bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of various breath‐hold techniques on the cardiorespiratory response to facial immersion in humans
Authors: Burley Matthew J. , Blackwell Jamie , Bond Bert , Williams Craig , Stephens Francis B. 
Published: November 2022

AbstractRepeated maximal breath‐holds have been demonstrated to induce bradycardia, increase haematocrit and haemoglobin and prolong subsequent breath‐hold duration by 20%. Freedivers use non‐maximal breath‐hold techniques (BHTs) to improve breath‐hold duration. The aim of this study was to investigate the cardiorespiratory and haematological responses to various BHTs. Ten healthy men (34.5 ± 1.9 years) attended five randomized experimental trials and performed a 40 min period of quiet rest or one of three BHTs followed by a maximal breath‐hold challenge during facial immersion in water at 30 or 10°C. Cardiovascular and respiratory parameters were measured continuously using finger plethysmography and breath‐by‐breath gas analysis, respectively, and venous blood samples were collected throughout. Facial immersion in cold water caused marked bradycardia (74.1 vs. 50.2 beats/min after 40 s) but did not increase breath‐hold duration compared with warm water control conditions. Facial immersion breath‐hold duration was 30.8–43.3% greater than the control duration when preceded by BHTs that involved repeated breath‐holds of constant duration (P = 0.021), increasing duration (P < 0.001) or increasing frequency (P < 0.001), with no difference observed between BHTs. The increased duration of apnoea across all three BHT protocols was associated with a 6.8% increase in end‐tidal O2 and a 13.1% decrease in end‐tidal CO2 immediately before facial immersion. There were no differences in blood pressure, cardiac output, heart rate, haematocrit or haemoglobin between each BHT and control conditions (P > 0.05). In conclusion, the duration of apnoea can be extended by manipulating blood gases through repeated prior breath‐holds, but changes in cardiac output and red blood cell mass do not appear essential.
Gene editing of human iPSCs rescues thrombophilia in hereditary antithrombin deficiency in mice
Authors: Tang Liang V. , Tao Yanyi , Feng Yuanzheng , Ma Jiewen , Lin Wenyi , Zhang Yuyang , Zhang Yi , Wu Tingting , Cai Yaohua , Lu Hui , Wei Jun , Corral Javier , Hu Yu 
Published: November 2022

Hereditary antithrombin deficiency is caused by
SERPINC1
gene mutations and predisposes to recurrent venous thromboembolism that can be life-threatening. Therefore, lifelong anticoagulation is required, which has side effects and may not be effective. In this study, peripheral blood mononuclear cells from a patient with severe antithrombin deficiency were reprogrammed into induced pluripotent stem cells (iPSCs). The mutation was corrected using CRISPR-Cas9 and Cre/LoxP genome editing. iPSCs were differentiated into hepatocytes, which were injected into the spleen of antithrombin knockout mice to restore the activity of antithrombin and reduce the thrombophilic state. Human iPSC-differentiated hepatocytes colonized mice and secreted antithrombin stably, normalizing antithrombin in plasma (activity: from 46.8 ± 5.7% to 88.6 ± 7.6%,
P
< 0.0001; antigen: from 146.9 ± 19.5 nanograms per milliliter to 390.7 ± 16.1 nanograms per milliliter,
P
< 0.0001). In venous thrombosis model, the rate of thrombosis in mice treated with edited hepatocytes, parental hepatocytes, and wild-type mice were 60, 90, and 70%, respectively. The thrombus weight was much lighter in mice treated with edited hepatocytes compared with parental hepatocytes (7.25 ± 2.00 milligrams versus 15.32 ± 2.87 milligrams,
P
= 0.0025) and showed no notable difference compared with that in wild-type mice (10.41 ± 2.91 milligrams). The activity and concentration of antithrombin remained high for 3 weeks after injection. The liver and kidney function markers showed no obvious abnormality during the observation period. This study provides a proof of principle for correction of mutations in patient-derived iPSCs and potential therapeutic applications for hereditary thrombophilia.
Effect of sport on health in people aged 60 years and older: a systematic review with meta-analysis
Authors: S Oliveira Juliana , Gilbert Stephen , Pinheiro Marina B , Tiedemann Anne , Macedo Liane Brito , Maia Laísa , Kwok Wing , Hassett Leanne , Sherrington Catherine 
Published: November 2022

