bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Clinical Global Impression of Change (CGI-C) and a Caregiver Global Impression of Change (CaGI-C) measure for ambulant individuals with Duchenne muscular dystrophy
Authors: Staunton Hannah , Trennery Claire , Arbuckle Rob , Guridi Maitea , Zhuravleva Elena , Furlong Pat , Fischer Ryan , Hall Rebecca 
Published: July 2021

Abstract
Background
In clinical trials for rare diseases, such as Duchenne muscular dystrophy, clinical outcome assessments (COA) used to assess treatment benefit are often generic and may not be sensitive enough to detect change in specific patient populations. Thus, there is a need for disease specific COAs that track meaningful change among individuals. When developing such measures, input from clinicians, caregivers and patients is critical for assessing clinically relevant concepts and ensuring validity of the measure.

Method
The aim of this study was to develop two Duchenne-specific global impression items for use in clinical trials. The development of the Duchenne Clinical Global Impression of Change (CGI-C) and Caregiver Global Impression of Change (CaGI-C) was informed by findings from concept elicitation (CE) interviews with clinicians, caregivers and individuals with Duchenne. Through cognitive debriefing (CD) interviews, clinicians and caregivers evaluated draft CGI-C and CaGI-C items to ensure relevance and understanding of the items and instructions. Suggestions made during the CD interviews were incorporated into the finalized CGI-C and CaGI-C measures.

Results
The symptoms most frequently reported by clinicians, caregivers and individuals with Duchenne were muscle weakness, fatigue, cardiac difficulties and pain. Regarding physical functioning, all three populations noted that small changes in functional ability were meaningful, particularly when independence was impacted. Caregivers and clinicians reported that changes in speed, endurance and quality of movement were important, as was improvement in the ability of individuals to keep up with their peers. A change in the ability to complete everyday activities was also significant to families. These results were used to create two global impression of change items and instruction documents for use by clinicians (CGI-C) and caregivers (CaGI-C). Overall, both items were well understood by participants. The descriptions and examples developed from the CE interviews were reported to be relevant and appropriate for illustrating different levels of meaningful change in patients with Duchenne. Modifications were made based on caregiver and clinician CD feedback .

Conclusions
As part of a holistic measurement strategy, such COA can be incorporated into the clinical trial setting to assess global changes in relevant symptoms and functional impacts associated with Duchenne.
Incidence trends and survival prediction of urothelial cancer of the bladder: a population-based study
Authors: He Hairong , Liu Tianjie , Han Didi , Li Chengzhuo , Xu Fengshuo , Lyu Jun , Gao Ye 
Published: July 2021

Abstract
Background
The aim of this study is to determine the incidence trends of urothelial cancer of the bladder (UCB) and to develop a nomogram for predicting the cancer-specific survival (CSS) of postsurgery UCB at a population-based level based on the SEER database.

Methods
The age-adjusted incidence of UCB diagnosed from 1975 to 2016 was extracted, and its annual percentage change was calculated and joinpoint regression analysis was performed. A nomogram was constructed for predicting the CSS in individual cases based on independent predictors. The predictive performance of the nomogram was evaluated using the consistency index (C-index), net reclassification index (NRI), integrated discrimination improvement (IDI), a calibration plot and the receiver operating characteristics (ROC) curve.

Results
The incidence of UCB showed a trend of first increasing and then decreasing from 1975 to 2016. However, the overall incidence increased over that time period. The age at diagnosis, ethnic group, insurance status, marital status, differentiated grade, AJCC stage, regional lymph nodes removed status, chemotherapy status, and tumor size were independent prognostic factors for postsurgery UCB. The nomogram constructed based on these independent factors performed well, with a C-index of 0.823 and a close fit to the calibration curve. Its prediction ability for CSS of postsurgery UCB is better than that of the existing AJCC system, with NRI and IDI values greater than 0 and ROC curves exhibiting good performance for 3, 5, and 8 years of follow-up.

