bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse events following third dose of mRNA COVID‐19 vaccination among nursing home residents who received the primary series
Authors: Bardenheier Barbara H. , White Elizabeth M. , Blackman Carolyn , Gravenstein Stefan , Gutman Roee , Sarkar Indra Neil , Feifer Richard A. , McConeghy Kevin , Nanda Aman , Duprey Matthew , Mor Vincent 
Published: April 2022

AbstractBackgroundWe sought to compare rates of adverse events among nursing home residents who received an mRNA COVID‐19 vaccine booster dose with those who had not yet received their booster.MethodsWe assessed a prospective cohort of 11,200 nursing home residents who received a primary COVID‐19 mRNA vaccine series at least 6 months prior to September 22, 2021 and received a third “booster dose” between September 22, 2021 and February 2, 2022. Residents lived in 239 nursing homes operated by Genesis HealthCare, spanning 21 U.S. states. We screened electronic health records for 20 serious vaccine‐related adverse events that are monitored following receipt of COVID‐19 vaccination by the CDC's Vaccine Safety Datalink. We matched boosted and yet‐to‐be boosted residents during the same time period, comparing rates of events occurring 14 days after booster administration with those occurring 14 days prior to booster administration. To supplement previously reported background rates of adverse events, we report background rates of medical conditions among nursing home residents during 2020, before COVID‐19 vaccines were administered in nursing homes. Events occurring in 2021–2022 were confirmed by physician chart review. We report unadjusted rates of adverse events and used a false discovery rate procedure to adjust for multiplicity of events tested.ResultsNo adverse events were reported during the 14 days post‐booster. A few adverse events occurred prior to booster (ischemic stroke: 49.4 per 100,000 residents, 95% CI: 21.2, 115.7; venous thromboembolism: 9.9 per 100,000 residents, 95% CI: 1.7, 56.0), though differences in event rates pre‐ versus post‐booster were not statistically significant (p < 0.05) after adjusting for multiple comparisons. No significant differences were detected between post‐booster vaccination rates and prior year 14‐day background rates of medical conditions.ConclusionsNo safety signals were detected following a COVID‐19 mRNA vaccine booster dose in this large multi‐state sample of nursing home residents.
Age‐related differences in symptoms in older emergency department patients with COVID‐19: Prevalence and outcomes in a multicenter cohort
Authors: Goldberg Elizabeth M. , Southerland Lauren T. , Meltzer Andrew C. , Pagenhardt Justine , Hoopes Ryan , Camargo Carlos A. , Kline Jeffrey A. 
Published: April 2022

AbstractBackgroundOlder adults represent a disproportionate share of severe COVID‐19 presentations and fatalities, but we have limited understanding of the differences in presentation by age and the association between less typical emergency department (ED) presentations and clinical outcomes.MethodsThis retrospective cohort study used the RECOVER Network registry, a research collaboration of 86 EDs in 27 U.S. states. We focused on encounters with a positive nasopharyngeal swab for SARS‐CoV‐2, and described their demographics, clinical presentation, and outcomes. Sequential multivariable logistic regressions examined the strength of association between age cohort and outcomes.ResultsOf 4536 encounters, median patient age was 55 years, 49% were women, and 34% were non‐Hispanic Black persons. Cough was the most common presenting complaint across age groups (18–64, 65–74, and 75+): 71%, 67%, and 59%, respectively (p < 0.001). Neurological symptoms, particularly altered mental status, were more common in older adults (2%, 11%, 26%; p < 0.001). Patients 75+ had the greatest odds of ED index visit admission of all age groups (adjusted odds ratio [aOR] 6.66; 95% CI 5.23–8.56), 30‐day hospitalization (aOR 7.44; 95% CI 5.63–9.99), and severe COVID‐19 (aOR 4.26; 95% CI 3.45–5.27). Compared to individuals with alternate presentations and adjusting for age, patients with typical symptoms (fever, cough and/or shortness of breath) had similar odds of ED index visit admission (aOR 1.01; 95% CI 0.81–1.24), potentially higher odds of 30‐day hospitalization (aOR 1.23; 95% CI 1.00–1.53), and greater odds of severe COVID‐19 (aOR 1.46; 95% CI 1.12–1.90).ConclusionsOlder patients with COVID‐19 are more likely to have presentations without the most common symptoms. However, alternate presentations of COVID‐19 in older ED patients are not associated with greater odds of mechanical ventilation and/or death. Our data highlights the importance of a liberal COVID‐19 testing strategy among older ED patients to facilitate accurate diagnoses and timely treatment and prophylaxis.
Estrogenic regulation of reproduction and energy homeostasis by a triumvirate of hypothalamic arcuate neurons
Authors: Stincic Todd L. , Kelly Martin J. 
Published: April 2022

