bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic performance of automated, streamlined, daily updated exome analysis in patients with neurodevelopmental delay
Authors: Seo Go Hun , Lee Hane , Lee Jungsul , Han Heonjong , Cho You Kyung , Kim Minji , Choi Yunha , Choi Jeongmin , Choi In Hee , Rhie Seonkyeong , Chae Kyu Young , Kim Yoo-Mi , Cheon Chong Kun , Kim Su Jin , Lee Jieun , Kang Eungu , Byeon Jung Hye , Yu Hee Joon , Shin Young-Lim , Oh Arum , Kim Woo Jin , Yum Mi-Sun , Lee Beom Hee , Eun Baik-Lin 
Published: March 2022

AbstractBackgroundThe diagnostic yield of whole-exome sequencing (WES) varies from 30%–50% among patients with mild to severe neurodevelopmental delay (NDD)/intellectual disability (ID). Routine retrospective reanalysis of undiagnosed patients has increased the total diagnostic yield by 10–15%. Here, we performed proband-only WES of 1065 patients with NDD/ID and applied a prospective, daily reanalysis automated pipeline to patients without clinically significant variants to facilitate diagnoses.MethodsThe study included 1065 consecutive patients from 1056 nonconsanguineous unrelated families from 10 multimedical centers in South Korea between April 2018 and August 2021. WES data were analyzed daily using automatically updated databases with variant classification and symptom similarity scoring systems.ResultsAt the initial analysis, 402 patients from 1056 unrelated families (38.0%, 402/1,056 families) had a positive genetic diagnosis. Daily prospective, automated reanalysis resulted in the identification of 34 additional diagnostic variants in 31 patients (3%), which increased our molecular diagnostic yield to 41% (433/1056 families). Among these 31 patients, 26 were diagnosed with 23 different diseases that were newly discovered after 2019. The time interval between the first analysis and the molecular diagnosis by reanalysis was 1.2 ± 0.9 years, which was shorter in the patients enrolled during the latter part of the study period.ConclusionDaily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information.
Differential expression of enzymes in thymidylate biosynthesis in zebrafish at different developmental stages: implications for dtymk mutation-caused neurodegenerative disorders
Authors: Frisk Junmei Hu , Örn Stefan , Pejler Gunnar , Eriksson Staffan , Wang Liya 
Published: March 2022

Abstract
Background
Deoxythymidine triphosphate (dTTP) is an essential building block of DNA, and defects in enzymes involved in dTTP synthesis cause neurodegenerative disorders. For instance, mutations in DTYMK, the gene coding for thymidylate kinase (TMPK), cause severe microcephaly in human. However, the mechanism behind this is not well-understood. Here we used the zebrafish model and studied (i) TMPK, an enzyme required for both the de novo and the salvage pathways of dTTP synthesis, and (ii) thymidine kinases (TK) of the salvage pathway in order to understand their role in neuropathology.

Results
Our findings reveal that maternal-stored dNTPs are only sufficient for 6 cell division cycles, and the levels of dNTPs are inversely correlated to cell cycle length during early embryogenesis. TMPK and TK activities are prominent in the cytosol of embryos, larvae and adult fish and brain contains the highest TMPK activity. During early development, TMPK activity increased gradually from 6 hpf and a profound increase was observed at 72 hpf, and TMPK activity reached its maximal level at 96 hpf, and remained at high level until 144 hpf. The expression of dtymk encoded Dtymk protein correlated to its mRNA expression and neuronal development but not to the TMPK activity detected. However, despite the high TMPK activity detected at later stages of development, the Dtymk protein was undetectable. Furthermore, the TMPK enzyme detected at later stages showed similar biochemical properties as the Dtymk enzyme but was not recognized by the Dtymk specific antibody.

