bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rupture of an epidural filter connector during bolus administration of local anesthetic: a case report
Authors: Nahrwold Daniel A. , Muncey Aaron R. , Aldawoodi Nasrin N. , Evans Raymond M. , Hoffman Jamie P. 
Published: May 2021

AbstractBackgroundEpidural catheters are routinely placed for many surgical procedures and to treat various pain conditions. Known complications arising from epidural catheter equipment malfunction include epidural pump failure, epidural catheter shearing, epidural catheter connector failure, epidural filter connector cracking, and loss-of-resistance syringe malfunction. Practitioners need to be aware of these potentially dangerous complications and take measures to mitigate the chances of causing significant patient harm. We report on the complete breakage of an epidural filter connector during epidural bolus administration of local anesthetic by hand with a syringe.Case presentationA B. Braun Perifix® epidural catheter was placed in a 73-year-old male scheduled for radical prostatectomy. During the operation, a continuous infusion of local anesthetic was administered through the epidural catheter in addition to general endotracheal anesthesia. At the conclusion of surgery and after extubation, the patient endorsed incisional pain. The epidural filter connector broke in half as a bolus of local anesthetic was administered by hand with a syringe. The local anesthetic sprayed widely throughout the room as the fragmented epidural filter connector became a projectile object that recoiled and struck the patient.ConclusionsThis incident placed the patient and surrounding healthcare providers at substantial risk for injury and infection from the fractured epidural filter connector becoming a projectile object and from the local anesthetic spray. The most plausible cause of this event was from a large amount of pressure being applied to the filter connector. This may have occurred by excessive force being applied by hand to the syringe, by the presence of a clogged filter, or by the catheter being kinked or blocked proximal to the filter. Being aware of this deleterious complication and potentially modifying existing epidural bolus techniques, such as using smaller syringes with less applied force and checking all epidural components vigilantly prior to and during bolus administration, can help anesthesia providers deliver the safest possible care to patients with epidural catheters.
PRimary care rEsponse to domestic violence and abuse in the COvid-19 panDEmic (PRECODE): protocol of a rapid mixed-methods study in the UK
Authors: Szilassy Eszter , Barbosa Estela Capelas , Dixon Sharon , Feder Gene , Griffiths Chris , Johnson Medina , De Simoni Anna , Wileman Vari , Panovska-Griffiths Jasmina , Dowrick Anna 
Published: May 2021

Abstract
Background
The implementation of lockdowns in the UK during the COVID-19 pandemic resulted in a system switch to remote primary care consulting at the same time as the incidence of domestic violence and abuse (DVA) increased. Lockdown-specific barriers to disclosure of DVA reduced the opportunity for DVA detection and referral.
The PRECODE (PRimary care rEsponse to domestic violence and abuse in the COvid-19 panDEmic) study will comprise quantitative analysis of the impact of the pandemic on referrals from IRIS (Identification and Referral to Improve Safety) trained general practices to DVA agencies in the UK and qualitative analysis of the experiences of clinicians responding to patients affected by DVA and adaptations they have made transitioning to remote DVA training and patient support.

Methods/Design
Using a rapid mixed method design, PRECODE will explore and explain the dynamics of DVA referrals and support before and during the pandemic on a national scale using qualitative data and over four years of referrals time series data.
We will undertake interrupted-time series and non-linear regression analysis, including sensitivity analyses, on time series of referrals to DVA services from routinely collected data to evaluate the impact of the pandemic and associated lockdowns on referrals to the IRIS Programme, and analyse key determinants associated with changes in referrals.
We will also conduct an interview- and observation-based qualitative study to understand the variation, relevance and feasibility of primary care responses to DVA before and during the pandemic and its aftermath.
The triangulation of quantitative and qualitative findings using rapid analysis and synthesis will enable the articulation of multiscale trends in primary care responses to DVA and complex mechanisms by which these responses have changed during the pandemic.

