bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of oxygen and oxidative stress on de novo acquisition of antibiotic resistance in E. coli and Lactobacillus lactis
Authors: Qi Wenxi , Jonker Martijs J. , Teichmann Lisa , Wortel Meike , ter Kuile Benno H. 
Published: October 2023

Abstract
Background
Bacteria can acquire resistance through DNA mutations in response to exposure to sub-lethal concentrations of antibiotics. According to the radical-based theory, reactive oxygen species (ROS), a byproduct of the respiratory pathway, and oxidative stress caused by reactive metabolic byproducts, play a role in cell death as secondary killing mechanism. In this study we address the question whether ROS also affects development of resistance, in the conditions that the cells is not killed by the antibiotic.

Results
To investigate whether oxygen and ROS affect de novo acquisition of antibiotic resistance, evolution of resistance due to exposure to non-lethal levels of antimicrobials was compared in E. coli wildtype and ΔoxyR strains under aerobic and anaerobic conditions. Since Lactococcus lactis (L. lactis) does not have an active electron transport chain (ETC) even in the presence of oxygen, and thus forms much less ROS, resistance development in L. lactis was used to distinguish between oxygen and ROS. The resistance acquisition in E. coli wildtype under aerobic and anaerobic conditions did not differ much. However, the aerobically grown ΔoxyR strain gained resistance faster than the wildtype or anaerobic ΔoxyR. Inducing an ETC by adding heme increased the rate at which L. lactis acquired resistance. Whole genome sequencing identified specific mutations involved in the acquisition of resistance. These mutations were specific for each antibiotic. The lexA mutation in ΔoxyR strain under aerobic conditions indicated that the SOS response was involved in resistance acquisition.

Conclusions
The concept of hormesis can explain the beneficial effects of low levels of ROS and reactive metabolic byproducts, while high levels are lethal. DNA repair and mutagenesis may therefore expedite development of resistance. Taken together, the results suggest that oxygen as such barely affects resistance development. Nevertheless, non-lethal levels of ROS stimulate de novo acquisition of antibiotic resistance.
Dexmedetomidine modulates neuronal activity of horizontal limbs of diagonal band via α2 adrenergic receptor in mice
Authors: Zhang Xia-wei , Chen Lei , Chen Chang-feng , Cheng Juan , Zhang Ping-ping , Wang Lie-cheng 
Published: October 2023

Abstract
Background and objectives
Dexmedetomidine (DEX) is widely used in clinical sedation which has little effect on cardiopulmonary inhibition, however the mechanism remains to be elucidated. The basal forebrain (BF) is a key nucleus that controls sleep-wake cycle. The horizontal limbs of diagonal bundle (HDB) is one subregions of the BF. The purpose of this study was to examine whether the possible mechanism of DEX is through the α2 adrenergic receptor of BF (HDB).

Methods
In this study, we investigated the effects of DEX on the BF (HDB) by using whole cell patch clamp recordings. The threshold stimulus intensity, the inter-spike-intervals (ISIs) and the frequency of action potential firing in the BF (HDB) neurons were recorded by application of DEX (2 µM) and co-application of a α2 adrenergic receptor antagonist phentolamine (PHEN) (10 µM).

Results
DEX (2 µM) increased the threshold stimulus intensity, inhibited the frequency of action potential firing and enlarged the inter-spike-interval (ISI) in the BF (HDB) neurons. These effects were reversed by co-application of PHEN (10 µM).

Conclusion
Taken together, our findings revealed DEX decreased the discharge activity of BF (HDB) neuron via α2 adrenergic receptors.
Selective optogenetic modulation of the PBN terminals in the lateral hypothalamic area and basal forebrain regulates emergence from isoflurane anesthesia in mice
Authors: Lu Kai , Wang Zhenhuan , Bai Ning , Zhao Ziyu , Zhao Xinrong , He Yun 
Published: October 2023

