bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fertility preservation with successful pregnancy outcome in a patient with transplanted heart and non-Hodgkin’s lymphoma – a case report
Authors: Pais Ana Sofia , Guerra Nuno , Couto Daniela , Sousa Ana Paula , Almeida-Santos Teresa 
Published: November 2020

Abstract
Background: Fertility preservation must be discussed with reproductive age women before cancer treatment. Heart transplantation raises complex issues in pregnancy. Pregnancy in a heart transplant woman after pelvic irradiation involves close multidisciplinary follow-up to avoid complications in the mother and the foetus. We report the first live birth in a heart transplant woman after pelvic irradiation, chemotherapy and fertility preservation.
Case presentation: A 36-year-old heart transplant woman with pelvic non-Hodgkin lymphoma spared her fertility, with cryopreservation of oocytes and embryos, before chemotherapy and pelvic irradiation. After multidisciplinary discussion and pre-conception evaluation, pregnancy was achieved. A close follow-up by a multidisciplinary team allowed a normal pregnancy without maternal or foetal complications and the delivery of a healthy infant.

Conclusions
Achieving pregnancy in heart transplant women with iatrogenic ovarian failure after oncologic treatment including pelvic irradiation is possible and can be successful. Careful and close surveillance by a multidisciplinary team is mandatory due to increased risk of maternal and foetal complications.
C-reactive protein- and clinical symptoms-guided strategy in term neonates with early-onset sepsis reduced antibiotic use and hospital stay: a quality improvement initiative
Authors: Gyllensvärd Johan , Ingemansson Fredrik , Hentz Elisabet , Studahl Marie , Elfvin Anders 
Published: November 2020

Abstract
Background
Early-onset sepsis (EOS) is a potentially life-threatening complication of birth. Clinical symptoms are often unspecific and biomarkers have low predictive values for EOS. Therefore, clinical suspicion often leads to antibiotic therapy in neonates with a negative blood culture. In the study we evaluated if a quality improvement initiative could reduce unwarranted antibiotic use in a safe way in term neonates with culture-negative sepsis.

Methods
The quality improvement initiative included new treatment guidelines and were introduced on 11 June 2018. The guidelines included C-reactive protein- and clinical symptoms-guided decision-making and shorter intravenous antibiotic therapy. All term neonates treated for EOS at Ryhov Hospital, Jönköping, Sweden were studied before (period 1: 2016–2017) and after the introduction of the new guidelines (period 2: 11 June 2018 to 30 Sept 2019).
Laboratory and clinical data were analysed.

Results
There were 7618 term neonates in period 1 and 5005 term neonates in period 2. We identified 140 (1.8%) EOS in period 1 and 97 (1.9%) EOS in period 2. During period 1 and 2, there were 61 (61/140, 44%) and 59 (59/97, 61%) EOS neonates, respectively, who met the criteria for shorter antibiotic treatment. The number of positive blood cultures were seven (0.92/1000 live births) and five (1.0/1000 live births) in period 1 and 2. The median C-reactive protein were 52 mg/L (37–62) in period 1 and 42 mg/L (31–56) in period 2 in the group who met the criteria of the guidelines. The duration of antibiotic therapy (Median: seven vs. five days, p < 0.001) and hospital stay (Median: seven vs. five days, p < 0.001) as well as healthcare costs (decreased by €122,000/year) was reduced in the group who met the criteria after the introduction of the guidelines.

Conclusion
C-reactive protein- and clinical symptoms-guided decision-making for EOS significantly decreased the duration of antibiotic therapy and hospital stay, and hence reduced healthcare costs, with no reinfection in a cohort of term infants.