Discussion
Our findings will inform the implementation of remote primary care and DVA service responses as services re-configure. Understanding the adaptation of clinical and service responses to DVA during the pandemic is crucial for the development of evidence-based, effective remote support and referral beyond the pandemic.

Trial registration
PRECODE is an observational epidemiologic study, not an intervention evaluation or trial. We will not be reporting results of an intervention on human participants.
Meta-analysis of the effects of smooth endoplasmic reticulum aggregation on birth outcome
Authors: Zhang Hongqin , Hu Wenhui , Zhong Ying , Guo Zhenhua 
Published: May 2021

Abstract
Background
Smooth endoplasmic reticulum aggregation (SERa, SER+) has been reported to increase the risk of birth malformations and other abnormal outcomes, miscarriage, and perinatal complications. Other studies, however, suggest that SER+ embryos may develop into healthy infants. One report indicates that 25% of in vitro fertilization (IVF) centers discard SER+ oocytes. Thus, we investigated the effect of SER+ on birth outcomes in IVF and intracytoplasmic sperm injection.

Methods
We performed a literature search using PubMed, ScienceDirect, Cochrane, Embase, Ovid, and Scopus. We found a total of 1500 relevant studies between 1978 and 2020 and conducted a meta-analysis to study the effects of SER+ on live births, birth weight, and the number of metaphase II (MII) oocytes retrieved per cycle.

Results
Eleven eligible studies were included. If the SER+ zygote was evaluated again at the embryo transfer (ET) stage, SER+ did not affect birth or infant body weight. Stimulated ovaries producing too many oocytes per cycle were positively correlated with SER+ (OR = 1.28, 95% CI = 0.41–2.15; p = 0.004). SER+ was positively correlated with oocyte maturation rate, and observed heterogeneity in a previous meta-analysis was likely due to maternal age. Our data also showed that SER+ cycles produced more oocytes but achieved the same number of births from ET.

Conclusions
The use of SER+ MII oocytes is rare, with the collection of many oocytes in 1 cycle potentially inducing SER+. SER+ may be more common than we originally thought, as some SER+ is found in all oocytes. Although SER+ positively affected oocyte maturation rate, it did not affect births. We hypothesized that this is because the best embryos are chosen at every step of the process, and the oocytes with the poorest characteristics are removed. We therefore suggest a standard method for measuring SER+. Although embryos produced from SER+ cycles can be used, they should only be transferred when no other suitable embryos are available over several cycles.
The role of undergraduate medical students training in respect for patient confidentiality
Authors: Beltran-Aroca Cristina M , Ruiz-Montero Rafael , Labella Fernando , Girela-López Eloy 
Published: May 2021

Abstract
Background
Encouraging professional integrity is vital for providing a standard of excellence in quality medical care and education and in promoting a culture of respect and responsibility. The primary objective of this work consisted of studying the relationship of medical students to the right to patient privacy in Spain, specifically by analysing the conditions for accessing patient clinical histories (CHs).

Methods
A cross-sectional study was conducted based on a questionnaire sent by e-mail to final-year students at 41 Spanish universities. It had 14 multiple choice and closed questions framed in 3 large blocks. The first question addressed basic general knowledge issues on the right to privacy and the obligation for confidentiality. The two remaining blocks were made up of questions directed towards evaluating the frequency with which certain requirements and action steps related to students attending patients were performed and regarding the guarantees associated with accessing and handling patient CHs both on paper and in the Electronic Medical Record.

Results
A total of 245 valid replies were considered. A total of 67.8 % of participants were women, with an average age of 24.05 ± 3.49 years. Up to 90.6 % were aware that confidentiality affected the data in CHs, although 43.3 % possessed non-anonymized photocopies of patient clinical reports outside the healthcare context, and only 49.8 % of the students were always adequately identified. A total of 59.2 % accessed patient CHs on some occasions by using passwords belonging to healthcare professionals, 77.2 % of them did not have the patients’ express consent, and 71.9 % accessed a CH that was not anonymised.