AbstractWhile the mechanism of general anesthesia has been extensively studied, the underlying neural circuitry has yet to be fully understood. The parabrachial nucleus (PBN) plays a crucial role in modulating wakefulness and promoting arousal from general anesthesia. However, the specific role of PBN projections in the process of general anesthesia remains unclear. In this study, we bilaterally injected AAV-associated viruses encoding excitatory or inhibitory optogenetic probes into the PBN and implanted optical fibers in the LH or BF area. After four weeks, we optogenetically activated or inhibited the PBN-LH and PBN-BF pathways under 1.5 vol% isoflurane. We calculated the time it took for anesthesia induction and emergence, simultaneously monitoring changes in the burst-suppression ratio using electroencephalogram recording. Our findings indicate that optogenetic activation of the PBN-LH and PBN-BF projections plays a significant role in promoting both cortical and behavioral emergence from isoflurane inhalation, without significantly affecting the induction time. Conversely, photoinhibition of these pathways prolonged the recovery time, with no notable difference observed during the induction phase.In summary, our results demonstrate that the PBN-LH and PBN-BF pathways are crucial for promoting arousal from isoflurane general anesthesia, but do not have a pronounced impact on the induction phase.
Learning from the covid-19 outbreaks in long-term care facilities: a systematic review
Authors: Henriques Helga Rafael , Sousa Diana , Faria José , Pinto Joana , Costa Andreia , Henriques Maria Adriana , Durão Maria Cândida 
Published: October 2023

Abstract
Background
The COVID-19 pandemic has devastatingly affected Long-Term Care Facilities (LTCF), exposing aging people, staff members, and visitors. The world has learned through the pandemic and lessons can be taken to adopt effective measures to deal with COVID-19 outbreaks in LTCF. We aimed to systematically review the available evidence on the effect of measures to minimize the risk of transmission of COVID-19 in LTCs during outbreaks since 2021.

Methods
The search method was guided by the preferred reporting items for systematic reviews (PRISMA) and the reporting guideline synthesis without meta-analysis (SWiM) in systematic reviews. The search was performed in April 2023. Observational and interventional studies from the databases of PubMed, Web of Science, Scopus, Cochrane Systematic Reviews, CINAHL, and Academic Search were systematically reviewed. We included studies conducted in the LTCF with outbreaks that quantitatively assess the effect of non-pharmacological measures on cases of COVID-19. Two review authors independently reviewed titles for inclusion, extracted data, and undertook the risk of bias according to pre-specified criteria. The quality of studies was analyzed using the Joanna Briggs Institute Critical Appraisal.

Results
Thirteen studies were included, with 8442 LTCF experiencing COVID-19 outbreaks and 598 thousand participants (residents and staff members). Prevention and control of COVID-19 infection interventions were grouped into three themes: strategic, tactical, and operational measures. The strategic measures reveal the importance of COVID-19 prevention and control as LTCF structural characteristics, namely the LTCF size, new admissions, infection control surveillance, and architectural structure. At the tactical level, the lack of personal and long staff shifts is related to COVID-19's spread. Operational measures with a favorable effect on preventing COVID-19 transmission are sufficient. Personal protective equipment stock, correct mask use, signaling, social distancing, and resident cohorting.

Conclusions
Operational, tactical, and strategic approaches may have a favorable effect on preventing the spread of COVID-19 in LTCFs experiencing outbreaks. Given the heterogeneous nature of the measures, performing a meta-analysis was not possible. Future research should use more robust study designs to explore similar infection control measures in LTCFs during endemic situations with comparable outbreaks.

Trial registration
The protocol of this systematic review was registered in PROSPERO (CRD42020214566).
Diagnosis and treatment of “chronic Lyme”: primum non nocere
Authors: Sébastien Prat , Jacques Dalbin , Catherine Plotton , Xavier Gocko 
Published: October 2023

Abstract
Background
Approximately 10% of patients experience prolonged symptoms after Lyme disease. PTLDS (post treatment Lyme disease syndrome) is a controversial topic. It has been described as a source of overdiagnosis and off-label treatment. This review aims to describe the diagnostic errors and adverse events associated with the diagnosis and treatment of PTLDS.