Conclusions
Our results suggest that active dNTP synthesis in early embryogenesis is vital and that Dtymk is essential for neurodevelopment, which is supported by a recent study of dtymk knockout zebrafish with neurological disorder and lethal outcomes. Furthermore, there is a novel TMPK-like enzyme expressed at later stages of development.
Effectiveness of single loading dose of dexmedetomidine combined with propofol for deep sedation of endoscopic retrograde cholangiopancreatography (ERCP) in elderly patients: a prospective randomized study
Authors: Chen Mo , Sun Yi , Li Xueyan , Zhang Chun , Huang Xiaochen , Xu Yiming , Gu Chengyong 
Published: March 2022

Abstract
Background
Endoscopic retrograde cholangiopancreatography (ERCP) is an advanced endoscopic procedure and requires deep sedation. Deep sedation with dexmedetomidine for the respiratory drive preserved has become popular in recent years. However, the use of dexmedetomidine in elderly patients is controversial because its adverse events are more common. The objective of this study was to investigate the effectiveness of a single loading dose of dexmedetomidine combined with propofol for deep sedation of ERCP in elderly patients.

Methods
In this prospective randomized trial, 49 elderly patients undergoing ERCP were randomly allocated to the dexmedetomidine (DEX) or propofol (PRO) groups. The single loading dose of dexmedetomidine was set at 0.5 μg/kg at the start of anesthesia induction and loading for 10 min. The primary outcome was the cumulative dose of propofol. Secondary outcomes included time to awake, the frequency of airway interventions, and hemodynamics.

Results
The intraoperative cumulative dose of propofol was lower in the DEX group (111.0 ± 12.6 μg/kg/min) than the PRO group (143.7 ± 23.4 μg/kg/min) (P < 0.001). There was no statistically significant difference in the time to awake between the two groups. The incidence of artificial airway interventions and hypotension in the PRO group (36%, 60%) were significantly higher than those in the DEX group (4.2%, 16.7%) (P = 0.011, P = 0.003, respectively). In addition, the occurrence of bradycardia increased significantly in the DEX group (58.3%) compared with the PRO group (12%) (P < 0.001).

Conclusions
The single loading dose of dexmedetomidine combined with propofol can reduce propofol consumption and artificial airway intervention and provide better hemodynamic stability than propofol for deep sedation in elderly patients during ERCP.

Trial registration
www.chictr.org.cn (Registration number ChiCTR1900028069, Registration date 10/12/2019).
Predictive performances of ALS and BLS termination of resuscitation rules in out-of-hospital cardiac arrest for different resuscitation protocols
Authors: Lin Yu-Yuan , Lai Yin-Yu , Chang Hung-Chieh , Lu Chien-Hsin , Chiu Po-Wei , Kuo Yuh-Shin , Huang Shao-Peng , Chang Ying-Hsin , Lin Chih-Hao 
Published: March 2022

Abstract
Background
Resuscitation guidance has advanced; however, the predictive performance of the termination of resuscitation (TOR) rule has not been validated for different resuscitation protocols published by the American Heart Association (AHA).

Methods
A retrospective study validating the basic life support (BLS) and advanced life support (ALS) TOR rules was conducted using an Utstein-style database in Tainan city, Taiwan. Adult patients with nontraumatic out-of-hospital cardiac arrests from January 1, 2015, to December 31, 2015, (using the AHA 2010 resuscitation protocol) and from January 1, 2020, to December 31, 2020, (using the AHA 2015 resuscitation protocol) were included. The characteristics of rule performance were calculated, including sensitivity, specificity, positive predictive value (PPV) and negative predictive value.

Results
Among 1260 eligible OHCA patients in 2015, 757 met the BLS TOR rule and 124 met the ALS TOR rule. The specificity and PPV for predicting unfavorable neurological outcomes were 61.1% and 99.0%, respectively, for the BLS TOR rule and 93.8% and 99.2%, respectively, for the ALS TOR rule. A total of 970 OHCA patients were enrolled in 2020, of whom 438 met the BLS TOR rule and 104 met the ALS TOR rule. The specificity and PPV for predicting unfavorable neurological outcomes were 85.7% and 100%, respectively, for the BLS TOR rule and 99.5% and 100%, respectively, for the ALS TOR rule.

