARA-net: an attention-aware retinal atrophy segmentation network coping with fundus images
Authors: Chen Lei , Zhou Yuying , Gao Songyang , Li Manyu , Tan Hai , Wan Zhijiang 
Published: April 2023

BackgroundAccurately detecting and segmenting areas of retinal atrophy are paramount for early medical intervention in pathological myopia (PM). However, segmenting retinal atrophic areas based on a two-dimensional (2D) fundus image poses several challenges, such as blurred boundaries, irregular shapes, and size variation. To overcome these challenges, we have proposed an attention-aware retinal atrophy segmentation network (ARA-Net) to segment retinal atrophy areas from the 2D fundus image.MethodsIn particular, the ARA-Net adopts a similar strategy as UNet to perform the area segmentation. Skip self-attention connection (SSA) block, comprising a shortcut and a parallel polarized self-attention (PPSA) block, has been proposed to deal with the challenges of blurred boundaries and irregular shapes of the retinal atrophic region. Further, we have proposed a multi-scale feature flow (MSFF) to challenge the size variation. We have added the flow between the SSA connection blocks, allowing for capturing considerable semantic information to detect retinal atrophy in various area sizes.ResultsThe proposed method has been validated on the Pathological Myopia (PALM) dataset. Experimental results demonstrate that our method yields a high dice coefficient (DICE) of 84.26%, Jaccard index (JAC) of 72.80%, and F1-score of 84.57%, which outperforms other methods significantly.ConclusionOur results have demonstrated that ARA-Net is an effective and efficient approach for retinal atrophic area segmentation in PM.
Communication and information sharing with pediatric patients including refugees with advanced cancer, their caregivers, and health care professionals in Jordan: a qualitative study
Authors: Alarjeh Ghadeer , Boufkhed Sabah , Alrjoub Waleed , Guo Ping , Yurduşen Sema , Ahmed Fahad , Abdal-Rahman Mousa , Alajarmeh Sawsan , Alnassan Anwar , Al-Awady Shireen , Kutluk Tezer , Harding Richard , Shamieh Omar 
Published: April 2023

IntroductionEffective communication in pediatric palliative cancer care is an important aspect of practice to enhance patient- and family-centered care, and to optimize decision-making. However, little is known about communication preferences practices from the perspectives of children, caregivers and their health care professionals (HCPs) in the Middle Eastern region. Furthermore, involving children in research is crucial but limited. This study aimed to describe the communication and information-sharing preferences and practices of children with advanced cancer, their caregivers, and health care professionals in Jordan.MethodsA qualitative cross-sectional study was conducted using semi-structured face to face interviews with three groups of stakeholders (children, caregivers and HCPs). Purposive sampling recruited a diverse sample from inpatient and outpatient settings at a tertiary cancer center in Jordan. Procedures were in line with the Consolidated criteria for reporting qualitative research (COREQ) reporting guidelines. Verbatim transcripts were thematically analyzed.FindingsFifty-two stakeholders participated: 43 Jordanian and 9 refugees (25 children, 15 caregivers and 12 HCPs). Four major themes emerged: 1) Hiding information between the three stakeholders which includes parents who hide the information from their sick children and ask the HCPs to do so to protect the child from distressful emotions and children who hide their suffering from their parents to protect them from being sad; 2) Communication and sharing of clinical versus non-clinical information; 3) Preferred communication styles such as use of a companionate approach by acknowledging patients and caregivers’ suffering, building a trustful relationship, proactive information sharing, considering child age and medical status, parents as facilitators in communication, and patients’ and caregivers’ health literacy; 4) Communication and information sharing with refugees where they had dialect issues, which hindered effective communication. Some refugees had unrealistically high expectations regarding their child’s care and prognosis, which posed challenges to communication with staff.DiscussionThe novel findings of this study should inform better child-centered practices and better engage them in their care decisions. This study has demonstrated children’s ability to engage in primary research and to express preferences, and parents’ ability to share views on this sensitive topic.
Abscopal effect observed in visceral and osseous metastases after liver SBRT in combination with nivolumab and relatlimab for sinonasal mucosal melanoma—a case report
Authors: Cerbon Danielle , Moya-Brown Karen , Mihaylov Ivaylo B. , Spieler Benjamin 
Published: April 2023

