bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do surrogates predict patient preferences more accurately after a physician-led discussion about advance directives? A randomized controlled trial
Authors: Martins Catarina Sampaio , Sousa Iva , Barros Cláudia , Pires Alexandra , Castro Luisa , da Costa Santos Cristina , Nunes Rui 
Published: July 2022

AbstractBackgroundCaregivers frequently assume the role of surrogate decision-makers but often are unable to accurately predict patients’ preferences. This trial aims to find if the use of the Advance Directives documents as a communication tool, improves the agreement between patients and caregivers.MethodsThis trial occurred in a palliative care service of a Portuguese hospital center. A prospective, single-blinded, controlled, randomized trial, enrolling patients and caregivers as a dyad was conducted. Participants individually fulfilled an Advance Directive document, in which patients reported their end-of-life preferences and caregivers reported their decisions as patients’ health surrogates. Dyads were randomly assigned to the Intervention or the Control group, in which the physician respectively promoted an open discussion about patients’ Advance Directives or evaluated patients’ clinical condition. Caregivers’ Advance Directives as surrogates were collected one month later. Proportions of agreement and Cohen’s κ were used to access agreement and reliability, respectively, between the dyads.ResultsResults from 58 dyads were analyzed. We observed an improvement in agreement between the caregivers’ answers and the patients’ wishes on two-thirds (8/12) of the answers, in the Intervention group, contrasting to one-quarter (3/12) of the answers, in the Control group, despite statistical significance in differences wasn´t obtained.ConclusionsAlthough not reaching statistical significance, the results suggest that discussions of advance directives with physicians may lead to better prepared surrogates.Trial registrationClinicalTrials.gov IDNCT05090072. Retrospectively registered on 22/10/2021.
Finding their place – general practitioners' experiences with palliative care—a Norwegian qualitative study
Authors: Fasting Anne , Hetlevik Irene , Mjølstad Bente Prytz 
Published: July 2022

Abstract
Background
Modern palliative care focuses on enabling patients to spend their remaining time at home, and dying comfortably at home, for those patients who want it. Compared to many European countries, few die at home in Norway. General practitioners’ (GPs’) involvement in palliative care may increase patients’ time at home and achievements of home death. Norwegian GPs are perceived as missing in this work. The aim of this study is to explore GPs’ experiences in palliative care regarding their involvement in this work, how they define their role, and what they think they realistically can contribute towards palliative patients.

Methods
We performed focus group interviews with GPs, following a semi-structured interview guide. We included four focus groups with a total of 25 GPs. Interviews were recorded and transcribed verbatim. We performed qualitative analysis on these interviews, inspired by interpretative phenomenological analysis.

Results
Strengths of the GP in the provision of palliative care consisted of characteristics of general practice and skills they relied on, such as general medical knowledge, being coordinator of care, and having a personal and longitudinal knowledge of the patient and a family perspective. They generally had positive attitudes but differing views about their formal role, which was described along three positions towards palliative care: the highly involved, the weakly involved, and the uninvolved GP.

Conclusion
GPs have evident strengths that could be important in the provision of palliative care. They rely on general medical knowledge and need specialist support. They had no consensus about their role in palliative care. Multiple factors interact in complex ways to determine how the GPs perceive their role and how involved they are in palliative care. GPs may possess skills and knowledge complementary to the specialized skills of palliative care team physicians. Specialized teams with extensive outreach activities should be aware of the potential they have for both enabling and deskilling GPs.
TrackUSF, a novel tool for automated ultrasonic vocalization analysis, reveals modified calls in a rat model of autism
Authors: Netser Shai , Nahardiya Guy , Weiss-Dicker Gili , Dadush Roei , Goussha Yizhaq , John Shanah Rachel , Taub Mor , Werber Yuval , Sapir Nir , Yovel Yossi , Harony-Nicolas Hala , Buxbaum Joseph D. , Cohen Lior , Crammer Koby , Wagner Shlomo 
Published: July 2022

Abstract
Background
Various mammalian species emit ultrasonic vocalizations (USVs), which reflect their emotional state and mediate social interactions. USVs are usually analyzed by manual or semi-automated methodologies that categorize discrete USVs according to their structure in the frequency-time domains. This laborious analysis hinders the effective use of USVs as a readout for high-throughput analysis of behavioral changes in animals.