Conclusions
The role of healthcare institutions and universities is considered to be fundamental in implementing educational measures regarding the risks and ethical and legal problems arising from the use of CHs among professionals and students. A thorough study of medical ethics is needed through the analysis of clinical cases and direct exposure to situations in which the patient’s confidentiality is questioned.
Head to head randomized trial of two decision aids for prostate cancer
Authors: Fagerlin Angela , Holmes-Rovner Margaret , Hofer Timothy P. , Rovner David , Alexander Stewart C. , Knight Sara J. , Ling Bruce S. , A.Tulsky James , Wei John T. , Hafez Khaled , Kahn Valerie C. , Connochie Daniel , Gingrich Jeffery , Ubel Peter A. 
Published: May 2021

Abstract
Background
While many studies have tested the impact of a decision aid (DA) compared to not receiving any DA, far fewer have tested how different types of DAs affect key outcomes such as treatment choice, patient–provider communication, or decision process/satisfaction. This study tested the impact of a complex medical oriented DA compared to a more simplistic decision aid designed to encourage shared decision making in men with clinically localized prostate cancer.

Methods
1028 men at 4 VA hospitals were recruited after a scheduled prostate biopsy. Participants completed baseline measures and were randomized to receive either a simple or complex DA. Participants were men with clinically localized cancer (N = 285) by biopsy and who completed a baseline survey. Survey measures: baseline (biopsy); immediately prior to seeing the physician for biopsy results (pre- encounter); one week following the physician visit (post-encounter). Outcome measures included treatment preference and treatment received, knowledge, preference for shared decision making, decision making process, and patients’ use and satisfaction with the DA.

Results
Participants who received the simple DA had greater interest in shared decision making after reading the DA (p = 0.03), found the DA more helpful (p’s < 0.01) and were more likely to be considering watchful waiting (p = 0.03) compared to those receiving the complex DA at Time 2. While these differences were present before patients saw their urologists, there was no difference between groups in the treatment patients received.

Conclusions
The simple DA led to increased desire for shared decision making and for less aggressive treatment. However, these differences disappeared following the physician visit, which appeared to change patients’ treatment preferences.
Trial registration This trial was pre-registered prior to recruitment of participants.
Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer
Authors: Lainé Muriel , Fanning Sean W. , Chang Ya-Fang , Green Bradley , Greene Marianne E. , Komm Barry , Kurleto Justyna D. , Phung Linda , Greene Geoffrey L. 
Published: May 2021

Abstract
Background
Endocrine therapy remains the mainstay of treatment for estrogen receptor-positive (ER+) breast cancer. Constitutively active mutations in the ligand binding domain of ERα render tumors resistant to endocrine agents. Breast cancers with the two most common ERα mutations, Y537S and D538G, have low sensitivity to fulvestrant inhibition, a typical second-line endocrine therapy. Lasofoxifene is a selective estrogen receptor modulator with benefits on bone health and breast cancer prevention potential. This study investigated the anti-tumor activity of lasofoxifene in breast cancer xenografts expressing Y537S and D538G ERα mutants. The combination of lasofoxifene with palbociclib, a CDK4/6 inhibitor, was also evaluated.

Methods
Luciferase-GFP tagged MCF7 cells bearing wild-type, Y537S, or D538G ERα were injected into the mammary ducts of NSG mice (MIND model), which were subsequently treated with lasofoxifene or fulvestrant as single agents or in combination with palbociclib. Tumor growth and metastasis were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements, and histological analysis.

Results
As a monotherapy, lasofoxifene was more effective than fulvestrant at inhibiting primary tumor growth and reducing metastases. Adding palbociclib improved the effectiveness of both lasofoxifene and fulvestrant for tumor suppression and metastasis prevention at four distal sites (lung, liver, bone, and brain), with the combination of lasofoxifene/palbociclib being generally more potent than that of fulvestrant/palbociclib. X-ray crystallography of the ERα ligand binding domain (LBD) shows that lasofoxifene stabilizes an antagonist conformation of both wild-type and Y537S LBD. The ability of lasofoxifene to promote an antagonist conformation of Y537S, combined with its long half-life and bioavailability, likely contributes to the observed potent inhibition of primary tumor growth and metastasis of MCF7 Y537S cells.