Methods
systematic review of the literature in the Medline and Cochrane Library databases, according to PRISMA criteria, including randomized clinical trials (RCT), observational studies, and case reports addressing diagnostic errors and adverse events published between January 2010 and November 2020 in English or French. Selection used a quadruple reading process on the basis of the titles and abstracts of the different articles, followed by a full reading.

Results
17 studies were included: 1 RCT, 6 observational studies and 10 case reports. In the 6 observational studies, overdiagnosis rates were very high, ranging from 80 to 100%. The new diagnoses were often psychiatric, rheumatological and neurological. Disorders with somatic symptoms were often cited. Diagnostic delays were identified for cancers and frontoparietal dementia. In the RCT and observational studies, prolonged anti-infective treatments were also responsible for adverse events, with emergency room visits and/or hospitalization. The most common adverse events were diarrhea, sometimes with Clostridium difficile colitis, electrolyte abnormalities, sepsis, bacterial and fungal infections, and anaphylactic reactions.

Conclusion
This review highlights the risks of prolonged anti-infective treatments that have not been proven to be beneficial in PTLDS. It emphasizes the ethical imperative of the “primum non nocere” principle, which underscores the importance of not causing harm to patients. Physicians should exercise caution in diagnosing PTLDS and consider the potential risks associated with off-label treatments.
Radiomics analysis based on CT for the prediction of pulmonary metastases in ewing sarcoma
Authors: Liu Ying , Yin Ping , Cui Jingjing , Sun Chao , Chen Lei , Hong Nan , Li Zhentao 
Published: October 2023

Abstract
Objectives
This study aimed to develop and validate radiomics models on the basis of computed tomography (CT) and clinical features for the prediction of pulmonary metastases (MT) in patients with Ewing sarcoma (ES) within 2 years after diagnosis.

Materials and methods
A total of 143 patients with a histopathological diagnosis of ES were enrolled in this study (114 in the training cohort and 29 in the validation cohort). The regions of interest (ROIs) were handcrafted along the boundary of each tumor on the CT and CT-enhanced (CTE) images, and radiomic features were extracted. Six different models were built, including three radiomics models (CT, CTE and ComB models) and three clinical-radiomics models (CT_clinical, CTE_clinical and ComB_clinical models). The area under the receiver operating characteristic curve (AUC), and accuracy were calculated to evaluate the different models, and DeLong test was used to compare the AUCs of the models.

Results
Among the clinical risk factors, the therapeutic method had significant differences between the MT and non-MT groups (P＜0.01). The six models performed well in predicting pulmonary metastases in patients with ES, and the ComB model (AUC: 0.866/0.852 in training/validation cohort) achieved the highest AUC among the six models. However, no statistically significant difference was observed between the AUC of the models.

Conclusions
In patients with ES, clinical-radiomics model created using radiomics signature and clinical features provided favorable ability and accuracy for pulmonary metastases prediction.
Idiopathic multicentric castleman’s disease mimicking immunoglobulin G4-related disease responding well to Bortezomib: a case report
Authors: Peng Qian , Wu Fan , Shi Yuting , Wang Juan , Zhai Zhimin , Wang Zhitao 
Published: October 2023

Abstract
Background
Castleman’s disease (CD) is a rare disease that has clinical and pathological similarities to lymphoma and is characterized by a high frequency of associated immunological dysfunction. ImmunoglobulinG4-related disease (IgG4-RD) is a collection of systemic disorders that affect numerous organs and are also referred to as IgG4-associated sclerosing diseases. CD and IgG4-RD are difficult to separate because they may manifest similar commin clinical features.