Trial registration
Trial registration number: ISRCTN29535824. Date of registration: 28 May 2020. Retrospectively registered.
Sleep in disorders of consciousness: behavioral and polysomnographic recording
Authors: Mertel Isabella , Pavlov Yuri G. , Barner Christine , Müller Friedemann , Diekelmann Susanne , Kotchoubey Boris 
Published: November 2020

Abstract
Background
Sleep-wakefulness cycles are an essential diagnostic criterion for disorders of consciousness (DOC), differentiating prolonged DOC from coma. Specific sleep features, like the presence of sleep spindles, are an important marker for the prognosis of recovery from DOC. Based on increasing evidence for a link between sleep and neuronal plasticity, understanding sleep in DOC might facilitate the development of novel methods for rehabilitation. Yet, well-controlled studies of sleep in DOC are lacking. Here, we aimed to quantify, on a reliable evaluation basis, the distribution of behavioral and neurophysiological sleep patterns in DOC over a 24-h period while controlling for environmental factors (by recruiting a group of conscious tetraplegic patients who resided in the same hospital).

Methods
We evaluated the distribution of sleep and wakefulness by means of polysomnography (EEG, EOG, EMG) and video recordings in 32 DOC patients (16 unresponsive wakefulness syndrome [UWS], 16 minimally conscious state [MCS]), and 10 clinical control patients with severe tetraplegia. Three independent raters scored the patients’ polysomnographic recordings.

Results
All but one patient (UWS) showed behavioral and electrophysiological signs of sleep. Control and MCS patients spent significantly more time in sleep during the night than during daytime, a pattern that was not evident in UWS. DOC patients (particularly UWS) exhibited less REM sleep than control patients. Forty-four percent of UWS patients and 12% of MCS patients did not have any REM sleep, while all control patients (100%) showed signs of all sleep stages and sleep spindles. Furthermore, no sleep spindles were found in 62% of UWS patients and 21% of MCS patients. In the remaining DOC patients who had spindles, their number and amplitude were significantly lower than in controls.

Conclusions
The distribution of sleep signs in DOC over 24 h differs significantly from the normal sleep-wakefulness pattern. These abnormalities of sleep in DOC are independent of external factors such as severe immobility and hospital environment.
Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies
Authors: Cupp Meghan A. , Cariolou Margarita , Tzoulaki Ioanna , Aune Dagfinn , Evangelou Evangelos , Berlanga-Taylor Antonio J. 
Published: November 2020

Abstract
Background
Although neutrophils have been linked to the progression of cancer, uncertainty exists around their association with cancer outcomes, depending on the site, outcome and treatments considered. We aimed to evaluate the strength and validity of evidence on the association between either the neutrophil to lymphocyte ratio (NLR) or tumour-associated neutrophils (TAN) and cancer prognosis.

Methods
We searched MEDLINE, Embase and Cochrane Database of Systematic Reviews from inception to 29 May 2020 for systematic reviews and meta-analyses of observational studies on neutrophil counts (here NLR or TAN) and specific cancer outcomes related to disease progression or survival. The available evidence was graded as strong, highly suggestive, suggestive, weak or uncertain through the application of pre-set GRADE criteria.

Results
A total of 204 meta-analyses from 86 studies investigating the association between either NLR or TAN and cancer outcomes met the criteria for inclusion. All but one meta-analyses found a hazard ratio (HR) which increased risk (HR > 1). We did not find sufficient meta-analyses to evaluate TAN and cancer outcomes (N = 9). When assessed for magnitude of effect, significance and bias related to heterogeneity and small study effects, 18 (9%) associations between NLR and outcomes in composite cancer endpoints (combined analysis), cancers treated with immunotherapy and some site specific cancers (urinary, nasopharyngeal, gastric, breast, endometrial, soft tissue sarcoma and hepatocellular cancers) were supported by strong evidence.

Conclusion
In total, 60 (29%) meta-analyses presented strong or highly suggestive evidence. Although the NLR and TAN hold clinical promise in their association with poor cancer prognosis, further research is required to provide robust evidence, assess causality and test clinical utility.