Conclusions
We report for the first time the anti-tumor activity of lasofoxifene in mouse models of endocrine therapy-resistant breast cancer. The results demonstrate the potential of using lasofoxifene as an effective therapy for women with advanced or metastatic ER+ breast cancers expressing the most common constitutively active ERα mutations.
Cryopreservation of human cancers conserves tumour heterogeneity for single-cell multi-omics analysis
Authors: Wu Sunny Z. , Roden Daniel L. , Al-Eryani Ghamdan , Bartonicek Nenad , Harvey Kate , Cazet Aurélie S. , Chan Chia-Ling , Junankar Simon , Hui Mun N. , Millar Ewan A. , Beretov Julia , Horvath Lisa , Joshua Anthony M. , Stricker Phillip , Wilmott James S. , Quek Camelia , Long Georgina V. , Scolyer Richard A. , Yeung Bertrand Z. , Segara Davendra , Mak Cindy , Warrier Sanjay , Powell Joseph E. , O’Toole Sandra , Lim Elgene , Swarbrick Alexander 
Published: May 2021

Abstract
Background
High throughput single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for exploring cellular heterogeneity among complex human cancers. scRNA-Seq studies using fresh human surgical tissue are logistically difficult, preclude histopathological triage of samples, and limit the ability to perform batch processing. This hindrance can often introduce technical biases when integrating patient datasets and increase experimental costs. Although tissue preservation methods have been previously explored to address such issues, it is yet to be examined on complex human tissues, such as solid cancers and on high throughput scRNA-Seq platforms.

Methods
Using the Chromium 10X platform, we sequenced a total of ~ 120,000 cells from fresh and cryopreserved replicates across three primary breast cancers, two primary prostate cancers and a cutaneous melanoma. We performed detailed analyses between cells from each condition to assess the effects of cryopreservation on cellular heterogeneity, cell quality, clustering and the identification of gene ontologies. In addition, we performed single-cell immunophenotyping using CITE-Seq on a single breast cancer sample cryopreserved as solid tissue fragments.

Results
Tumour heterogeneity identified from fresh tissues was largely conserved in cryopreserved replicates. We show that sequencing of single cells prepared from cryopreserved tissue fragments or from cryopreserved cell suspensions is comparable to sequenced cells prepared from fresh tissue, with cryopreserved cell suspensions displaying higher correlations with fresh tissue in gene expression. We showed that cryopreservation had minimal impacts on the results of downstream analyses such as biological pathway enrichment. For some tumours, cryopreservation modestly increased cell stress signatures compared to freshly analysed tissue. Further, we demonstrate the advantage of cryopreserving whole-cells for detecting cell-surface proteins using CITE-Seq, which is impossible using other preservation methods such as single nuclei-sequencing.

Conclusions
We show that the viable cryopreservation of human cancers provides high-quality single-cells for multi-omics analysis. Our study guides new experimental designs for tissue biobanking for future clinical single-cell RNA sequencing studies.
Oxidant therapy improves adipogenic differentiation of adipose-derived stem cells in human wound healing
Authors: Ploner Christian , Rauchenwald Tina , Connolly Catherine E. , Joehrer Karin , Rainer Johannes , Seifarth Christof , Hermann Martin , Nagl Markus , Lobenwein Susanne , Wilflingseder Doris , Cappellano Giuseppe , Morandi Evi M. , Pierer Gerhard 
Published: May 2021

Abstract
Background
Adipose-derived stem cells (ASC) and adipocytes are involved in numerous physiological and pathophysiological conditions, which have been extensively described in subcutaneous and visceral fat depots over the past two decades. However, much less is known about ASC and adipocytes outside classical fat tissue depots and their necessity in tissue remodeling after injury. Therefore, we investigated the etiology of adipocytes in human granulation tissue and define their possible role wound healing.