AbstractPregnancy is energetically demanding and therefore, by necessity, reproduction and energy balance are inextricably linked. With insufficient or excessive energy stores a female is liable to suffer complications during pregnancy or produce unhealthy offspring. Gonadotropin‐releasing hormone neurons are responsible for initiating both the pulsatile and subsequent surge release of luteinizing hormone to control ovulation. Meticulous work has identified two hypothalamic populations of kisspeptin (Kiss1) neurons that are critical for this pattern of release. The involvement of the hypothalamus is unsurprising because its quintessential function is to couple the endocrine and nervous systems, coordinating energy balance and reproduction. Estrogens, more specifically 17β‐estradiol (E2), orchestrate the activity of a triumvirate of hypothalamic neurons within the arcuate nucleus (ARH) that govern the physiological underpinnings of these behavioral dynamics. Arising from a common progenitor pool, these cells differentiate into ARH kisspeptin, pro‐opiomelanocortin (POMC), and agouti related peptide/neuropeptide Y (AgRP) neurons. Although the excitability of all these subpopulations is subject to genomic and rapid estrogenic regulation, Kiss1 neurons are the most sensitive, reflecting their integral function in female fertility. Based on the premise that E2 coordinates autonomic functions around reproduction, we review recent findings on how Kiss1 neurons interact with gonadotropin‐releasing hormone, AgRP and POMC neurons, as well as how the rapid membrane‐initiated and intracellular signaling cascades activated by E2 in these neurons are critical for control of homeostatic functions supporting reproduction. In particular, we highlight how Kiss1 and POMC neurons conspire to inhibit AgRP neurons and diminish food motivation in service of reproductive success.
The lived experience of adults and parents: Transitioning from paediatric to adult health care with oesophageal atresia and tracheo‐oesophageal fistula
Authors: Haig‐Ferguson Andrew , Wallace Vuokko , Davis Cara 
Published: April 2022

AbstractAim and ObjectiveTo explore the experience of healthcare transition from paediatric to adult health care for adults born with oesophageal atresia and tracheo‐oesophageal fistula (OA/TOF) and parents.BackgroundOA/TOF is a rare and chronic health condition that can require lifelong medical follow‐up and management. There is evidence to suggest that transitioning from paediatric to adult health care can be problematic for people with rare and chronic conditions, including OA/TOF. The previous literature suggests that the experience of transitioning with a rare condition is more complex than transitioning with a common chronic condition.DesignThe current study was a qualitative, cross‐sectional, survey‐based study.MethodsData were collected through an online survey. Parents of children born with OA/TOF (n = 23) and adults born with OA/TOF (n = 16) were recruited through a UK‐based OA/TOF patient charity. Data from six open‐ended questions were analysed using a hybrid approach combining elements of inductive and deductive thematic analyses. Throughout the research process, the SRQR were followed.ResultsFive themes were constructed during the analysis, reflecting the experience of parents and adults transitioning from paediatric to adult health care: thrown into the unknown; a cultural shift; stepping back and stepping up; ‘no transition as such’; and living with uncertainty.ConclusionsThe findings suggested that a formalised, managed healthcare transition is not commonly experienced by people born with OA/TOF and parents.Relevance to Clinical PracticeWe recommend a formalised healthcare transition process in OA/TOF, including preparation for transition and having a named key worker to manage the multidisciplinary transition process. The results also highlighted the need for adults born with OA/TOF to have access to a specialist health service with knowledge and understanding of issues related to OA/TOF.
Comparison of the modified laparoscopic Vecchietti and Davydov colpoplasty techniques in Mayer‐Rokitansky‐Küster‐Hauser syndrome: A long‐term follow‐up analysis
Authors: Yang Xinyun , Zhu Linling , Wang Yan Jing , Tong Baoqin , Zhong Shuangshuang , Yang Chunbo , Liang Junxiao , Jin Hangmei , Xie Zhenwei 
Published: April 2022