BackgroundPrimary sinonasal mucosal melanoma (SNMM) is a rare, aggressive histology usually diagnosed at advanced stages and associated with poor prognosis. Evidence regarding etiology, diagnosis, and treatment mainly derives from case reports, retrospective series, and national databases. In the treatment of metastatic melanoma, anti-CTLA-4 and anti-PD-1 checkpoint blockade increased 5-year overall survival from ~10% (prior to 2011) to ~50% (between 2011 and 2016). In March of 2022, the FDA approved the use of relatlimab, a novel anti-LAG3 immune checkpoint inhibitor, for the treatment of melanoma.Case presentationA 67-year-old woman with locally advanced SNMM underwent debulking surgery, adjuvant RT, and first-line immunotherapy (ImT) with nivolumab but developed local progression. The patient started a second course of ImT with nivolumab and ipilimumab, but this was discontinued after two cycles due to an immune-related adverse event (irAE, hepatitis with elevated liver enzymes). Interval imaging identified visceral and osseous metastases including multiple lesions in the liver and in the lumbar spine. She went on to receive a third course of ImT with nivolumab and the novel agent relatlimab with concurrent stereotactic body radiation therapy (SBRT) to the largest liver tumor only, delivered in five 10-Gy fractions using MRI guidance. A PET/CT performed 3 months after SBRT demonstrated complete metabolic response (CMR) of all disease sites including non-irradiated liver lesions and spinal metastatic sites. After two cycles of the third course of ImT, the patient developed severe immune-related keratoconjunctivitis and ImT was discontinued.ConclusionThis case report describes the first complete abscopal response (AR) in an SNMM histology and the first report of AR following liver SBRT with the use of relatlimab/nivolumab combination ImT for metastatic melanoma in the setting of both visceral and osseous lesions. This report suggests that the combination of SBRT with ImT potentiates the adaptive immune response and is a viable path for immune-mediated tumor rejection. The mechanisms behind this response are hypothesis-generating and remain an area of active research with exceedingly promising potential.
Laparoscopic distal gastrectomy demonstrates acceptable outcomes regarding complications compared to open surgery for gastric cancer patients with pylorus outlet obstruction
Authors: Wang Sen , Zhang Yigang , Chen Zetian , Li Qingya , Li Fengyuan , Li Zheng , Liu Hongda , Xuan Zhe , Xia Yiwen , Xu Penghui , Fang Lang , Wang Linjun , Zhang Diancai , Xu Hao , Yang Li , Xu Zekuan 
Published: April 2023

BackgroundFor gastric cancer (GC) patients with pylorus outlet obstruction (POO), whether laparoscopic surgery has advantages over open surgery remains unclear. This study aims to investigate the differences between patients with and without POO in open and laparoscopic groups and to determine the differences between laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) in GC patients with POO.MethodsA total of 241 GC patients with POO who underwent distal gastrectomy at the Department of Gastric Surgery of the First Affiliated Hospital of Nanjing Medical University between 2016 and 2021 were included in this study. A total of 1,121 non-POO patients who underwent laparoscopic surgery and 948 non-POO patients who underwent open surgery from 2016 to 2021 were also enrolled in the study. We compared complication rates and hospital stays between open and laparoscopic groups.ResultsThere was no significant difference for LDG between GC patients with and without POO regarding the overall complication rates (P = 0.063), the Grade III–V complication rate (P = 0.673), and the anastomotic complication rate (P = 0.497) from 2016 to 2021. The patients with POO had longer preoperative hospital stay (P = 0.001) and postoperative hospital stay (P=0.007) compared to patients without POO. No significant difference was observed for open patients between POO and non-POO patients regarding the overall complication rate (P = 0.357), grade III–V complication rate (P = 1.000), and anastomosis-related complication rate (P = 0.766). Compared with open surgery in GC patients with POO (n = 111), the total complication rate of the LDG group was 16.2%, which was significantly lower than that of the open group (26.1%, P = 0.041). No significant differences in the Grade III–V complication rate (P = 0.574) and anastomotic complication rate (P = 0.587) were observed between laparoscopic and open groups. Patients receiving laparoscopic surgery had shorter postoperative hospital stay than open surgery (P = 0.001). More resected lymph nodes (LNs) were also observed in the laparoscopic group (P = 0.0145).ConclusionThe comorbidity of GC with POO does not increase the complication rate after laparoscopic or open distal gastrectomy. In GC patients with POO, laparoscopic surgery shows advantages over open surgery with a lower overall complication rate, shorter postoperative hospital stay, and more harvested lymph nodes. Laparoscopic surgery is a safe, feasible, and effective treatment for GC with POO.
Relationship between depression, anxiety, stress, and SARS-CoV-2 infection: a longitudinal study
Authors: Ausserhofer Dietmar , Mahlknecht Angelika , Engl Adolf , Piccoliori Giuliano , Pfitscher Gernot , Silbernagl Philipp , Giacomoni Francesca , Pycha Roger , Lombardo Stefano , Gärtner Timon , Mian Michael , Meier Horand , Wiedermann Christian J. , Keim Roland 
Published: April 2023