Trial registration
PROSPERO CRD42017069131.
Paraoxonase single nucleotide variants show associations with polycystic ovary syndrome: a meta-analysis
Authors: Kunjantarachot Anthicha , Pabalan Noel , Jarjanazi Hamdi , Christofolini Denise Maria , Montagna Erik , Barbosa Caio Parente , Bianco Bianca 
Published: November 2020

AbstractBackgroundEtiology of polycystic ovary syndrome (PCOS) is attributed to genetic and environmental factors. One environmental factor is oxidative stress. Paraoxonase 1 (PON1) is an antioxidant high-density lipoprotein-associated enzyme encoded by thePON1gene. ThePON1gene has been implicated in the risk for PCOS, the influence of which appears to come from single nucleotide variants (SNVs) at multiple genetic loci. However, association study reports have been inconsistent which compels a meta-analysis to obtain more precise estimates.MethodsFrom 12 publications, extracted genotype data were used in two genetic procedures. First, linkage disequilibrium (LD) was used to group eightPONSNVs into three: LD1, LD2 and LD3. Second, frequencies of the variant (var), wild-type (wt) and heterozygous (het) genotypes were used for genetic modeling (allele-genotype for LD1 and standard for LD2 and LD3). Risk associations were expressed in terms of pooled odds ratios (ORs), 95% confidence intervals (CIs) andPa-values. Evidence was considered strong when significance was high (Pa < 0.0001) and heterogeneity absent (I2 = 0%). Pooled effects were subjected to modifier (power), subgroup (Asian/Caucasian), outlier, sensitivity and publication bias treatments. Multiple comparisons were Bonferroni-corrected.ResultsThis meta-analysis generated 11 significant outcomes, five in LD1, six in LD2 and none in LD3. All six LD2 outcomes did not survive the Bonferroni-correction but two of the five in LD1 did. These two core LD1 findings conferred greater odds of PCOS to thevarallele in the highly significant (Pa < 0.0001) overall (OR 1.44, 95% CI 1.24–1.67) and Asian (OR 1.41, 95% CI 1.20–1.65) outcomes. Of these two core outcomes, the Asian effect was homogeneous (I2 = 0%) but not the overall (I2 = 29%).ConclusionsOf the eightPONSNVs examined, two (rs854560 and rs662) were associated with PCOS risk. These 1.4-fold increased risk effects rendered Asians susceptible to PCOS. High statistical power, high significance, zero to low-level heterogeneity, robustness and lack of bias in the core outcomes underpinned the strong evidence for association.
The dark side of the spoon - glucose, ketones and COVID-19: a possible role for ketogenic diet?
Authors: Paoli Antonio , Gorini Stefania , Caprio Massimiliano 
Published: November 2020

AbstractThe novel coronavirus disease (COVID-19) is posing a serious challenge to the health-care systems worldwide, with an enormous impact on health conditions and loss of lives. Notably, obesity and its related comorbidities are strictly related with worse clinical outcomes of COVID-19 disease. Recently, there is a growing interest in the clinical use of ketogenic diets (KDs), particularly in the context of severe obesity with related metabolic complications. KDs have been proven effective for a rapid reduction of fat mass, preserving lean mass and providing an adequate nutritional status. In particular, the physiological increase in plasma levels of ketone bodies exerts important anti-inflammatory and immunomodulating effects, which may reveal as precious tools to prevent infection and potential adverse outcomes of COVID-19 disease. We discuss here the importance of KDs for a rapid reduction of several critical risk factors for COVID-19, such as obesity, type 2 diabetes and hypertension, based on the known effects of ketone bodies on inflammation, immunity, metabolic profile and cardiovascular function. We do believe that a rapid reduction of all modifiable risk factors, especially obesity with its metabolic complications, should be a pillar of public health policies and interventions, in view of future waves of SARS-CoV-2 infection.
Emergence of plasmid-mediated mcr genes from Gram-negative bacteria at the human-animal interface
Authors: Javed Humera , Saleem Sidrah , Zafar Aizza , Ghafoor Aamir , Shahzad Ahmad Bin , Ejaz Hasan , Junaid Kashaf , Jahan Shah 
Published: November 2020

Abstract
Background
The global emergence of plasmid-mediated colistin resistance (Col-R) conferred by mcr genes in gram-negative rods (GNRs) has jeopardized the last treatment option for multidrug-resistant bacterial infections in humans. This study aimed to assess the emergence of mcr gene-mediated Col-R in GNRs isolated from humans and animals in Pakistan.