Case presentation
This case describes a 53-year-old female who, during routine medical check-up, exhibited a progressive increase in serum globulin levels and a simultaneous worsening of anemia symptoms, raising concern for a clonal plasma cell disease such as myeloma. However, bone marrow punctures did not reveal any abnormal plasma cells. Also, serum and urine immunofixation electrophoresis demonstrated no abnormal monoclonal protein bands. In addition, several laboratory findings excluded chronic liver disease, chronic infections caused by bacteria or viruses. Later, we found elevated serum IgG4 levels (10,700 mg/L), and identified multiple enlarged lymph nodes throughout the patient’s body. Axillary lymph node aspiration revealed no abnormal lymphocytes, ruling out the possibility of lymphoma. Pathological morphology of the axillary lymph revealed a large number of plasma cells in the lymphatic follicles. In addition, there was a reduction in lymphatic follicle size and apoptosis of the germinal centres. Immunohistochemistry revealed IgG4+/IgG + in > 40% of cells, and more than 100 IgG4 + cells per high powered field (HPF) of specimen. As of now, finding strongly suggested IgG4-RD. This patient was treated with glucocorticoids and various immunosuppressive drugs, such as prednisone, cyclosporine, methotrexate, cyclophosphamide, mycophenolate mofetil, azathioprine and hydroxychloroquine. Unfortunately, the patient did not recover. Ultimately, idiopathic multicentric Castleman disease (iMCD) was diagnosed in relation to the patient’s clinical presentation and laboratory tests, and after combination chemotherapy (VCD: Bortezomib, Cyclophosphamide and Dexamethasone), durable remission was achieved without serious adverse effects. During the follow-up period of one year and ten months, the patient remained stable.

Conclusion
The diagnosis of Castleman must be distinguished from other disorders such as IgG4-RD, malignant lymphoma, reactive hyperplasia of various lymph nodes (mostly caused by viral infections), plasmacytoma, advanced HIV and rheumatic diseases. Besides observing systemic symptoms, laboratory tests such as immunoglobulin levels, complement levels, interleukin levels, and C-reactive protein levels should also be performed in order to determine a diagnosis.
GBP2 is a prognostic biomarker and associated with immunotherapeutic responses in gastric cancer
Authors: Wang Yunfei , Pan Jiadong , An Fangmei , Chen Ke , Chen Jiawei , Nie He , Zhu Yanping , Qian Zhengtao , Zhan Qiang 
Published: October 2023

Abstract
Background
The interferon-induced protein known as guanylate-binding protein 2 (GBP2) has been linked to multiple different cancer types as an oncogenic gene. Although the role of GBP2 in cancer has been preliminarily explored, it is unclear how this protein interacts with tumor immunity in gastric cancer.

Methods
The expression, prognostic value, immune-correlations of GBP2 in gastric cancer was explored in multiple public and in-house cohorts. In addition, the pan-cancer analysis was performed to investigate the immunological role of GBP2 based on The Cancer Genome Atlas (TCGA) dataset, and the predictive value of GBP2 for immunotherapy was also examined in multiple public cohorts.

Results
GBP2 was highly expressed in tumor tissues and associated with poor prognosis in gastric cancer. In addition, GBP2 was associated with the immune-hot phenotype. To be more specific, GBP2 was positively related to immuno-modulators, tumor-infiltrating immune cells (TIICs), immunotherapy biomarkers, and even well immunotherapeutic response. In addition to gastric cancer, GBP2 was expected to be an indicator of high immunogenicity in most cancer types. Importantly, GBP2 could predict the immunotherapeutic responses in at least four different cancer types, including melanoma, urothelial carcinoma, non-small cell lung cancer, and breast cancer.

Conclusions
To sum up, GBP2 expression is a promising pan-cancer biomarker for estimating the immunological characteristics of tumors and may be utilized to detect immuno-hot tumors in gastric cancer.
EDOF intraocular lens design: shift in image plane vs object vergence
Authors: Omidi Pooria , Cayless Alan , Langenbucher Achim 
Published: October 2023

Abstract
Background
To compare 2 different design scenarios of EDOF-IOLs inserted in the Liou-Brennan schematic model eye using raytracing simulation as a function of pupil size.