ObjectivesWe aimed to (1) describe the course of the emotional burden (i.e., depression, anxiety, and stress) in a general population sample during the coronavirus pandemic in 2020 and 2021 and (2) explore the association between emotional burden and a serologically proven infection with SARS-CoV-2.Study designThis longitudinal study involved a sample of community-dwelling persons aged ≥14 years from the general population of South Tyrol (Province of Bolzano-Bozen, Northern Italy). Data were collected at two stages over a 1-year period in 2020 and 2021.MethodsPersons were invited to participate in a survey on socio-demographic, health-related and psychosocial variables (e.g., age, chronic diseases, Depression Anxiety Stress Scale, DASS-21), as well as in the serological testing for of SARS-CoV-2-specific immunoglobulins.ResultsIn 2020, 855 (23.8%) out of 3,600 persons participated; in 2021, 305 (35.7%) out of 855 were tested again. We observed a statistically significant decrease in mean DASS-21 scores for depression, stress, and total scores between 2020 and 2021, yet not for anxiety. Persons with a confirmed SARS-CoV-2-infection between the first and second data collection exhibited increased emotional burden compared to those without SARS-CoV-2-infection. The odds of participants with a self-reported diagnosis of mental disorder for future infection with SARS-CoV-2 was almost four times higher than that of participants without mental disorders (OR:3.75; 95%CI:1.79-7.83).ConclusionOur findings support to the hypothesis of a psycho-neuroendocrine-immune interplay in COVID-19. Further research is necessary to explore the mechanisms underlying the interplay between mental health and SARS-CoV-2 infections.
Incidence and factors associated of early non-response in first-treatment and drug-naïve patients with schizophrenia: a real-world study
Authors: Zhang Lin , Bai Aohan , Tang Zhongyu , Liu Xuebing , Li Yi , Ma Jun 
Published: April 2023

BackgroundSchizophrenia is a severe and persistent mental condition that causes disability. For subsequent clinical care, it is extremely practical to effectively differentiate between patients who respond to therapy quickly and those who do not. This study set out to document the prevalence and risk factors for patient early non-response.MethodsThe current study included 143 individuals with first-treatment and drug-naïve (FTDN) schizophrenia. Patients were classified as early non-responders based on a Positive and Negative Symptom Scale (PANSS) score reduction of less than 20% after 2 weeks of treatment, otherwise as early responders. Clinical subgroups’ differences in demographic data and general clinical data were compared, and variables related to early non-response to therapy were examined.ResultsTwo weeks later, a total of 73 patients were described as early non-responders, with an incidence of 51.05%. The early non-response subgroup had significantly higher PANSS scores, Positive symptom subscale (PSS) scores, General psychopathology subscale (GPS) scores, Clinical global impression scale - severity of illness (CGI-SI) and Fasting blood glucose (FBG) levels compared to the early-response subgroup. CGI-SI and FBG were risk factors for early non-response.ConclusionHigh rates of early non-response have been seen in FTDN schizophrenia patients, and risk variables for predicting early non-response include CGI-SI scores and FBG levels. However, we need more in-depth studies to confirm the generalizable range of these two parameters.
Early-onset Alzheimer’s disease with depression as the first symptom: a case report with literature review
Authors: Liu Meichen , Xie Xueting , Xie Jinghui , Tian Shiyun , Du Xuemei , Feng Hongbo , Zhang Huimin 
Published: April 2023

BackgroundAlzheimer’s disease is a common neurodegenerative disease, and patients with early-onset Alzheimer’s disease (onset age &lt; 65 years) often have atypical symptoms, which are easily misdiagnosed and missed. Multimodality neuroimaging has become an important diagnostic and follow-up method for AD with its non-invasive and quantitative advantages.Case presentationWe report a case of a 59-year-old female with a diagnosis of depression at the age of 50 after a 46-year-old onset and a 9-year follow-up observation, who developed cognitive dysfunction manifested by memory loss and disorientation at the age of 53, and eventually developed dementia. Combined with neuropsychological scales (MMSE and MOCA scores decreased year by year and finally reached the dementia criteria) and the application of multimodal imaging. MRI showed that the hippocampus atrophied year by year and the cerebral cortex was extensively atrophied. 18F-FDG PET image showed hypometabolism in right parietal lobes, bilateral frontal lobes, bilateral joint parieto-temporal areas, and bilateral posterior cingulate glucose metabolism. The 18F-AV45 PET image showed the diagnosis of early-onset Alzheimer’s disease was confirmed by the presence of Aβ deposits in the cerebral cortex.ConclusionEarly-onset Alzheimer’s disease, which starts with depression, often has atypical symptoms and is prone to misdiagnosis. The combination of neuropsychological scales and neuroimaging examinations are good screening tools that can better assist in the early diagnosis of Alzheimer’s disease.Graphical Abstract