bluuebunny/crossref_metadata_2025 huggingface dataset:
The micrometeorite flux in the Albian–Aptian age (ca. 103–117 Ma): A search for Tycho ejecta in pelagic sediments using chrome spinels
Authors: Martin* Ellinor , Schmitz Birger , Terfelt Fredrik , Aguirre-Palafox Luis Erick , Alvarez Walter
Published: March 2022

Numerical models of meteorite delivery from impacts on the Moon have demonstrated that the impact event forming the lunar crater Tycho (~85 km diameter; ca. 109 Ma age) would have delivered considerable amounts of ejected material to Earth. The ejecta, containing lunar Ti- and V-rich chrome spinels, would have been distributed globally and admixed with seafloor sediments over a few meters of a typical marine stratigraphic interval. In order to locate such ejecta, samples weighing ~12–25 kg each, with one-meter spacing were extracted over an ~30 m interval of the deep-sea formed Calera Limestone, Albian and Aptian age (ca. 103–117 Ma), from the Pacifica Quarry, south of San Francisco. The limestone samples were leached in acids and residues searched for possible lunar Ti-rich chrome-spinel grains.

In a total of 689 kg of limestone, 1154 chrome-spinel grains were found. Of these, 319 contain >0.45 wt% V2O3, of which 227 originate from equilibrated ordinary chondrites. The majority of the other 92 grains with >0.45 wt% V2O3 are most likely from different types of achondritic meteorites. Among these, we found eleven particularly Ti-rich chrome-spinel grains. The elemental abundances of these grains were compared with chrome spinel from lunar, howardite-eucrite-diogenite (HED) and R-chondritic meteorites. This showed that only one of these grains could potentially be of lunar origin. The bulk of the other grains likely originate from HED meteorites based on oxygen isotopic analysis of similar grains in previous studies. Grains with TiO2 >10 wt%, common among lunar spinels are not found, further supporting an HED source for the Ti-rich grains. In summary, Albian and Aptian strata in the Pacifica quarry do not likely record any major lunar impact event. Either the timing of the impact is located within a ca. 110–114 Ma unconformity in the middle part of the section or the impact is likely older than the interval searched.
Pre-diabetes, diabetes and fluctuations of glucose tolerance after gestational diabetes mellitus: 5-year follow-up of a contemporary, prospective study in Germany
Authors: Haschka Stefanie J , Gar Christina , Sacco Vanessa , Banning Friederike , Ferrari Uta , Freibothe Ines , Kern-Matschilles Stefanie , Potzel Anne L , Rauch Barbara , Fueessl Louise U , Meisel Mandy , Benz Irina , Then Cornelia , Seissler Jochen , Lechner Andreas
Published: March 2022

Introduction

Ten years ago, Germany started offering screening for gestational diabetes mellitus (GDM) to all pregnant women. This approach revealed more but also, on average, less severe cases of GDM than the risk-based screening practiced previously. We now examined the incidence of pre-diabetes and diabetes following a GDM diagnosis in the era of universal screening in Germany and compared our results with studies in the previous period. Additionally, we examined the year-to-year fluctuations of glucose tolerance after a pregnancy complicated by GDM.

Research design and methods

We report 5-year follow-up data from 202 women in the prospective, monocenter, postpartum study PPSDiab. Consecutive recruitment took place in Munich, Germany between 2011 and 2016. In the study, we conducted yearly examinations that included anthropometrics, laboratory chemistry and oral glucose tolerance testing.

Results

During the first 5 years post partum, 111 (55%) and 12 (6%) of the women developed pre-diabetes and type 2 diabetes, respectively, while 2 (1%) developed type 1 diabetes. Impaired fasting glucose (IFG) was the most common first manifestation of disturbed glucose tolerance, followed by impaired glucose tolerance (IGT), the combination of IFG and IGT, and diabetes. Glucose tolerance did not deteriorate steadily in most women but fluctuated from year to year.