Methods
Animal and clinical specimens collected from various sources were prospectively analysed using standard microbiological procedures. Pathogens were identified using the API 20E and API 20NE systems (bioMerieux). Minimum inhibitory concentration (MIC) against colistin was determined using the MIC detection methods, and multiplex polymerase chain reaction (PCR) was used to amplify the mcr-1 to mcr-5 genes.

Results

We isolated 126 (88.1%) animal and 17 (11.9%) human Col-R phenotypes, among which there was a significant association (P < 0.01) of Escherichia coli and Proteus mirabilis with animals and of Acinetobacter baumannii with humans. Animal strains exhibited statistically significant (P < 0.05) resistance to co-trimoxazole, chloramphenicol, and moxifloxacin, and the human pathogens exhibited statistically significant (P < 0.05) antibiotic resistance to cephalosporins, carbapenems, and piperacillin-tazobactam. For Col-R strains, MIC50 values were > 6 µg/mL and > 12 µg/mL for human and animal isolates, respectively. mcr genes were detected in 110 (76.9%) bacterial strains, of which 108 (98.2%) were mcr-1 and 2 (1.8%) were mcr-2.

Conclusions
The detection of a considerable number of mcr-1 and mcr-2 genes in animals is worrisome, as they are now being detected in clinical pathogens. The acquisition of mcr genes by colistin-susceptible bacteria could leave us in a post-antibiotic era.
Vaccines to prevent COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING VACCINE Project)
Authors: Korang Steven Kwasi , Juul Sophie , Nielsen Emil Eik , Feinberg Joshua , Siddiqui Faiza , Ong Giok , Klingenberg Sarah , Veroniki Areti Angeliki , Bu Fanlong , Thabane Lehana , Thomsen Allan Randrup , Jakobsen Janus C. , Gluud Christian 
Published: November 2020

AbstractBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19.Methods/designWe will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; “active placebo;” no intervention; standard care; an “active” intervention; another vaccine for COVID-19) for participants in all age groups.Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately.DiscussionCOVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease.Systematic review registrationPROSPERO CRD42020196492
Platelet adhesion on commercially pure titanium plates in vitro III: effects of calcium phosphate-blasting on titanium plate biocompatibility
Authors: Nakamura Masayuki , Aizawa Hachidai , Kawabata Hideo , Sato Atsushi , Watanabe Taisuke , Isobe Kazushige , Kitamura Yutaka , Tanaka Takaaki , Kawase Tomoyuki 
Published: November 2020

Abstract
Background
Platelet-rich plasma (PRP) is often used to improve surface biocompatibility. We previously found that platelets rapidly adhere to plain commercially pure titanium (cp-Ti) plates in the absence, but not in the presence, of plasma proteins. To further expand on these findings, in the present study, we switched titanium plates from a plain surface to a rough surface that is blasted with calcium phosphate (CaP) powder and then examined platelet adhesion and activation.

Methods
Elemental distribution in CaP-blasted cp-Ti plates was analyzed using energy-dispersive X-ray spectroscopy. PRP samples prepared from anticoagulated blood samples of six healthy, non-smoking adult male donors were loaded on CaP-blasted cp-Ti plates for 1 h and fixed for examination of platelet morphology and visualization of PDGF-B and platelet surface markers (CD62P, CD63) using scanning electron microscopy and fluorescence microscopy. Plain SUS316L stainless steel plates used in injection needles were also examined for comparison.

Results
Significant amounts of calcium and phosphate were detected on the CaP-blasted cp-Ti surface. Platelets rapidly adhered to this surface, leading to higher activation. Platelets also adhered to the plain stainless surface; however, the levels of adhesion and activation were much lower than those observed on the CaP-blasted cp-Ti plate.