Results
Here we present a novel automated open-source tool that utilizes a different approach towards USV analysis, termed TrackUSF. To validate TrackUSF, we analyzed calls from different animal species, namely mice, rats, and bats, recorded in various settings and compared the results with a manual analysis by a trained observer. We found that TrackUSF detected the majority of USVs, with less than 1% of false-positive detections. We then employed TrackUSF to analyze social vocalizations in Shank3-deficient rats, a rat model of autism, and revealed that these vocalizations exhibit a spectrum of deviations from appetitive calls towards aversive calls.

Conclusions
TrackUSF is a simple and easy-to-use system that may be used for a high-throughput comparison of ultrasonic vocalizations between groups of animals of any kind in any setting, with no prior assumptions.
Antagonistic effects of mitochondrial matrix and intermembrane space proteases on yeast aging
Authors: Vega Montserrat , Castillo David , de Cubas Laura , Wang Yirong , Huang Ying , Hidalgo Elena , Cabrera Margarita 
Published: July 2022

AbstractBackgroundIn many organisms, aging is characterized by a loss of mitochondrial homeostasis. Multiple factors such as respiratory metabolism, mitochondrial fusion/fission, or mitophagy have been linked to cell longevity, but the exact impact of each one on the aging process is still unclear.ResultsUsing the deletion mutant collection of the fission yeastSchizosaccharomyces pombe, we have developed a genome-wide screening for mutants with altered chronological lifespan. We have identified four mutants associated with proteolysis at the mitochondria that exhibit opposite effects on longevity. The analysis of the respiratory activity of these mutants revealed a positive correlation between increased respiration rate and prolonged lifespan. We also found that the phenotype of the long-lived protease mutants could not be explained by impaired mitochondrial fusion/fission activities, but it was dependent on mitophagy induction. The anti-aging role of mitophagy was supported by the effect of a mutant defective in degradation of mitochondria, which shortened lifespan of the long-lived mutants.ConclusionsOur characterization of the mitochondrial protease mutants demonstrates that mitophagy sustains the lifespan extension of long-lived mutants displaying a higher respiration potential.
Cutaneous epitheliotropic T-cell lymphoma in a donkey – a case report
Authors: Kondratjeva Jevgenija , Julien Florie , Coutelier Céline , Humeau Louis , Moog Fabien , Combarros Daniel , Fourquaux Isabelle , Pressanti Charline , Delverdier Maxence , Moore Peter F. , Cadiergues Marie Christine 
Published: July 2022

AbstractBackgroundCutaneous epitheliotropic T-cell lymphoma is a malignant tumour of the skin already reported in humans, dogs, cats, horses, and other species, but not previously in donkeys. The standard diagnosis is based on clinical, morphological and immunophenotypic data. Differentiation of malignant versus benign proliferation of lymphocytes is crucial; in ambiguous cases T-cell receptor gamma (TRG) molecular clonality should be tested. In the present paper, we report a case of mycosis fungoides diagnosed in a donkey whose diagnosis was based on clinical, histological and immunohistochemical aspects and a positive TRG clonality test.Case presentationA twenty-five-year-old donkey gelding was referred with a mildly pruritic, generalised and severe exfoliative dermatosis. Otherwise, the animal was clinically healthy, though mildly underweight. Dermatological examination revealed severe generalised alopecic and exfoliative dermatitis, occasionally eroded, with high number of large, thin, greyish scales. All mucocutaneous junctions except the hoofs were affected. Ectoparasites and dermatophytes were ruled out. The complete blood count and blood smear evaluation revealed mild normocytic normochromic anemia. The biochemistry panel showed mild hyperproteinemia with albumin within the normal range. Protein electrophoresis showed moderate polyclonal hypergammaglobulinemia. Histological findings were characterised by interface dermatitis with massive exocytosis in the epidermis of a homogenous population of lymphoid cells showing atypia. Clusters of neoplastic cells were present within the epidermis forming Pautrier “microabscesses”. These findings are consistent with cutaneous epitheliotropic lymphoma. Immunohistochemical staining revealed uniform labelling of the neoplastic cells for CD3, and lack of expression of CD20 (a B cell lineage associated marker). Molecular clonality PCR (PARR) was performed using equine TRG primers; this revealed a clonal rearrangement in a heavy polyclonal background. Transmission electronic microscopy showed multiple lymphocytes with convoluted or cerebriform nuclei.ConclusionsThis case report provides the first evidence of clinical, histopathological, immunophenotypic features, electron microscopy findings and molecular analysis of a cutaneous epitheliotropic T-cell lymphoma (mycosis fungoides) in a donkey. Our observations suggest that cutaneous T-cell lymphoma should be included in the differential diagnoses of exfoliative dermatitis, even those progressing in a chronic pattern and/or with few or no pruritus.
Association of serum 25-hydroxyvitamin D (25(OH)D) levels with the gut microbiota and metabolites in postmenopausal women in China
Authors: Gong Jinhua , He Lina , Zou Qinyuan , Zhao Yangyang , Zhang Bangzhou , Xia Rongmu , Chen Baolong , Cao Man , Gong Wenxiu , Lin Lin , Lin Xiujuan , Wang Guowei , Guo Muyun , He Jianquan , Xiao Chuanxing , Chen Jian 
Published: July 2022