ObjectivesTo summarise evidence of benefits of sport for health among people aged 60+.DesignSystematic review with meta-analysis of randomised controlled trials (RCTs).Data sourcesMedline, CINAHL, SPORTDiscus, the Physiotherapy Evidence Database from inception to April 2021.Study selectionRCTs investigating the effect of sport on health-related outcomes in people aged 60+ compared with non-active control.Data synthesis and analysisPooled effect sizes were calculated using random-effect models. Standardised mean differences (SMD), and mean difference (MD) were calculated. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the certainty of the evidence for analyses with ≥3 studies.ResultsNine trials (628 participants) reported in 15 articles were included. Participation in sport improved cardiorespiratory fitness (n=5 trials; SMD=0.43, 95% CI 0.17 to 0.70; low certainty evidence), physical function (n=4; SMD=0.62, 95% CI 0.05 to 1.18; very low certainty evidence), and mental health (n=2; SMD=0.28, 95% CI 0.06 to 0.51) and reduced fat mass (n=6; MD=−0.99 kg, 95% CI −1.75kg to −0.23 kg; low certainty evidence) among older people. We found no significant effects of sport on overall physical activity participation, strength, balance, lean mass and bone mineral density (BMD). One study investigating quality of life reported a positive, but non-significant effect of sport.ConclusionSport may have a positive impact on health outcomes in people aged 60+. There was uncertainty on the effect of sport on strength, balance, lean mass and BMD. Further research is needed to investigate the optimal type and dose of sport to maximise the long-term benefits among older people.
Preventing chronic disease in overweight and obese patients with low health literacy using eHealth and teamwork in primary healthcare (HeLP-GP): a cluster randomised controlled trial
Authors: Parker Sharon M , Barr Margo , Stocks Nigel , Denney-Wilson Elizabeth , Zwar Nicholas , Karnon Jon , Kabir Alamgir , Nutbeam Don , Roseleur Jackie , Liaw Siaw-Teng , McNamara Carmel , Frank Oliver , Tran An , Osborne Richard , Lau Annie Y S , Harris Mark 
Published: November 2022

ObjectivesTo evaluate a multifaceted intervention on diet, physical activity and health literacy of overweight and obese patients attending primary care.DesignA pragmatic two-arm cluster randomised controlled trial.SettingUrban general practices in lower socioeconomic areas in Sydney and Adelaide.ParticipantsWe aimed to recruit 800 patients in each arm. Baseline assessment was completed by 215 patients (120 intervention and 95 control).InterventionA practice nurse-led preventive health check, a mobile application and telephone coaching.Primary and secondary outcome measuresPrimary outcomes were measured at baseline, 6 and 12 months, and included patient health and eHealth literacy, weight, waist circumference and blood pressure. Secondary outcomes included changes in diet and physical activity, preventive advice and referral, blood lipids, quality of life and costs. Univariate and multivariate analyses of difference-in-differences (DiD) estimates for each outcome were conducted.ResultsAt 6 months, the intervention group, compared with the control group, demonstrated a greater increase in Health Literacy Questionnaire domain 8 score (ability to find good health information; mean DiD 0.22; 95% CI 0.01 to 0.44). There were similar differences for domain 9 score (understanding health information well enough to know what to do) among patients below the median at baseline. Differences were reduced and non-statistically significant at 12 months. There was a small improvement in diet scores at 6 months (DiD 0.98 (0.50 to 1.47); p=0.026) but not at 12 months. There were no differences in eHealth literacy, physical activity scores, body mass index, weight, waist circumference or blood pressure.ConclusionsTargeted recruitment and engagement were challenging in this population. While the intervention was associated with some improvements in health literacy and diet, substantial differences in other outcomes were not observed. More intensive interventions and using codesign strategies to engage the practices earlier may produce a different result. Codesign may also be valuable when targeting lower socioeconomic populations.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN 12617001508369) (http://www.ANZCTR.org.au/ACTRN12617001508369.aspx).Trial protocolThe protocol for this trial has been published (open access;https://bmjopen.bmj.com/content/8/6/e023239).
Trends in the prevalence of metabolically healthy and unhealthy obesity in the US adult population: analysis of eight NHANES cross-sectional survey cycles, 1999–2014
Authors: Wen Yue , Liu Tingting , Li Shengxu , Gong Renrong , Li Changwei 
Published: November 2022