Conclusions

In our analysis, the incidence of diabetes, both type 1 and type 2, after GDM diagnosed in universal screening was substantially lower than in studies from the previous period of risk-based screening. Nevertheless, the high incidence of pre-diabetes we observed after GDM still confirms the importance of this diagnosis as a risk marker. Additionally, we documented frequent fluctuations of glucose tolerance from 1 year to the next. Therefore, a single postpartum glucose tolerance test, as currently practiced in routine care, may be insufficient for reliable risk stratification after GDM.
Towards the elimination of cervical cancer in low-income and lower-middle-income countries: modelled evaluation of the effectiveness and cost-effectiveness of point-of-care HPV self-collected screening and treatment in Papua New Guinea
Authors: Nguyen Diep Thi Ngoc , Simms Kate T , Keane Adam , Mola Glen , Bolnga John Walpe , Kuk Joseph , Toliman Pamela J , Badman Steven G , Saville Marion , Kaldor John , Vallely Andrew , Canfell Karen
Published: March 2022

Introduction

WHO has launched updated cervical screening guidelines, including provisions for primary HPV screen-and-treat. Papua New Guinea (PNG) has a high burden of cervical cancer, but no national cervical screening programme. We recently completed the first field trials of a screen-and-treat algorithm using point-of-care self-collected HPV and same-day treatment (hereafter self-collected HPV S&T) and showed this had superior clinical performance and acceptability to visual inspection of the cervix with acetic acid (VIA). We, therefore, evaluated the effectiveness, cost-effectiveness and resource implications of a national cervical screening programme using self-collected HPV S&T compared with VIA in PNG.

Methods

An extensively validated platform (‘Policy1-Cervix’) was calibrated to PNG. A total of 38 strategies were selected for investigation, and these incorporated variations in age ranges and screening frequencies and allowed for the identification of the optimal strategy across a wide range of possibilities. A selection of strategies that were identified as being the most effective and cost-effective were then selected for further investigation for longer-term outcomes and budget impact estimation. In the base case, we assumed primary HPV testing has a sensitivity to cervical intraepithelial neoplasia 2 (CIN2+) + of 91.8% and primary VIA of 51.5% based on our earlier field evaluation combined with evidence from the literature. We conservatively assumed HPV sampling and testing would cost US$18. Costs were estimated from a service provider perspective based on data from local field trials and local consultation.

Results

Self-collected HPV S&T was more effective and more cost-effective than VIA. Either twice or thrice lifetime self-collected HPV S&T would be cost-effective at 0.5× gross domestic product (GDP) per capita (incremental cost-effectiveness ratio: US$460–US$656/life-years saved; 1GDPper-capita: US$2829 or PGK9446 (year 2019)) and could prevent 33 000–42 000 cases and 23 000–29 000 deaths in PNG over the next 50 years, if scale-up reached 70% coverage from 2023.

Conclusion

Self-collected HPV S&T was effective and cost-effective in the high-burden, low-resource setting of PNG, and, if scaled-up rapidly, could prevent over 20 000 deaths over the next 50 years. VIA screening was not effective or cost-effective. These findings support, at a country level, WHO updated cervical screening guidelines and indicate that similar approaches could be appropriate for other low-resource settings.
Utility of KI-67 as a prognostic biomarker in pulmonary neuroendocrine neoplasms: a systematic review and meta-analysis
Authors: Naheed Salma , Holden Chloe , Tanno Lulu , Pattini Linda , Pearce Neil W , Green Bryan , Jaynes Eleanor , Cave Judith , Ottensmeier Christian H. , Pelosi Giuseppe
Published: March 2022

Objectives

Ki-67, a marker of cellular proliferation, is associated with prognosis across a wide range of tumours, including gastroenteropancreatic neuroendocrine neoplasms (NENs), lymphoma, urothelial tumours and breast carcinomas. Its omission from the classification system of pulmonary NENs is controversial. This systematic review sought to assess whether Ki-67 is a prognostic biomarker in lung NENs and, if feasible, proceed to a meta-analysis.

Research design and methods

Medline (Ovid), Embase, Scopus and the Cochrane library were searched for studies published prior to 28 February 2019 and investigating the role of Ki-67 in lung NENs. Eligible studies were those that included more than 20 patients and provided details of survival outcomes, namely, HRs with CIs according to Ki-67 percentage. Studies not available as a full text or without an English manuscript were excluded. This study was prospectively registered with PROSPERO.