Abstract
Background
Vitamin D insufficiency or deficiency is associated with an altered microbiota in older men. However, the relationship between the gut microbiota and 25-hydroxyvitamin D (25(OH)D) levels remains unknown in postmenopausal women. In this study, fecal microbiota profiles for 88 postmenopausal women in the high 25(OH)D (HVD) group (n = 44) and the low 25(OH)D (LVD) group (n = 44) were determined. An integrated 16S rRNA gene sequencing and liquid chromatography–mass spectrometry (LC–MS)-based metabolomics approach was applied to explore the association of serum 25(OH)D levels with the gut microbiota and fecal metabolic phenotype. Adjustments were made using several statistical models for potential confounding variables identified from the literature.

Results
The results demonstrated that the community diversity estimated by the Observe, Chao1 and ACE indexes was significantly lower in the LVD group than in the HVD group. Additionally, two kinds of characteristic differences in the microflora were analyzed in the HVD group, and ten kinds of characteristic differences in the microflora were analyzed in the LVD group. We observed that some bacteria belonging to the genera Bifidobacterium, Bacillus, F0332 and Gemella, were enriched in the LVD group, as were other genera, including Lachnoclostridium, UC5_1_2E3, Ruminococcus_gnavus_group and un_f_Lachnospiraceae. Christensenellaceae, Eggerthellaceae and Cloacibacillus were enriched in the HVD group. The L-pyroglutamic acid, inosine, and L-homocysteic acid levels were higher in the HVD group and were negatively correlated with the 1,2-benzenedicarboxylic acid and cholic acid metabolic levels.

Conclusions
These observations provide a better understanding of the relationships between serum 25(OH)D levels and the fecal microbiota and metabolites in postmenopausal women.
The primary macrophage chemokine, CCL2, is not necessary after a peripheral nerve injury for macrophage recruitment and activation or for conditioning lesion enhanced peripheral regeneration
Authors: Talsma Aaron D. , Niemi Jon P. , Pachter Joel S. , Zigmond Richard E. 
Published: July 2022