ObjectiveTo exam the time trend of the prevalence of metabolically healthy obesity (MHO) in the US adult population.DesignEight cross-sectional survey cycles.SettingNational Health and Nutrition Examination Survey (NHANES), 1999–2014.Participants16 459 NHANES participants aged 20 years and older.Primary outcome measureMHO was defined as central obesity (waist circumference ≥102 cm for men and ≥88 cm for women) without any of the following conditions: elevated levels of blood pressure (≥130/85 mm Hg), glucose (≥100 mg/dL) and triglycerides (≥150 mm/dL); reduced levels of high-density lipoprotein cholesterol (<40 mg/dL for men and <50 mg/dL for women) or any medication use for high cholesterol, hypertension or diabetes.ResultsThe prevalence of central obesity significantly increased from 45.2% in 1999–2000 to 56.7% in 2013–2014 (p=0.003). Over the same period, MHO prevalence among those with central obesity only slightly and non-significantly increased from 11.0% to 15.7% (p=0.38). However, MHO prevalence among women increased significantly (p=0.04) from 7.1% to 13.7%. Female gender, a younger age, being Hispanic and non-Hispanic black and high education (some college or above) were significantly (p<0.05) associated with higher prevalence of MHO.ConclusionsWhile the prevalence of central obesity in the US population has increased since 1999, the prevalence of MHO among those who are centrally obese remained fairly stable.
Prevalence of malnutrition among old people in Africa: systematic review and meta-analysis
Authors: Seid Ahmed Muhye , Fentahun Netsanet 
Published: November 2022

ObjectiveTo summarise available evidence and estimate the pooled prevalence of malnutrition among old people in Africa.DesignSystematic review and meta-analysis.SettingAny healthcare or community research reporting the prevalence or incidence of malnutrition in Africa from January 2000 to October 2021.ParticipantsOld people, aged above 60 years.Outcome measuresMalnutrition, either undernutrition or overnutrition.ResultsA total of 1442 studies were retrieved based on the search strategy, where only 36 studies (n=15 266 participants) reported from 11 African countries were included for meta-analysis. The reported prevalence of malnutrition ranges from 2.2% to 77.3% across the continent. Overall, the pooled prevalence rates of undernutrition and overnutrition were 18% (95% CI: 15% to 22%; I2=98.1; p<0.001) and 33% (95% CI: 22% to 44%; p<0. 001), respectively.ConclusionThe prevalence of malnutrition in old African people is high and differs by setting, assessment tool and country of residence. Hence, due attention to geriatric nutrition is mandatory, and the need for a valid, reliable and simple screening tool should be thought of.
Experiences of medical and dental students of Pakistan during COVID-19 pandemic lockdown: a qualitative study
Authors: Iftikhar Sundus , Saleem Sarosh , Aziz Iqra , Sana Momal 
Published: November 2022

ObjectiveThe COVID-19 pandemic resulted in medical institutes being shut down. Face-to-face activities were shifted to online medium. The unpredictability of the situation impacted medical faculty and students alike, creating panic and anxiety. Since these students are to take hold of the healthcare system of the country soon, it is important to learn their perspective on how COVID impacted them. Therefore, this study aimed to explore the lived experiences of Pakistani medical students in-depth by a qualitative observation of their personal and educational experiences.DesignA phenomenological qualitative study interviewing medical students of Pakistan was conducted.Participants/MethodologyThis study was designed to interview medical and dental students from various cities in Pakistan using a semistructured, open-ended questionnaire. A total of 34 interviews were recorded and transcripts were prepared. All authors (SI, SS, IA and MS) were involved in the thematic analysis of the data, whereby transcripts were read thoroughly, and codes were developed. Similar codes were then combined to generate themes.ResultsThree major themes emerged after the analysis of results. The students’ ‘diverse experiences’ of panic and anxiety or excitement were high initially but gradually reduced as time progressed. The ‘unprecedented academic experiences’ of students included teaching/learning, communication and technical challenges that they faced during online classes. Despite facing a lot of challenges, the students still saw ‘light at the end of the tunnel’ and looked forward to going back to their college.ConclusionThe effects of COVID on the physical, psychological, social and academic life of medical students were enormous. It is highly recommended that institutes and faculty provide support for personal and professional development of students in these unprecedented times in the form of counselling, provision of technical facilities or leniency in fee process. Peer support is also considered crucial in reducing anxiety among students.
Interactive effects of meteorological factors and air pollutants on hand, foot, and mouth disease in Chengdu, China: a time-series study
Authors: Huang Jiaqi , Ma Yue , Lv Qiang , Liu Yaqiong , Zhang Tao , Yin Fei , Shui Tiejun 
Published: November 2022