Conclusions
The CaP-blasted cp-Ti surface efficiently entraps and activates platelets. Biomolecules released from the activated platelets could be retained by the fibrin matrix on the surface to facilitate regeneration of the surrounding tissues. Thus, PRP immersion could not only eliminate surface air bubbles but also improve the biocompatibility of the implant surface.
Unmet need for family planning in Ethiopia and its association with occupational status of women and discussion to her partner: a systematic review and meta-analysis
Authors: Worku Solomon Adanew , Mittiku Yohannes Moges , Wubetu Abate Dargie 
Published: November 2020

AbstractBackgroundUnmet need refers to fecund women who either wish to postpone the next birth (spacers) or who wish to stop childbearing (limiters) but are not using a contraceptive method. Many women who are sexually active would prefer to avoid becoming pregnant but are not using any method of contraception. These women are considered to have an unmet need for family planning. Therefore, the objective of this systematic review and meta-analysis is to estimate the pooled prevalence of unmet need for family planning and its association to occupational status of women and discussion to her partner among fecund women in Ethiopia.MethodA systemic review and meta-analysis was conducted using published and unpublished research on the prevalence of unmet need for family planning and its association to occupational status of women and discussion to her partner among fecund women in Ethiopia. Data extraction was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were accessed through electronic web-based search from PubMed, Cochrane Library, Google Scholar, CINAHL, and Embase. All statistical analysis were done using STATA version 14 software using random effects model. The pooled prevalence was presented in forest plots.ResultsA total of 9 studies with 9785 participants were included, and the overall pooled estimated prevalence of unmet need for family planning among fecund women in Ethiopia was 34.90% (95% CI: 24.52, 45.28%). According to subgroup analysis the estimated prevalence of unmet need for family planning in studies conducted in Amhara was 32.98% (95% CI: 21.70, 44.26%), and among married women was 32.84% (95% CI: 16.62, 49.07%). Additionally, housewife women were 1.6 times more likely have unmet need for family planning compared to government employed women (OR: 1.6, 95% CI: 1.29, 1.99). Moreover, women who don’t discuss to partner were 1.87 times more likely to have unmet need for family planning compared to women who had discussion to her partner (OR 1.87; 95% CI: 1.52, 2.31).ConclusionThe analysis revealed that the overall prevalence of unmet need for family planning among fecund women in Ethiopia was high. Family planning programs should identify strategies to improve communication in family planning among couples and to ensure better cooperation between partners.
Medicine recalls in Saudi Arabia: a retrospective review of drug alerts (January 2010–January 2019)
Authors: AlQuadeib Bushra T. , Alfagih Iman M. , Alnahdi Ameera H. , Alharbi Shadia M. , Al-ahmari Rawan A. 
Published: November 2020

Abstract
Background
A new incidence of a substandard medicinal product is discovered weekly as stated by the World Health Organization (WHO) around the world. After discovering an incidence of a substandard medicinal product, a drug recall announced to remove the affected medicinal product from the market. Drug recalls in SaudiArabia (SA) are made by the Saudi Food and Drug Authority (SFDA) or the distributors of the drug when certain criteria are met. A retrospective study of drug recalls in SA was carried out. Data were collected through a website search of the SFDA for drug recalls since January 2010–January 2019.

Results
SFDA recalled 84 substandard medicinal products which related to 47 alert letters and 52 drugs. The number of drug recall reported by SFDA increased six-folds in 2018 than in 2010. The major frequent therapeutic class of drug recall was the antihypertensive drugs followed by the antibiotic drugs (27.7% and 10.8%, respectively). The majority of the recalls were tablets followed by parenteral dosage forms (58% and 25%, respectively). The major reasons for the drug recalls were due to contamination (32.14%) followed by non-compliance with manufacturer’s specifications (20.48%). Two manufacturers were accounted for 34.52% of all recalled drugs.

Conclusion
Substandard medicinal products are considered as a serious problem in SA. Contamination was the main cause of drug recalls, which requires root investigation of causes and for strict protective tools to be applied by drug manufacturers.