Methods
Two EDOF IOL designs were created and optimized for the Liou-Brennan schematic model eye using Zemax ray tracing software. Each lens was optimized to achieve a maximum Strehl ratio for intermediate and far vision. In the first scenario, the object was located at infinity (O1), and the image plane was positioned at far focus (I1) and intermediate focus (I2) to emulate far and intermediate distance vision, respectively. In the second scenario, the image plane was fixed at I1 according to the first scenario. The object plane was set to infinity (O1) for far-distance vision and then shifted closer to the eye (O2) to reproduce the corresponding intermediate vision. The performance of both IOLs was simulated for the following 3 test conditions as a function of pupil size: a) O1 to I1, b) O1 to I2, and c) O2 to I1. To evaluate the imaging performance, we used the Strehl ratio, the root-mean-square (rms) of the spot radius, and the spherical aberration of the wavefront for various pupil sizes.

Results
Evaluating the imaging performance of the IOLs shows that the imaging performance of the IOLs is essentially identical for object/image at O1/I1. Designed IOLs perform dissimilarly to each other in near-vision scenarios, and the simulations confirm that there is a slight difference in their optical performance.

Conclusion
Our simulation study recommends considering the difference between object shift and image plane shift in design and test conditions to achieve more accurate pseudoaccommodation after cataract surgery.
Medication-free mental health treatment: a focus group study of milieu therapeutic settings
Authors: Beyene Lise Saestad , Hem Marit Helene , Strand Elin Bolle 
Published: October 2023

Abstract
Background
Medication-free treatment within mental health care aims to offer therapeutic support as an alternative to psychotropic medication. Introducing milieu therapy for severely mentally ill persons in a medication-free unit requires significant changes to the traditional medication-based psychiatric setting. The present study examines how milieu therapists experience working with medication-free treatment for people with severe mental health challenges. The research question was “What may be required to succeed with medication-free treatment in milieu therapeutic settings?”

Methods
A qualitative study with four focus groups were conducted with 23 milieu therapists from three inpatient units in two mental health institutions. Thematic analysis was performed.

Results
One main theme was identified: medication-free treatment involves therapists and patients working together on holistic and personal health promotion. This common thread links the four themes: helping patients to make changes in their life; having time to focus on the individual patient; being a professional companion; and working together as a team with the patient.

Conclusions
A holistic approach is necessary for medication-free treatment to succeed. This requires working together in multidisciplinary teams with a focus on the individual patient. Milieu therapists must engage and take more responsibility in the patient’s process of health promotion. A change from a medical to a humanistic paradigm within mental health care is needed.
Mental Health Information Reporting Assistant (MHIRA)—an open-source software facilitating evidence-based assessment for clinical services
Authors: Zimmermann Ronan , Konjufca Jon , Sakejo Peter , Kilonzo Mrema , Quevedo Yamil , Blum Kathrin , Biba Edison , Mosha Tumaini , Cottin Marianne , Hernández Cristóbal , Kaaya Sylvia , Arenliu Aliriza , Behn Alex 
Published: October 2023

AbstractEvidence-based assessment (EBA) in mental health is a critical aspect of improving patient outcomes and addressing the gaps in mental health care. EBA involves the use of psychometric instruments to gather data that can inform clinical decision-making, inform policymakers, and serve as a basis for research and quality management. Despite its potential, EBA is often hindered by barriers such as workload and cost, leading to its underutilization. Regarding low- and middle-income countries (LMIC), the implementation of EBA is recognized as a key strategy to address and close the prevalent mental health treatment gap.To simplify the application of EBA including in LMIC, an international team of researchers and practitioners from Tanzania, Kosovo, Chile, and Switzerland developed the Mental Health Information Reporting Assistant (MHIRA). MHIRA is an open-source electronic health record that streamlines EBA by digitising psychometric instruments and organising patient data in a user-friendly manner. It provides immediate and convenient reports to inform clinical decision-making.The current article provides a comprehensive overview of the features and technical details of MHIRA, as well as insights from four implementation scenarios. The experience gained during the implementations as well as the user-feedback suggests that MHIRA has the potential to be successfully implemented in a variety of clinical contexts and simplify the use of EBA. However, further research is necessary to establish its potential to sustainably transform healthcare services and impact patient outcomes.In conclusion, MHIRA represents an important step in promoting the widespread adoption of EBA in mental health. It offers a promising solution to the barriers that have limited the use of EBA in the past and holds the potential to improve patient outcomes and support the ongoing efforts to address gaps in mental health care.