AbstractAimsTo introduce and compare the modified laparoscopic Vecchietti and Davydov techniques for vaginoplasty in patients with Mayer‐Rokitansky‐Küster‐Hauser (MRKH) syndrome. Moreover, the long‐term treatment of vaginal agenesis was followed‐up.MethodsThis comparative retrospective cohort study enrolled a total of 53 women with MRKH syndrome. The patients underwent surgical creation of a neovagina including 32 patients who underwent the modified laparoscopic Vecchietti technique, and 21 patients who underwent the modified laparoscopic Davydov technique from January 2009 to February 2019. The perioperative parameters, complications, anatomical, and functional outcomes of the two groups were compared. Patients' sexual functions were evaluated over a long‐term follow‐up using the female sexual function index (FSFI) and the revised female sexual distress scale (FSDS‐R).ResultsThe medians (25th–75th) of the surgery duration for modified Vecchietti procedures was 50.0 (40.0–59.0) minutes, comparing to 135.0 (117.5–162.5) min for Davydov procedures (p < 0.001). The intraoperative blood loss was 20 (7.5–20.0) mL versus 50.0 (50.0–100.0) mL using the modified Vecchietti and Davydov approaches (p < 0.001), respectively. In the 39 follow‐up cases, the lengths of the neovagina of the patients for Vecchietti group versus Davydov group were 7.9 ± 1.0 cm versus 8.6 ± 1.2 cm at 6 months after the vaginoplasty and 8.3 ± 0.7 cm versus 8.5 ± 0.9 cm after 2 years. There was no statistical difference in the FSFI and FSDS‐R scores between the two groups.ConclusionsBoth the modified Davydov and Vecchietti laparoscopic procedures successfully achieved optimal anatomic and functional outcomes in treatments of vaginal agenesis. The modified Vecchietti technique is relatively simpler than the modified Davydov technique.
Iron deficiency screening is a key issue in chronic inflammatory diseases: A call to action
Authors: Cacoub Patrice , Choukroun Gabriel , Cohen‐Solal Alain , Luporsi Elisabeth , Peyrin‐Biroulet Laurent , Peoc'h Katell , Andrieu Valérie , Lasocki Sigismond , Puy Hervé , Trochu Jean‐Noël 
Published: April 2022

AbstractIron deficiency is frequent in patients with chronic inflammatory conditions (e.g., chronic heart failure, chronic kidney disease, cancers, and bowel inflammatory diseases). Indeed, high concentrations of inflammatory cytokines increase hepcidin concentrations that lead to the sequestration of iron in cells of the reticuloendothelial system (functional iron deficiency). Iron parameters are often assessed only in the context of anemia, but iron deficiency, even without anemia, is present in about half of patients with inflammatory conditions. Iron deficiency worsens underlying chronic diseases and is an independent factor of morbidity and mortality. In daily practice, the most effective biomarkers of iron status are serum ferritin, which reflects iron storage, and transferrin saturation, which reflects the transport of iron. Serum ferritin is increased in an inflammatory context, and there is still no consensus on the threshold to be used in chronic inflammatory conditions. Nevertheless, recent recommendations of international guidelines agreed to define iron deficiency by serum ferritin <100 µg/L and/or transferrin saturation <20%. Iron parameters remain, however, insufficiently assessed in patients with chronic inflammatory conditions. Indeed, clinical symptoms of iron deficiency, such as fatigue, are not specific and often confused with those of the primary disease. Iron repletion, preferably by the intravenous route to bypass tissue sequestration, improves clinical signs and quality of life. Because of the negative impact of iron deficiency on chronic inflammatory diseases and the efficacy of intravenous iron repletion, screening of iron parameters should be part of the routine examination of all patients with chronic inflammatory diseases.
Immunoexpression of oral brush biopsy enhances the accuracy of diagnosis for oral lichen planus and lichenoid lesions
Authors: Idrees Majdy , Shearston Kate , Farah Camile S. , Kujan Omar 
Published: April 2022