Conclusions
Both the BLS and ALS TOR rules performed better when using the 2015 AHA resuscitation protocols compared to the 2010 protocols, with increased PPVs and decreased false-positive rates in predicting survival to discharge and good neurological outcomes at discharge. The BLS and ALS TOR rules can perform differently while the resuscitation protocols are updated. As the concepts and practices of resuscitation progress, the BLS and ALS TOR rules should be evaluated and validated accordingly.
“This path I must walk alone”. Challenges experienced by older patients while recovering from severe COVID-19 – a qualitative study
Authors: Heiberg Kristi Elisabeth , Jøranson Nina , Heggestad Anne Kari Tolo , Breievne Grete , Lausund Hilde , Myrstad Marius , Ranhoff Anette Hylen , Walle-Hansen Marte Meyer , Bruun-Olsen Vigdis 
Published: March 2022

Abstract
Background
In March 2020, the COVID-19 pandemic challenged both the Norwegian population and healthcare system. In this study we explored how older men and women experienced rehabilitation and recovery after hospitalisation due to severe COVID-19.

Methods
Semi-structured interviews with 17 participants aged 60–96 years were performed 6 months after discharge from hospital. A thematic descriptive analysis was conducted.

Results
The results revealed that the participants experienced a challenging span between loneliness and companionship in recovering from severe COVID-19. The four subthemes highlighted experiences of being discharged to home and left to themselves, the importance of exercise and companionship at rehabilitation stay, requirement of self-effort and time to recover, and the challenging span between loneliness and companionship when being with family.

Conclusion
Among participants, the experiences of loneliness throughout the recovery period were striking. An individualised approach including psychological support should be emphasized in primary healthcare to promote recovery in older survivors after severe COVID-19 and their next-of-kin.
Applying the behaviour change wheel to develop a smartphone application ‘stay-active’ to increase physical activity in women with gestational diabetes
Authors: Smith R. , Michalopoulou M. , Reid H. , Riches S. Payne , Wango Y. N. , Kenworthy Y. , Roman C. , Santos M. , Hirst J. E. , Mackillop L. 
Published: March 2022

AbstractBackgroundPhysical activity (PA) interventions are an important but underutilised component in the management of gestational diabetes mellitus (GDM). The challenge remains how to deliver cost effective PA interventions that have impact on individual behaviour. Digital technologies can support and promote PA remotely at scale. We describe the development of a behaviourally informed smartphone application (Stay-Active) for women attending an NHS GDM clinic. Stay-Active will support an existing motivational interviewing intervention to increase and maintain PA in this population.MethodsThe behaviour change wheel (BCW) eight step theoretical approach was used to design the application. It provided a systematic approach to understanding the target behaviour, identifying relevant intervention functions, and specifying intervention content. The target behaviour was to increase and maintain PA. To obtain a behavioural diagnosis, qualitative evidence was combined with focus groups on the barriers and facilitators to PA in women with GDM. The findings were mapped onto the Capability Opportunity Motivation-Behaviour (COM-B) model and Theoretical Domains Framework to identify what needs to change for the target behaviour and linked to appropriate intervention functions. Finally, behaviour changes techniques (BCT) and modes of delivery that are most likely to serve the intervention functions were selected. Current evidence, patient focus groups and input from key stakeholders informed Stay-Active’s development.ResultsWe found that psychological capability, reflective and automatic motivation, social and physical opportunity needed to change to increase PA in women with GDM. The four key intervention functions identified were Enablement, Education, Persuasion and Training. Stay-Active incorporates these four intervention functions delivering ten BCTs including: goal setting, credible source, self-monitoring, action planning, prompts and cues. The final design of Stay-Active delivers these BCTs via an educational resource centre, with goal setting and action planning features, personalised performance feedback and individualised promotional messages.ConclusionThe BCW has enabled the systematic and comprehensive development of Stay-Active to promote PA in women with GDM within an NHS Maternity service. The next phase is to conduct a trial to assess the feasibility and acceptability of a multi-component intervention that combines Stay-Active with PA Motivational Interviewing.
Can cell salvage be used for resuscitation in a patient with amniotic fluid embolism and hepatic laceration? A case report
Authors: Li Ping , Luo Linli , Luo Dong , Wang Rurong 
Published: March 2022

Abstract
Background
Amniotic fluid embolism (AFE) is a rare disease that can lead to profound coagulopathy and hemorrhage, especially when combined with the laceration and bleeding of other organs. Intraoperative cell salvage (ICS) has been widely used for treating obstetric hemorrhage, but it remains unclear whether ICS can be used in the treatment of AFE.