AbstractBackgroundPeripheral nerve injuries stimulate the regenerative capacity of injured neurons through a neuroimmune phenomenon termed the conditioning lesion (CL) response. This response depends on macrophage accumulation in affected dorsal root ganglia (DRGs) and peripheral nerves. The macrophage chemokine CCL2 is upregulated after injury and is allegedly required for stimulating macrophage recruitment and pro-regenerative signaling through its receptor, CCR2. In these tissues, CCL2 is putatively produced by neurons in the DRG and Schwann cells in the distal nerve.MethodsCcl2fl/flmice were crossed with Advillin-Cre, P0-Cre, or both to create conditionalCcl2knockouts (CKOs) in sensory neurons, Schwann cells, or both to hypothetically remove CCL2 and macrophages from DRGs, nerves or both. CCL2 was localized using Ccl2–RFPfl/flmice. CCL2–CCR2 signaling was further examined using globalCcl2KOs andCcr2gfpknock-in/knock-outs. Unilateral sciatic nerve transection was used as the injury model, and at various timepoints, chemokine expression, macrophage accumulation and function, and in vivo regeneration were examined using qPCR, immunohistochemistry, and luxol fast blue staining.ResultsSurprisingly, in all CKOs, DRGCcl2gene expression was decreased, while nerveCcl2was not. CCL2–RFP reporter mice revealed CCL2 expression in several cell types beyond the expected neurons and Schwann cells. Furthermore, macrophage accumulation, myelin clearance, and in vivo regeneration were unaffected in all CKOs, suggesting CCL2 may not be necessary for the CL response. Indeed,Ccl2global knockout mice showed normal macrophage accumulation, myelin clearance, and in vivo regeneration, indicating these responses do not require CCL2. CCR2 ligands,Ccl7andCcl12, were upregulated after nerve injury and perhaps could compensate for the absence ofCcl2. Finally,Ccr2gfpknock-in/knock-out animals were used to differentiate resident and recruited macrophages in the injured tissues. Ccr2gfp/gfpKOs showed a 50% decrease in macrophages in the distal nerve compared to controls with a relative increase in resident macrophages. In the DRG there was a small but insignificant decrease in macrophages.ConclusionsCCL2 is not necessary for macrophage accumulation, myelin clearance, and axon regeneration in the peripheral nervous system. Without CCL2, other CCR2 chemokines, resident macrophage proliferation, and CCR2-independent monocyte recruitment can compensate and allow for normal macrophage accumulation.
Associations of visceral adipose tissue with bone mineral density and fracture: observational and Mendelian randomization studies
Authors: Hu Jianying , Zhao Manying , Lin Chenhao , Sun Zhonghan , Chen Guo-Chong , Mei Zhendong , Zheng Yan 
Published: July 2022

Abstract
Background
The associations between visceral adipose tissue (VAT) and bone mineral density (BMD) or fracture have been controversial and the causality of the associations remains to be assessed. This study aimed to explore the associations of VAT^ (predicted value of VAT mass) with BMD and fracture risk in men and women, and to examine their potential causation by two-sample Mendelian randomization (MR) analyses.

Methods
UK Biobank is a large, population-based prospective cohort study that recruited more than 500,000 participants aged 40–69 in the United Kingdom from 2006 to 2010. In this study, we used a validated and reliable prediction model to estimate the VAT amount of the participants. On this basis, linear and nonlinear multivariable statistical models were used to explore the association of VAT^ with BMD and fracture risk in different groups of sex and BMI. In observational analyses, the multivariable linear regression model and Cox proportional-hazards model were used to assess VAT^ association with BMD and fracture risk, respectively. Inverse variance weighting was used as the main result of MR analysis.

Results
In 190,836 men, an inverted U-shaped association was observed between VAT^ and heel BMD (P for nonlinearity < 0.001), with a turning point of VAT^ = 1.25 kg. Per kg increase in VAT^ was associated with a 0.13 standard deviation (SD) increase in heel BMD (P = 1.5 × 10−16) among men with lower amounts of VAT^, and associated with a 0.05 SD decrease in heel BMD (P = 1.3 × 10−15) among men with higher amounts of VAT^. In 193,592 women, per kg increase in VAT^ was monotonically associated with a 0.16 SD increase in heel BMD (P = 1.2 × 10−136, P for VAT^-sex interaction = 8.4 × 10−51). During a median follow-up of 8.2 years, VAT^ was associated with lower risks of hip fractures in the overall men and women (P for VAT^-sex interaction = 1.9 × 10−4 for total fractures; 1.5 × 10−4 for other fractures). There were significant interactions of VAT^ and BMI on heel BMD and fracture risks in men only (P for VAT^-BMI interaction = 5.9 × 10−31 for heel BMD; 2.7 × 10−4 for total fractures; 5.7 × 10−3 for hip fractures; 6.8 × 10−3 for other fractures). In two-sample MR analyses, evidence of causality was not observed between VAT^ and DXA-derived BMD or fractures.

Conclusions
These novel findings demonstrated gender-dependent associations of VAT^ with BMD and fracture risk, with the association in men being modified by adiposity. Evidence of causality was not observed, suggesting that the observational association of VAT^ with BMD and fracture risk could be the result of confounding.
COVID-19 outbreak in a psychiatric hospital: what makes it worse?
Authors: Zoghbi Marouan , Haddad Chadia , Khansa Wael , Karam Elie , Chamoun Angela , Hachem Dory 
Published: July 2022

Abstract
Background
Psychiatric patients could be at risk of worse outcomes from COVID-19 than the general population. The primary objective of the present study was to describe the symptoms and clinical characteristics of COVID-19 patients living in long-term hospital for mental illness in Lebanon. The secondary objective was to evaluate the factors related to COVID-19 disease severity among these patients.