AbstractBackgroundThis study assessed the efficacy of using oral liquid‐based brush cytology (OLBC) coupled with immunostained cytology‐derived cell‐blocks, quantified using machine‐learning, in the diagnosis of oral lichen planus (OLP).MethodsEighty‐two patients diagnosed clinically with either OLP or oral lichenoid lesion (OLL) were included. OLBC samples were obtained from all patients before undergoing surgical biopsy. Liquid‐based cytology slides and cell‐blocks were prepared and assessed by cytomorphology and immunocytochemistry for four antibodies (Ki‐67, BAX, NF‐κB‐p65, and AMACR). For comparison purposes, a sub‐group of 31 matched surgical biopsy samples were selected randomly and assessed by immunohistochemistry. Patients were categorized according to their definitive diagnoses into OLP, OLL, and clinically lichenoid, but histopathologically dysplastic lesions (OEDL). Machine‐learning was utilized to provide automated quantification of positively stained protein expression.ResultsCytomorphological assessment was associated with an accuracy of 77.27% in the distinction between OLP/OLL and OEDL. A strong concordance of 92.5% (κ = 0.84) of immunostaining patterns was evident between cell‐blocks and tissue sections using machine‐learning. A diagnostic index using a Ki‐67‐based model was 100% accurate in detecting lichenoid cases with epithelial dysplasia. A BAX‐based model demonstrated an accuracy of 92.16%. The accuracy of cytomorphological assessment was greatly improved when it was combined with BAX immunoreactivity (95%).ConclusionsCell‐blocks prepared from OLBC are reliable and minimally‐invasive alternatives to surgical biopsies to diagnose OLLs with epithelial dysplasia when combined with Ki‐67 immunostaining. Machine‐learning has a promising role in the automated quantification of immunostained protein expression.
Entrepreneurship and new product development: Exploring the “advantage of youth” and “business acumen” views
Authors: Grilli Luca 
Published: April 2022

AbstractWe explore the relevance of two different views on new product development (NPD) drivers, defined as “advantage of youth” and “business acumen.” The two arguments, that establish a negative relationship between an individual's age and NPD and a positive impact of professional experience on NPD, are theoretically contextualized and empirically tested in the entrepreneurship domain. Considering a sample of more than 4000 Italian entrepreneurs of innovative start‐ups, a series of econometric analyses confirm that both effects apply and reveal interesting nuances as to the relevance of the age effect and the relative importance of different dimensions of entrepreneurs' business acumen on NPD. Further additional analyses highlight how both the “advantage of youth” and “business acumen” do not necessarily lead to successful entrepreneurial NPD, but at the same time, they both are found to importantly characterize top performers among entrepreneurs engaging in NPD. Overall, this in‐depth analysis on entrepreneurial NPD and its drivers underlies the importance of a micro‐founded and individual‐based approach in the study of new product dynamics, and in doing so, it contributes to enrich the upper echelons perspective and related frameworks on innovation outcomes through entrepreneurship. By theorizing and documenting those personal demographic and human capital traits which are mostly associated with entrepreneurial NPD, a series of interesting implications quite naturally descend for several stakeholders: (prospective) entrepreneurs, managers who aim at nurturing an intrapreneurship culture within their companies and policy makers interested in increasing dynamic efficiency in the economic system through the launch of new products and services.
Insomnia disorder: State of the science and challenges for the future
Authors: Riemann Dieter , Benz Fee , Dressle Raphael J. , Espie Colin A. , Johann Anna F. , Blanken Tessa F. , Leerssen Jeanne , Wassing Rick , Henry Alasdair L. , Kyle Simon D. , Spiegelhalder Kai , Van Someren Eus J. W. 
Published: April 2022