Case presentation
We report the case of a 27-year-old woman at 39 weeks’ gestation who suddenly developed severe abdominal pain, convulsions, loss of consciousness, and decreased vital signs during labor. Despite an emergency cesarean section being performed, the parturient experienced sudden cardiac arrest. Fortunately, the heart rate spontaneously recovered after effective cardiopulmonary resuscitation (CPR). Further abdominal exploration revealed right hepatic laceration with active bleeding. ICS was performed and the salvaged blood was promptly transfused back to the patient. Subsequently, the patient was diagnosed with AFE based on hypotension, hypoxia, coagulopathy, and cardiac arrest. The patient was transfused with 2899 mL salvaged blood during surgery with no adverse effects. At 60- and 90-day follow-ups, no complaints of discomfort or abnormal laboratory test results were observed in the mother or the baby.

Conclusion
ICS was used to rescue patient with AFE, and ICS did not worsen the condition of patients with AFE. For pregnant women who received CPR, clinicians should explore the presence of hepatic laceration which can be fatal to patients.
Prognostic variables for conditional survival in patients with esophageal squamous cell carcinoma who underwent minimally invasive surgery
Authors: Liang Mingqiang , Xiao Jiazhou , Chen Maohui , Zheng Bin , Chen Chun 
Published: March 2022

Abstract
Background
Esophageal squamous cell carcinoma (ESCC) survival is mainly reported at the time of treatment. Conditional survival is another prognostic tool to evaluate ESCC patients who has survived more than one year since treatment.

Methods
We analyzed data from 705 ESCC patients who underwent minimally invasive surgery between 2013 and 2016. Using the Kaplan–Meier method, we computed a 5-year relative conditional survival. We also investigated the prognostic factors associated with survival using Cox proportional hazards models.

Results
Conditional survival improved over time for all cohorts of ESCC patients who survived a period after surgery. The greatest improve in conditional survival were observed in patients 2 years after surgery. In addition, the results of the Cox survival model from the time of surgery, T stage (p < 0.001), N stage (p < 0.001), and anastomotic leak (p = 0.022), were significantly associated with survival. However, the results of the Cox survival model from 2 years after surgery, N stage (p < 0.001), and anastomotic leak (p = 0.032) were significantly associated with survival.

Conclusion
For ESCC patients who survived a period after surgery, the largest increases in conditional survival were observed in patients 2 years after surgery. We suggest that patients with anastomotic leakage and higher T and N stages should be strictly screened according to various time, and that conditional survival should be used as a powerful prognostic tool for ESCC patients.
Vernal keratoconjunctivitis with a limbal mass lesion developing independently of severe papillae formation at the tarsal conjunctiva: a case report
Authors: Shinji Koichiro , Chikama Taiichiro , Masuda Shun , Arihiro Koji , Kiuchi Yoshiaki 
Published: March 2022

Abstract
Background
A hypertrophic limbal mass lesion is an uncommon finding of vernal keratoconjunctivitis; it normally occurs in eyes with severe papillae formation in the tarsal conjunctiva. We present a case with a limbal mass lesion in a patient with relatively mild allergic findings in the tarsal conjunctiva.

Case presentation
A 12-year-old Japanese boy displaying allergic conjunctivitis presented with a mass lesion at the inferior limbus in the left eye. Relatively mild papillae formation was found on the tarsal conjunctiva in both eyes. We diagnosed that the mass lesion resulted from limbal vernal keratoconjunctivitis and resected it for therapeutic purposes. Histopathological examination showed that eosinophils, lymphocytes, and fibroblasts were present in the subepithelial lesion and the substantia propria of the mass lesion. Immunohistochemical staining detected diffuse and rich infiltration of CD3-positive T lymphocytes and a relatively small number of CD20-positive B lymphocytes and CD138-positive plasma cells that tended to aggregate. The histopathologic features suggested that the limbal mass lesion had similar structures to the papillae at the tarsal conjunctiva of vernal keratoconjunctivitis.