Conclusions
The nomogram constructed in this study might be suitable for clinical use in improving the clinical predictive accuracy of the long-term survival for postsurgery UCB.
Secondarily estimated cure fraction and five-year recurrence-free conditional survival probabilities among patients undergoing surgical resection for hepatocellular carcinoma presenting with minor gross vascular invasion
Authors: Bae Byungje , Song Sung Kyu , Choi Eunyoung , Chung Chul-Woon , Park Yongkeun 
Published: July 2021

Abstract
Background
Surgical resection (SR) has been selectively applied in hepatocellular carcinoma (HCC) presenting with minor gross vascular invasion (mGVI) which is defined when tumor invasion is confined to second-order portal branches or segmental branches of hepatic vein. However, little data of long-term outcomes are available for supporting the role of SR as a potentially curable therapeutic option for HCC presenting with mGVI. This study is aimed to estimate a statistical cure fraction and the improvement of recurrence-free conditional survival (RFCS) over time among patients undergoing SR for HCC presenting with mGVI.

Methods
The literature search was conducted focusing on previous studies that investigated the long-term survival rates of patients after SR for HCC presenting with mGVI. The reference cohort was extracted from a study including patients undergoing SR for HCC without vascular invasion. A non-mixture cure model was adopted to estimate the statistical cure fraction. The 5-year RFCS probabilities were also calculated.

Results
Three retrospective studies were secondarily analyzed. The probability of being statistically cured after SR for HCC presenting with mGVI was 7.3% (95% confidence interval, 4.4%–11.2%) in the mGVI group, lower than that of the reference cohort (hazard ratio, 1.81; 95% confidence interval, 1.59–2.05). The estimated 5-year RFCS probabilities improved with each additional year of survival. Moreover, 1 year after SR, the 5-year RFCS probabilities of patients with HCC presenting with mGVI was essentially the same as that of the reference cohort.

Conclusions
This study shows that a cure can be expected in around seven percent of patients undergoing SR for HCC presenting with mGVI. Furthermore, recurrence-free survival expectancy improves dramatically over time among those patients who do not have recurrence. Overall, these findings suggest that SR should be considered as a potentially curable treatment for patients with HCC presenting with mGVI.
More blastocysts are produced from fewer oocytes in ICSI compared to IVF – results from a sibling oocytes study and definition of a new key performance indicator
Authors: Chamayou Sandrine , Ragolia Carmen , Alecci Carmelita , Storaci Giorgia , Romano Simona , Sapienza Roberta , Maglia Elena , Liprino Annalisa , Cardea Clementina , Fichera Michele , Guglielmino Antonino 
Published: July 2021

Abstract
Background
Which fertilization method, between ICSI and IVF in split insemination treatments, has the highest clinical efficiency in producing clinically usable blastocyst?

Methods
211 infertile couples underwent split insemination treatments for a non-severe male factor. 1300 metaphase II (MII) oocytes were inseminated by conventional IVF and 1302 MII oocytes were micro-injected with the same partner’s semen. Embryo development until blastocyst stage on day V and clinical outcomes were valuated trough conventional key performance indicators (KPI), and new KPIs such as blastocyst rate per used MII oocytes and the number of MII oocytes to produce one clinically usable blastocyst from ICSI and IVF procedures.

Results
The results were globally analyzed and according to ovarian stimulation protocol, infertility indication, and female age. The conventional KPI were online with the expected values from consensus references. From global results, 2.3 MII oocyte was needed to produce one clinically usable blastocyst after ICSI compared to 2.9 MII oocytes in IVF. On the same way, more blastocysts for clinical use were produced from fewer MII oocytes in ICSI compared to IVF in all sub-groups.