SummaryInsomnia disorder comprises symptoms during night and day that strongly affect quality of life and wellbeing. Prolonged sleep latency, difficulties to maintain sleep and early morning wakening characterize sleep complaints, whereas fatigue, reduced attention, impaired cognitive functioning, irritability, anxiety and low mood are key daytime impairments. Insomnia disorder is well acknowledged in all relevant diagnostic systems: Diagnostic and Statistical Manual of the American Psychiatric Association, 5th revision, International Classification of Sleep Disorders, 3rd version, and International Classification of Diseases, 11th revision. Insomnia disorder as a chronic condition is frequent (up to 10% of the adult population, with a preponderance of females), and signifies an important and independent risk factor for physical and, especially, mental health. Insomnia disorder diagnosis primarily rests on self‐report. Objective measures like actigraphy or polysomnography are not (yet) part of the routine diagnostic canon, but play an important role in research. Disease concepts of insomnia range from cognitive‐behavioural models to (epi‐) genetics and psychoneurobiological approaches. The latter is derived from knowledge about basic sleep–wake regulation and encompass theories like rapid eye movement sleep instability/restless rapid eye movement sleep. Cognitive‐behavioural models of insomnia led to the conceptualization of cognitive‐behavioural therapy for insomnia, which is now considered as first‐line treatment for insomnia worldwide. Future research strategies will include the combination of experimental paradigms with neuroimaging and may benefit from more attention to dysfunctional overnight alleviation of distress in insomnia. With respect to therapy, cognitive‐behavioural therapy for insomnia merits widespread implementation, and digital cognitive‐behavioural therapy may assist delivery along treatment guidelines. However, given the still considerable proportion of patients responding insufficiently to cognitive‐behavioural therapy for insomnia, fundamental studies are highly necessary to better understand the brain and behavioural mechanisms underlying insomnia. Mediators and moderators of treatment response/non‐response and the associated development of tailored and novel interventions also require investigation. Recent studies suggest that treatment of insomnia may prove to add significantly as a preventive strategy to combat the global burden of mental disorders.
Sleep medicine guidelines, recommendations for clinical practice: the role of the European Sleep Research Society
Authors: Penzel Thomas 
Published: April 2022

SummaryThe European Sleep Research Society (ESRS) has a strong focus on sleep research in Europe. In addition, the ESRS supports sleep medicine in Europe by providing a platform of exchange and communication for the national sleep societies of all European countries and by providing committees that support co‐ordination for important clinical activities. These committees help on clinical guidelines, certification of sleep centres, certification of sleep physicians, psychologists, sleep scientists, sleep technologists, and medical education in sleep medicine. For education in sleep medicine, a “Catalogue on knowledge and skills” has been developed based on a consensus process. This catalogue serves as the backbone for a European textbook on sleep medicine and as the basis for courses, qualifications, and examinations of somnologists in Europe. These activities are devoted to improving and maintain a high quality of care in Europe for sleep medicine services.
Pharmacology, safety, efficacy and clinical uses of the COX‐2 inhibitor robenacoxib
Authors: Lees Peter , Toutain Pierre‐Louis , Elliott Jonathan , Giraudel Jerome M. , Pelligand Ludovic , King Jonathan N. 
Published: April 2022

AbstractRobenacoxib is a veterinary‐approved non‐steroidal anti‐inflammatory drug (NSAID) of the coxib group. It possesses anti‐hyperalgesic, anti‐inflammatory and anti‐pyretic properties. Robenacoxib inhibits the cyclooxygenase (COX)‐2 isoform of COX selectively (in vitro IC50 ratios COX‐1:COX‐2, 129:1 in dogs, 32:1 in cats). At registered dosages (2 mg/kg subcutaneously in dogs and cats, 1–4 mg/kg orally in dogs and 1–2.4 mg/kg orally in cats), robenacoxib produces significant inhibition of COX‐2 whilst sparing COX‐1. The pharmacokinetic (PK) profile of robenacoxib is characterized by a high degree of binding to plasma proteins (>98%) and moderate volume of distribution (at steady state, 240 ml/kg in dogs and 190 ml/kg in cats). In consequence, the terminal half‐life in blood (<2 h) is short, despite moderate body clearance (0.81 L/kg/h) in dogs and low clearance (0.44 L/kg/h) in cats. Excretion is principally in the bile (65% in dogs and 72% in cats). Robenacoxib concentrates in inflamed tissues, and clinical efficacy is achieved with once‐daily dosing, despite the short blood terminal half‐life. In dogs, no relevant breed differences in robenacoxib PK have been detected. Robenacoxib has a wide safety margin; in healthy laboratory animals daily oral doses 20‐fold (dog, 1 month), eight‐fold (cat, 6 weeks) and five‐fold (dog, 6 months) higher than recommended clinical doses were well tolerated. Clinical efficacy and safety have been demonstrated in orthopaedic and soft tissue surgery, and in musculoskeletal disorders in dogs and cats.