Results

Of 11 814 records identified, seven studies met the inclusion criteria. These retrospective studies provided data for 1268 patients (693 TC, 281 AC, 94 large cell neuroendocrine carcinomas and 190 small cell lung carcinomas) and a meta-analysis was carried out to estimate a pooled effect. Random effects analyses demonstrated an association between a high Ki-67 index and poorer overall survival (HR of 2.02, 95% CI 1.16 to 3.52) and recurrence-free survival (HR 1.42; 95% CI 1.01 to 2.00).

Conclusion

This meta-analysis provides evidence that high Ki-67 labelling indices are associated with poor clinical outcomes for patients diagnosed with pulmonary NENs. This study is subject to inherent limitations, but it does provide valuable insights regarding the use of the biomarker Ki-67, in a rare tumour.

Prospero registration number

CRD42018093389.
Medical expenditure and its influencing factors of patients with hypertension in Shanxi Province, China: a study based on ‘System of Health Accounts 2011’ and multiple-layer perceptron neural network
Authors: Liu Guojie , Fang Quan , Ji Xinyu , OuYang Jing , Zhu Yalan , Wang Leying , Wang Xin
Published: March 2022

Objectives

To study the medical expenditure and influencing factors of patients with hypertension in Shanxi Province, China.

Design

A cross-sectional study.

Setting

1088 medical institutions, including general hospitals, traditional Chinese medicine hospitals, special hospitals, basic medical institutions and public health institutions.

Participants

180 441 hypertensive outpatients and 14 763 inpatients from 1 January to 31 December 2017.

Primary and secondary outcome measures

Curative care expenditure for hypertension (CCEht) was measured based on System of Health Accounts 2011. Influenced factors were analysed by univariate analysis and multiple layer perceptron neural network.

Results

In 2017, CCEhtwas US$307.71 million, accounting for 3.63% of total CCE and 0.14% of gross domestic product (GDP) in Shanxi Province of China. CCE of hypertensive outpatients (CCEht-out) and inpatients (CCEht-in) accounted for 44.49% and 55.51% of CCEht. Drug fee accounted for 81.55% of CCEht-outand 22.50% of CCEht-in, respectively. The top three influencing factors were drug fee, surgical fee and hospitalisation days for inpatients, and drug fee, examination fee and test fee for outpatients.

Conclusions

The medical expenditure of hypertension is still heavy for individuals and society. The diagnosis and treatment capacities of primary healthcare system has been enhanced. New rural cooperation medical insurance and urban employee basic medical insurance have a trend of overusing, and the burden of family healthcare expenditure is still heavy. To ease the economic burden of patients with hypertension and improve the efficiency of social resources utilisation, policymakers should pay more attention to key groups, further increase support for primary healthcare system, standardise the treatment and reimbursement of hypertension and incline the reimbursement policy to outpatient service.
Urban scaling of opioid overdose deaths in the USA: a cross-sectional study in three periods between 2005 and 2017
Authors: Mullachery Pricila H , Lankenau Stephen , Diez Roux Ana V , Li Ran , Henson Rosie Mae , Bilal Usama
Published: March 2022

Objectives

To describe the association between population size, population growth and opioid overdose deaths—overall and by type of opioid—in US commuting zones (CZs) in three periods between 2005 and 2017.

Settings

741 CZs covering the entirety of the US CZs are aggregations of counties based on commuting patterns that reflect local economies.

Participants

We used mortality data at the county level from 2005 to 2017 from the National Center for Health Statistics.

Outcome

Opioid overdose deaths were defined using underlying and contributory causes of death codes from the International Classification of Diseases, 10th revision (ICD-10). We used the underlying cause of death to identify all drug poisoning deaths. Contributory cause of death was used to classify opioid overdose deaths according to the three major types of opioid, that is, prescription opioids, heroin and synthetic opioids other than methadone.

Results

Opioid overdose deaths were disproportionally higher in largely populated CZs. A CZ with 1.0% larger population had 1.10%, 1.10%, and 1.16% higher opioid death count in 2005–2009, 2010–2014, and 2015–2017, respectively. This pattern was largely driven by a high number of deaths involving heroin and synthetic opioids, particularly in 2015–2017. Population growth over time was associated with lower age-adjusted opioid overdose mortality rate: a 1.0% increase in population over time was associated with 1.4% (95% CI: −2.8% to 0.1%), 4.5% (95% CI: −5.8% to −3.2%), and 1.2% (95% CI: −4.2% to 1.8%) lower opioid overdose mortality in 2005–2009, 2010–2014, and 2015–2017, respectively. The association between positive population growth and lower opioid mortality rates was stronger in larger CZs.