Conclusions
In split insemination treatments, the yield of clinically usable blastocysts was always superior in ICSI compared to IVF. The new KPI "number of needed oocytes to produce one clinically usable embryo" tests the clinical efficiency of the IVF laboratory.
High-parameter cytometry unmasks microglial cell spatio-temporal response kinetics in severe neuroinflammatory disease
Authors: Spiteri Alanna G. , Terry Rachel L. , Wishart Claire L. , Ashhurst Thomas M. , Campbell Iain L. , Hofer Markus J. , King Nicholas J. C. 
Published: July 2021

AbstractBackgroundDifferentiating infiltrating myeloid cells from resident microglia in neuroinflammatory disease is challenging, because bone marrow-derived inflammatory monocytes infiltrating the inflamed brain adopt a ‘microglia-like’ phenotype. This precludes the accurate identification of either cell type without genetic manipulation, which is important to understand their temporal contribution to disease and inform effective intervention in its pathogenesis. During West Nile virus (WNV) encephalitis, widespread neuronal infection drives substantial CNS infiltration of inflammatory monocytes, causing severe immunopathology and/or death, but the role of microglia in this remains unclear.MethodsUsing high-parameter cytometry and dimensionality-reduction, we devised a simple, novel gating strategy to identify microglia and infiltrating myeloid cells during WNV-infection. Validating our strategy, we (1) blocked the entry of infiltrating myeloid populations from peripheral blood using monoclonal blocking antibodies, (2) adoptively transferred BM-derived monocytes and tracked their phenotypic changes after infiltration and (3) labelled peripheral leukocytes that infiltrate into the brain with an intravenous dye. We demonstrated that myeloid immigrants populated only the identified macrophage gates, while PLX5622 depletion reduced all 4 subsets defined by the microglial gates.ResultsUsing this gating approach, we identified four consistent microglia subsets in the homeostatic and WNV-infected brain. These were P2RY12hiCD86−, P2RY12hiCD86+and P2RY12loCD86−P2RY12loCD86+. During infection, 2 further populations were identified as 'inflammatory' and 'microglia-like' macrophages, recruited from the bone marrow. Detailed kinetic analysis showed significant increases in the proportions of both P2RY12lomicroglia subsets in all anatomical areas, largely at the expense of the P2RY12hiCD86−subset, with the latter undergoing compensatory proliferation, suggesting replenishment of, and differentiation from this subset in response to infection. Microglia altered their morphology early in infection, with all cells adopting temporal and regional disease-specific phenotypes. Late in disease, microglia produced IL-12, downregulated CX3CR1, F4/80 and TMEM119 and underwent apoptosis. Infiltrating macrophages expressed both TMEM119 and P2RY12 de novo, with the microglia-like subset notably exhibiting the highest proportional myeloid population death.ConclusionsOur approach enables detailed kinetic analysis of resident vs infiltrating myeloid cells in a wide range of neuroinflammatory models without non-physiological manipulation. This will more clearly inform potential therapeutic approaches that specifically modulate these cells.
Investigation of common risk factors between polycystic ovary syndrome and Alzheimer’s disease: a narrative review
Authors: Sarahian Nahid , Sarvazad Hosna , Sajadi Elham , Rahnejat Nasrin , Eskandari Roozbahani Narges 
Published: July 2021

Abstract
Background
The most common endocrine and metabolic disorders in premenopausal women is polycystic ovary syndrome (PCOS), characterized by hyperandrogenism, chronic anovulation, and/or ultrasound evidence of small ovarian cysts. Obesity and insulin resistance are also the main factors influencing the clinical manifestations of this syndrome. Alzheimer’s disease (AD) is the most typical progressive neurodegenerative disorder of the brain, and recent studies suggest a relationship between endocrinal dysregulation and neuronal loss during AD pathology.

Aim
This study aimed to evaluate the common risk factors for Alzheimer’s and PCOS based on previous studies. Knowing the common risk factors and eliminating them may prevent neurodegenerative Alzheimer’s disease in the future.

Method
In this narrative review, international databases, including Google Scholar, Scopus, PubMed, and the Web of Science, were searched to retrieve the relevant studies. The relevant studies’ summaries were categorized to discuss the possible pathways that may explain the association between Alzheimer’s and PCOS signs/symptoms and complications.