ObjectivesHand, foot, and mouth disease (HFMD) is a viral infectious disease that poses a substantial threat in the Asia-Pacific region. It is widely reported that meteorological factors are associated with HFMD. However, the relationships between air pollutants and HFMD are still controversial. In addition, the interactive effects between meteorological factors and air pollutants on HFMD remain unknown. To fill this research gap, we conducted a time-series study.DesignA time-series study.Setting and participantsDaily cases of HFMD as well as meteorological and air pollution data were collected in Chengdu from 2011 to 2017. A total of 184 610 HFMD cases under the age of 15 were included in our study.Outcome measuresDistributed lag nonlinear models were used to investigate the relationships between HFMD and environmental factors, including mean temperature, relative humidity, SO2, NO2, and PM10. Then, the relative excess risk due to interaction (RERI) and the proportion attributable to interaction were calculated to quantitatively evaluate the interactions between meteorological factors and air pollutants on HFMD. Bivariate response surface models were used to visually display the interactive effects.ResultsThe cumulative exposure–response curves of SO2and NO2were inverted ‘V’-shaped and ‘M’-shaped, respectively, and the risk of HFMD gradually decreased with increasing PM10concentrations. We found that there were synergistic interactions between mean temperature and SO2, relative humidity and SO2, as well as relative humidity and PM10on HFMD, with individualRERIs of 0.334 (95% CI 0.119 to 0.548), 0.428 (95% CI 0.214 to 0.642) and 0.501 (95% CI 0.262 to 0.741), respectively, indicating that the effects of SO2and PM10on HFMD were stronger under high temperature (>17.3°C) or high humidity (>80.0%) conditions.ConclusionsThere were interactive effects between meteorological factors and air pollutants on HFMD. Our findings could provide guidance for targeted and timely preventive and control measures for HFMD.
Isoformic PD-1-mediated immunosuppression underlies resistance to PD-1 blockade in hepatocellular carcinoma patients
Authors: Tan Zhiwu , Chiu Mei Sum , Yang Xinxiang , Yue Ming , Cheung Tan To , Zhou Dongyan , Wang Yuewen , Chan Anthony Wing-Hung , Yan Chi Wing , Kwan Ka Yi , Wong Yik Chun , Li Xin , Zhou Jingying , To Ka Fai , Zhu Jiye , Lo Chung Mau , Cheng Alfred Sze-Lok , Chan Stephen Lam , Liu Li , Song You-Qiang , Man Kwan , Chen Zhiwei 
Published: November 2022

ObjectiveImmune checkpoint blockade (ICB) has improved cancer treatment, yet why most hepatocellular carcinoma (HCC) patients are resistant to PD-1 ICB remains elusive. Here, we elucidated the role of a programmed cell death protein 1 (PD-1) isoform, Δ42PD-1, in HCC progression and resistance to nivolumab ICB.DesignWe investigated 74 HCC patients in three cohorts, including 41 untreated, 28 treated with nivolumab and 5 treated with pembrolizumab. Peripheral blood mononuclear cells from blood samples and tumour infiltrating lymphocytes from tumour tissues were isolated for immunophenotyping. The functional significance of Δ42PD-1 was explored by single-cell RNA sequencing analysis and validated by functional and mechanistic studies. The immunotherapeutic efficacy of Δ42PD-1 monoclonal antibody was determined in HCC humanised mouse models.ResultsWe found distinct T cell subsets, which did not express PD-1 but expressed its isoform Δ42PD-1, accounting for up to 71% of cytotoxic T lymphocytes in untreated HCC patients. Δ42PD-1+T cells were tumour-infiltrating and correlated positively with HCC severity. Moreover, they were more exhausted than PD-1+T cells by single T cell and functional analysis. HCC patients treated with anti-PD-1 ICB showed effective PD-1 blockade but increased frequencies of Δ42PD-1+T cells over time especially in patients with progressive disease. Tumour-infiltrated Δ42PD-1+T cells likely sustained HCC through toll-like receptors-4-signalling for tumourigenesis. Anti-Δ42PD-1 antibody, but not nivolumab, inhibited tumour growth in three murine HCC models.ConclusionOur findings not only revealed a mechanism underlying resistance to PD-1 ICB but also identified anti-Δ42PD-1 antibody for HCC immunotherapy.
Cryotherapy for oral mucositis in cancer: review of systematic reviews and meta-analysis
Authors: Amiri Khosroshahi Reza , Talebi Sepide , Travica Nikolaj , Mohammadi Hamed 
Published: November 2022