Conclusion
The limbal mass lesion as a finding of vernal keratoconjunctivitis can occur even if the papillae formation at the patient’s tarsal conjunctiva is mild.
Considering intermittent fasting among Saudis: insights into practices
Authors: Alnasser Aroub , Almutairi Mashael 
Published: March 2022

Abstract
Background
There is a dearth of studies on intermittent fasting in Saudi Arabia outside of Ramadan. The aim of this research was to study and describe the practice of intermittent fasting outside of Ramadan among Saudi people.

Methods
A web-based survey that focused on intermittent fasting practices—specifically the use of intermittent fasting applications, goal setting, and the effects of fasting on an individual’s state of health—was administered, collected, and analyzed.

Results
The study revealed that 58% (298/514) of the respondents practiced intermittent fasting for a duration of less than 3 months. The most-practiced pattern of intermittent fasting was a 16/8 fasting pattern (43.8%, 225/514). About 88.3% (454/514) of those who followed intermittent fasting drank fluids while fasting. Additionally, the amount of weight loss after intermittent fasting was less than 2.2 kg for 35% (180/514) of the participants. The primary goal of intermittent fasting for 44.9% (231/514) of the respondents was to lose weight. The majority of the participants (84.6%, 435/514) did not use any fasting applications.

Conclusion
The results of the current research on intermittent fasting outside of Ramadan are preliminary and inconclusive. The findings of the present study advance the idea that for some Saudis, the practice of intermittent fasting does not necessarily begin and end with Ramadan; this finding may present a strategic opportunity for Saudi health professionals who are focused on the obesity epidemic and other public health issues in Saudi Arabia. This study sought to help start a discussion on this topic and fill the knowledge gap.
'Toothless’—the absence of political priority for oral health: a case study of Ireland 1994–2021
Authors: McAuliffe Úna , Whelton Helen , Harding Máiréad , Burke Sara 
Published: March 2022

Abstract
Background
Calls are emerging for oral health system reform under the Universal Healthcare (UHC) domain, while internationally there is an absence of political priority for oral health. In the Republic of Ireland there is very limited coverage of oral healthcare for the whole population. ‘Smile agus Sláinte’ Ireland’s oral health policy published in 2019, represents the first change to national policy in over 25 years.

Methods
This research examined the key factors influencing oral health policy, development, and implementation in Ireland during the period 1994–2021. A case study approach was adopted with two strands of data collection: documentary analysis and semi-structured interviews with elite participants. Analysis was guided by Howlett’s five stream framework.

Results
Ireland shares the international experience of oral health having very low political priority. This has perpetuated unequal access to public dental services for children and special needs populations while austerity measures applied to adult schemes resulted in increased unmet need with no universal coverage for dental care. The only area where there is political interest in oral health is orthodontic care. This low political priority combined with a lack of actor power in national leadership positions in the Department of Health and Health Service Executive has contributed to successive non-implementation of oral health policy recommendations. This is most evident in the failure to publish the Draft National Oral Health Policy in 2009. The research finds a failure to adequately engage with key stakeholders, particularly the dental profession in the development of the 2019 policy. All these weaknesses have been exacerbated by the COVID-19 pandemic.

Conclusions
Ireland’s new oral health policy, ‘Smile agus Sláinte’, presents an opportunity for the provision of much needed public dental services. However, successful reform will require strong political will and collaboration with dental leadership to provide advocacy at national level. Global calls to incorporate oral health into the UHC agenda and an agreed political consensus for UHC in Ireland may provide an opportunity for change. Genuine engagement of all stakeholders to develop an implementation strategy is necessary to harness this potential window of opportunity for oral health system reform.