Results
According to our research, the factors involved in Alzheimer’s and PCOS disorders may share some common risk factors. In patients with PCOS, increased LH to FSH ratio, decreased vitamin D, insulin resistance, and obesity are some of the most important factors that may increase the risk of Alzheimer’s disease.
Global infectious disease research collaborations in crises: building capacity and inclusivity through cooperation
Authors: Fanning Jonathon P. , Murthy Srinivas , Obonyo Nchafatso G. , Baillie J. Kenneth , Webb Steve , Dalton Heidi J. , Fraser John F. 
Published: July 2021

Abstract
Background
The initial research requirements in pandemics are predictable. But how is it possible to study a disease that is so quickly spreading and to rapidly use that research to inform control and treatment?

Main body
In our view, a dilemma with such wide-reaching impact mandates multi-disciplinary collaborations on a global scale. International research collaboration is the only means to rapidly address these fundamental questions and potentially change the paradigm of data sharing for the benefit of patients throughout the world. International research collaboration presents significant benefits but also barriers that need to be surmounted, especially in low- and middle-income countries.

Conclusion
Facilitating international cooperation, by building capacity in established collaborative platforms and in low- and middle-income countries, is imperative to efficiently answering the priority clinical research questions that can change the trajectory of a pandemic.
Impact of a “vegetables first” approach to complementary feeding on later intake and liking of vegetables in infants: a study protocol for a randomised controlled trial
Authors: Rapson Jeanette P. , von Hurst Pamela R. , Hetherington Marion M. , Conlon Cathryn A. 
Published: July 2021

Abstract
Background
Vegetables as first complementary foods for infants may programme taste preferences that lead to improved vegetable intake in children. Yet few studies have investigated the impact of a ”vegetables first” approach to complementary feeding, especially in New Zealand. The purpose of this randomised control trial is to investigate the effect of starting complementary feeding with vegetables only on infants’ later intake and liking of vegetables, compared to those starting with fruit and vegetables.

Methods/design
One-hundred and twenty mother-infant pairs living in Auckland, New Zealand, will be randomised to receive either vegetables only (intervention) or fruit and vegetables (control) for 28 days, starting from the first day of complementary feeding at around 4–6 months of age. Infants will be presented with a brassica (broccoli), followed by a green leafy vegetable (spinach) and sweet fruit (pear) at 9 months of age. The primary outcome measures of intake of each food will be assessed using a weighed food diary. Secondary outcome measures of overall intake, liking and wanting of vegetables will be assessed using a food frequency questionnaire, liking tool and video coding tool, respectively, at 9, 12, and 24 months of age. Infant growth and iron status will be assessed as part of health screening and monitoring at baseline, post intervention and 9 months of age. Other biological samples to be collected include infant stool samples, vitamin D (mother and infant), iron status (mother), and mothers’ diet.

Discussion
This randomised, controlled trial will be the first to our knowledge to investigate a “vegetables first” approach to complementary feeding on infants’ liking and intake of vegetables in New Zealand. Comparison against standard practice (fruit and vegetables as first foods) should complement other trials underway, such as the Baby’s First Bites and Nordic OTIS trial. Results may contribute to the evidence supporting complementary feeding guidelines in New Zealand and worldwide.

Trial registration
Australian New Zealand Clinical Trial Registry ACTRN12619000737134. Registered on 16 May 2019.
The Community PrEP Study: a randomized control trial leveraging community-based platforms to improve access and adherence to pre-exposure prophylaxis to prevent HIV among adolescent girls and young women in South Africa—study protocol
Authors: Medina-Marino Andrew , Bezuidenhout Dana , Hosek Sybil , Barnabas Ruanne V. , Atujuna Millicent , Bezuidenhout Charl , Ngwepe Phuti , Peters Remco P.H. , Little Francesca , Celum Connie L. , Daniels Joseph , Bekker Linda-Gail 
Published: July 2021