Methods
A retrospective observational study was conducted from September 2020 to January 2021 at the Psychiatric Hospital of the Cross. The total number of COVID‐19 patients in the infected floors is 410 out of 548. The outcome variable was the severity of COVID-19 illness classified into five categories: asymptomatic, mild, moderate, severe and critically ill.

Results
The rate of infection in the affected floors was 74.81%. Almost half of the patients were asymptomatic (49.3%), 43.4% had hyperthermia and only 28.0% had tachycardia and 25.1% developed hypoxia. The multivariate regression analysis showed that higher temperature (ORa = 6.52), lower saturation (ORa = 0.88), higher BMI (ORa = 1.12), higher CRP (ORa = 1.01), being a female (ORa = 4.59), having diabetes (ORa = 8.11) or COPD (ORa = 10.03) were significantly associated with the increase of the COVID-19 severity.

Conclusions
The current study showed that a high rate of infection from COVID-19 was detected in a psychiatric hospital with the majority having asymptomatic to mild symptoms. Female psychiatric patients, desaturation, increase inflammation and comorbidities such as diabetes and COPD were associated with the severity of COVID‐19 among psychiatric patients. Future studies are needed to better understand the causal relation of the factors with severity and long term effects or sequelae of the disease.
Exposure to polycyclic aromatic hydrocarbons during pregnancy and breast tissue composition in adolescent daughters and their mothers: a prospective cohort study
Authors: Kehm Rebecca D. , Walter E. Jane , Oskar Sabine , White Melissa L. , Tehranifar Parisa , Herbstman Julie B. , Perera Frederica , Lilge Lothar , Miller Rachel L. , Terry Mary Beth 
Published: July 2022

Abstract
Background
Polycyclic aromatic hydrocarbons (PAH), which are found in air pollution, have carcinogenic and endocrine disrupting properties that might increase breast cancer risk. PAH exposure might be particularly detrimental during pregnancy, as this is a time when the breast tissue of both the mother and daughter is undergoing structural and functional changes. In this study, we tested the hypothesis that ambient PAH exposure during pregnancy is associated with breast tissue composition, measured one to two decades later, in adolescent daughters and their mothers.

Methods
We conducted a prospective analysis using data from a New York City cohort of non-Hispanic Black and Hispanic mother–daughter dyads (recruited 1998–2006). During the third trimester of pregnancy, women wore backpacks containing a continuously operating air sampling pump for two consecutive days that measured ambient exposure to eight carcinogenic higher molecular weight nonvolatile PAH compounds (Σ8 PAH) and pyrene. When daughters (n = 186) and mothers (n = 175) reached ages 11–20 and 29–55 years, respectively, optical spectroscopy (OS) was used to evaluate measures of breast tissue composition (BTC) that positively (water content, collagen content, optical index) and negatively (lipid content) correlate with mammographic breast density, a recognized risk factor for breast cancer. Multivariable linear regression was used to evaluate associations between ambient PAH exposure and BTC, overall and by exposure to household tobacco smoke during pregnancy (yes/no). Models were adjusted for race/ethnicity, age, and percent body fat at OS.

Results
No overall associations were found between ambient PAH exposure (Σ8 PAH or pyrene) and BTC, but statistically significant additive interactions between Σ8 PAH and household tobacco smoke exposure were identified for water content and optical index in both daughters and mothers (interaction p values < 0.05). Σ8 PAH exposure was associated with higher water content (βdaughters = 0.42, 95% CI = 0.15–0.68; βmothers = 0.32, 95% CI = 0.05–0.61) and higher optical index (βdaughters = 0.38, 95% CI = 0.12–0.64; βmothers = 0.38, 95% CI = 0.12–0.65) in those exposed to household tobacco smoke during pregnancy; no associations were found in non-smoking households (interaction p values < 0.05).

Conclusions
Exposure to ambient Σ8 PAH and tobacco smoke during pregnancy might interact synergistically to impact BTC in mothers and daughters. If replicated in other cohorts, these findings might have important implications for breast cancer risk across generations.