BackgroundOne of the most common side effects of cancer treatment is oral mucositis. Although studies have shown that oral cryotherapy has a favourable effect on oral mucositis, the reliability of the results is questionable.ObjectiveThe goal of this umbrella review was to provide insight into the effects of oral cryotherapy against oral mucositis in patients with cancer, as well as to assess the certainty of this evidence.MethodStudies were searched for through PubMed, Scopus and Web of Science, with no restrictions until August 2021. The risk ratio (RR) and 95% CI for each meta-analysis were recalculated using a random-effects model, and the certainty of the evidence was judged using Grading of Recommendations Assessment, Development and Evaluation.ResultsTen meta-analyses including 25 original RCTs that fit our inclusion criteria were included. The use of oral cryotherapy markedly reduced the occurrence of overall (RR 0.72, 95% CI 0.64 to 0.83, n=20 trials), moderate to severe (RR 0.60, 95% CI 0.45 to 0.80, n=16 trials) and severe oral mucositis (RR 0.48, 95% CI 0.34 to 0.67, n=16 trials), as well as average severity score of oral mucositis (standardised mean difference=−0.94, 95% CI −1.28 to −0.59, n=4 trials) in comparison to a control group; however, the certainty of evidence for all outcomes was rated very low.ConclusionIn patients with cancer, oral cryotherapy appears to greatly lower the severity and occurrence of oral mucositis, but, with very low certainty of evidence.
Ordovician of the conterminous United States
Authors: McLaughlin Patrick I. , Stigall Alycia L. 
Published: November 2022

Abstract
The Ordovician rocks of the conterminous United States (US) have a complex history, spanning multiple ancient basins, shifting palaeoclimate and evolving tectonic regimes. The US portion of the palaeocontinent of Laurentia occupied a relatively stable and isolated position around the southern tropics during the Ordovician. In general, Lower Ordovician rocks form a vast autochthonous blanket of fine-grained (tropical) carbonates that covered much of Laurentia, named the ‘Great American Carbonate Bank’. Outboard, ribbon carbonates and graptolitic shales are found in allochthonous fragments of the ancient continental margin. Middle Ordovician strata are more lithologically diverse, including the addition of several regionally distributed sandstones of the inner detrital belt, mostly overlying the Sauk–Tippecanoe unconformity. Upper Ordovician strata show the greatest lithologic and faunal diversity, reflecting steepening topography resulting from regional compression along the south Laurentian (Appalachian) margin. Recent advances in the interpretation of the US Ordovician come primarily from studies of carbon and oxygen stable isotopes, sequence stratigraphy, palaeoecology, tephrochronology, redox geochemistry, strontium isotopes and geochronology.
Instance Space Analysis for Algorithm Testing: Methodology and Software Tools
Authors: Smith-Miles Kate , Muñoz Mario Andrés 
Published: November 2022

Instance Space Analysis (ISA) is a recently developed methodology to (a) support objective testing of algorithms and (b) assess the diversity of test instances. Representing test instances as feature vectors, the ISA methodology extends Rice’s 1976 Algorithm Selection Problem framework to enable visualization of the entire space of possible test instances, and gain insights into how algorithm performance is affected by instance properties. Rather than reporting algorithm performance on average across a chosen set of test problems, as is standard practice, the ISA methodology offers a more nuanced understanding of the unique strengths and weaknesses of algorithms across different regions of the instance space that may otherwise be hidden on average. It also facilitates objective assessment of any bias in the chosen test instances and provides guidance about the adequacy of benchmark test suites. This article is a comprehensive tutorial on the ISA methodology that has been evolving over several years, and includes details of all algorithms and software tools that are enabling its worldwide adoption in many disciplines. A case study comparing algorithms for university timetabling is presented to illustrate the methodology and tools.