AbstractBackgroundHIV incidence among South African adolescent girls and young women (AGYW) remains high, but could be reduced by highly effective pre-exposure prophylaxis (PrEP). Unfortunately, AGYW report significant barriers to clinic-based sexual and reproductive health services. Even when AGYW access PrEP as an HIV prevention method, poor prevention-effective use was a serious barrier to achieving its optimal HIV prevention benefits. Determining the acceptability and feasibility of community-based platforms to increase AGYW’s access to PrEP, and evaluating behavioural interventions to improve prevention-effective use of PrEP are needed.MethodsWe propose a mixed-methods study among AGYW aged 16–25 years in Eastern Cape Province, South Africa. In the first component, a cross-sectional study will assess the acceptability and feasibility of leveraging community-based HIV counselling and testing (CBCT) platforms to refer HIV-negative, at-risk AGYW to non-clinic-based, same-day PrEP initiation services. In the second component, we will enrol 480 AGYW initiating PrEP via our CBCT platforms into a three-armed (1:1:1) randomized control trial (RCT) that will evaluate the effectiveness of adherence support interventions to improve the prevention-effective use of PrEP. Adherence will be measured over 24 months via tenofovir-diphosphate blood concentration levels. Qualitative investigations will explore participant, staff, and community experiences associated with community-based PrEP services, adherence support activities, study implementation, and community awareness. Costs and scalability of service platforms and interventions will be evaluated.DiscussionThis will be the first study to assess the acceptability and feasibility of leveraging CBCT platforms to identify and refer at-risk AGYW to community-based, same-day PrEP initiation services. It will also provide quantitative and qualitative results to inform adherence support activities and services that promote the prevention-effective use of PrEP among AGYW. By applying principles of implementation science, behavioural science, and health economics research, we aim to inform strategies to improve access to and prevention-effective use of PrEP by AGYW.Trial registrationClinicalTrials.govNCT03977181. Registered on 6 June 2019—retrospectively registered.
Effects of early respiratory physiotherapy on spontaneous respiratory activity of preterm infants: study protocol for a randomized controlled trial
Authors: Di Polito Alessia , Del Vecchio Arianna , Tana Milena , Papacci Patrizia , Vento Anna Laura , Campagnola Benedetta , Celona Sefora , Cricenti Laura , Bastoni Ilaria , Tirone Chiara , Lio Alessandra , Aurilia Claudia , Bottoni Anthea , Paladini Angela , Cota Francesco , Ferrara Paola Emilia , Ronconi Gianpaolo , Vento Giovanni 
Published: July 2021

Abstract
Background
Tactile maneuvers stimulating spontaneous respiratory activity in preterm infants are recommended since birth, but data on how and how often these maneuvers are applied in clinical practice are unknown. In the last years, most preterm newborns with respiratory failure are preferentially managed with non-invasive respiratory support and by stimulating spontaneous respiratory activity from the delivery room and in neonatal intensive care unit (NICU), in order to avoid the risks of intubation and prolonged mechanical ventilation.

Methods
Preterm infants with gestational age < 31 weeks not intubated in the delivery room and requiring non-invasive respiratory support at birth will be eligible for the study. They will be randomized and allocated to one of two treatment groups: (1) the study group infants will be subject to the technique of respiratory facilitation within the first 24 h of life, according to the reflex stimulations, by the physiotherapist. The newborn is placed in supine decubitus and a slight digital pressure is exerted on a hemithorax. The respiratory facilitation technique will be performed for about three minutes and repeated for a total of 4/6 times in sequence, three times a day until spontaneous respiratory activity is achieved; thus, no respiratory support is required; (2) the control group infants will take part exclusively in the individualized postural care program. They will perform the technique of respiratory facilitation and autogenous drainage.

Objective
To evaluate the efficacy of early respiratory physiotherapy in reducing the incidence of intubation and mechanical ventilation in the first week of life (primary outcome).

Discussion
The technique of respiratory facilitation is based on reflex stimulations, applied early to preterm infant. Slight digital pressure is exerted on a “trigger point” of each hemithorax, to stimulate the respiratory activity with subsequent increase of the ipsilateral pulmonary minute ventilation and to facilitate the contralateral pulmonary expansion. This mechanism will determine the concatenation of input to all anatomical structures in relation to the area being treated, to promote spontaneous respiratory activity and reducing work of breathing, avoiding or minimizing the use of invasive respiratory support.

Trial registration
UMIN-CTR Clinical Trial UMIN000036066. Registered on March 1, 2019. Protocol 1. https://www.umin.ac.jp/ctr