Methods
Identification of human wound tissue adipocytes was determined by immunohistochemical staining of granulation tissue sections from patients undergoing surgical debridement. Stromal cell fractions from granulation tissue and subcutaneous fat tissue were generated by collagenase type II-based protocols. Pro- and anti-inflammatory wound bed conditions were mimicked by THP1- and CD14+ monocyte-derived macrophage models in vitro. Effects of macrophage secretome on ASC differentiation and metabolism were determined by immunoblotting, flow cytometry, and microscopy assessing early and late adipocyte differentiation states. Functional rescuing experiments were conducted by lentiviral transduction of wildtype PPARG, IL1RA, and N-chlorotaurine (NCT) treatment.

Results
Single and clustered adipocyte populations were detected in 11 out of 13 granulation tissue specimens and single-cell suspensions from granulation tissue showed adipogenic differentiation potential. Pro-inflammatory signaling by IFNG/LPS-stimulated macrophages (M (IFNG/LPS)) inhibited the maturation of lipid droplets in differentiated ASC. In contrast, anti-inflammatory IL4/IL13-activated macrophages (M (IL4/IL13)) revealed minor effects on adipocyte development. The M (IFNG/LPS)-induced phenotype was associated with a switch from endogenous fatty acid synthesis to glycolysis-dominated cell metabolism and increased pro-inflammatory cytokine production. Impaired adipogenesis was associated with increased, but seemingly non-functional, CEBPB levels, which failed to induce downstream PPARG and CEBPA. Neither transgenic PPARG overexpression, nor inhibition of IL1B was sufficient to rescue the anti-adipogenic effects induced by IFNG/LPS-activated macrophages. Instead, macrophage co-treatment during stimulation with NCT, a mild oxidant produced by activated granulocytes present in human wounds in vivo, significantly attenuated the anti-adipogenic effects.

Conclusions
In conclusion, the appearance of adipocytes in wound tissue indicates a prevailing anti-inflammatory environment that could be promoted by NCT treatment and may be associated with improved healing outcomes.

Graphical abstract
Non-invasive and minimally invasive glucose monitoring devices: a systematic review and meta-analysis on diagnostic accuracy of hypoglycaemia detection
Authors: Lindner Nicole , Kuwabara Aya , Holt Tim 
Published: May 2021

Abstract
Background
The use of minimally and non-invasive monitoring systems (including continuous glucose monitoring) has increased rapidly over recent years. Up to now, it remains unclear how accurate devices can detect hypoglycaemic episodes. In this systematic review and meta-analysis, we assessed the diagnostic accuracy of minimally and non-invasive hypoglycaemia detection in comparison to capillary or venous blood glucose in patients with type 1 or type 2 diabetes.

Methods
Clinical Trials.gov, Cochrane Library, Embase, PubMed, ProQuest, Scopus and Web of Science were systematically searched. Two authors independently screened the articles, extracted data using a standardised extraction form and assessed methodological quality using a review-tailored quality assessment tool for diagnostic accuracy studies (QUADAS-2). The diagnostic accuracy of hypoglycaemia detection was analysed via meta-analysis using a bivariate random effects model and meta-regression with regard to pre-specified covariates.

Results
We identified 3416 nonduplicate articles. Finally, 15 studies with a total of 733 patients were included. Different thresholds for hypoglycaemia detection ranging from 40 to 100 mg/dl were used. Pooled analysis revealed a mean sensitivity of 69.3% [95% CI: 56.8 to 79.4] and a mean specificity of 93.3% [95% CI: 88.2 to 96.3]. Meta-regression analyses showed a better hypoglycaemia detection in studies indicating a higher overall accuracy, whereas year of publication did not significantly influence diagnostic accuracy. An additional analysis shows the absence of evidence for a better performance of the most recent generation of devices.

Conclusion
Overall, the present data suggest that minimally and non-invasive monitoring systems are not sufficiently accurate for detecting hypoglycaemia in routine use.

Systematic review registration
PROSPERO 2018 CRD42018104812