Conclusions

Opioid overdose mortality in the USA was disproportionately higher in mid-sized and large CZs, particularly those affected by declines in population over time, regardless of the region where they are located.
Severe acute kidney injury predicting model based on transcontinental databases: a single-centre prospective study
Authors: Liang Qiqiang , Xu Yongfeng , Zhou Yu , Chen Xinyi , Chen Juan , Huang Man
Published: March 2022

Objectives

There are many studies of acute kidney injury (AKI) diagnosis models lack of external validation and prospective validation. We constructed the models using three databases to predict severe AKI within 48 hours in intensive care unit (ICU) patients.

Design

A retrospective and prospective cohort study.

Setting

We studied critically ill patients in our database (SHZJU-ICU) and two other public databases, the Medical Information Mart for Intensive Care (MIMIC) and AmsterdamUMC databases, including basic demographics, vital signs and laboratory results. We predicted the diagnosis of severe AKI in patients in the next 48 hours using machine-learning algorithms with the three databases. Then, we carried out real-time severe AKI prediction in the prospective validation study at our centre for 1 year.

Participants

All patients included in three databases with uniform exclusion criteria.

Primary and secondary outcome measures

Effect evaluation index of prediction models.

Results

We included 58 492 patients, and a total of 5257 (9.0%) patients met the definition of severe AKI. In the internal validation of the SHZJU-ICU and MIMIC databases, the best area under the receiver operating characteristic curve (AUROC) of the model was 0.86. The external validation results by AmsterdamUMC database were also satisfactory, with the best AUROC of 0.86. A total of 2532 patients were admitted to the centre for prospective validation; 358 positive results were predicted and 344 patients were diagnosed with severe AKI, with the best sensitivity of 0.72, the specificity of 0.80 and the AUROC of 0.84.

Conclusion

The prediction model of severe AKI exhibits promises as a clinical application based on dynamic vital signs and laboratory results of multicentre databases with prospective and external validation.
Protocol for the implementation of a stepped-care model to address fear of cancer recurrence in patients previously diagnosed with early-stage (0–II) melanoma
Authors: Thompson Jake R , Smith Andrea L , Lo Serigne N , Kasparian Nadine A , Saw Robyn PM , Dieng Mbathio , Seaman Linda , Martin Linda K , Guitera Pascale , Milne Donna , Schmid Helen , Cust Anne E , Bartula Iris
Published: March 2022

Introduction

Fear of cancer recurrence (FCR) is commonly reported by patients diagnosed with early-stage (0–II) melanoma and can have a significant impact on daily functioning. This study will pilot the implementation of the Melanoma Care Program, an evidence-based, psychological intervention to reduce FCR, into routine practice, using a stepped-care model.

Methods and analysis

Intervention effectiveness and level of implementation will be investigated using a hybrid type I design. Between 4 weeks before and 1 week after their next dermatological appointment, patients with melanoma will be invited to complete the Fear of Cancer Recurrence Inventory Short-Form, measuring self-reported FCR severity. Using a stepped-care model, clinical cut-off points will guide the level of support offered to patients. This includes: (1) usual care, (2) Melanoma: Questions and Answers psychoeducational booklet, and (3) three or five psychotherapeutic telehealth sessions. This longitudinal, mixed-methods pilot implementation study aims to recruit 108 patients previously diagnosed with stage 0–II melanoma. The primary effectiveness outcome is change in FCR severity over time. Secondary effectiveness outcomes include change in anxiety, depression, stress, health-related quality of life and melanoma-related knowledge over time. All outcomes are measured at baseline, within 1 week of the final telehealth session, and 6 and 12 months post-intervention. Implementation stakeholders at each study site and interested patients will provide feedback on intervention acceptability and appropriateness. Implementation stakeholders will also provide feedback on intervention cost, feasibility, fidelity and sustainability. These outcomes will be measured throughout implementation, using questionnaires and semistructured interviews/expert group discussions. Descriptive statistics, linear mixed-effects regression and thematic analysis will be used to analyse study data.

Ethics and dissemination

Ethics approval was granted by the Sydney Local Health District–Royal Prince Alfred Zone (2020/ETH02518), protocol number: X20-0495. Results will be disseminated through peer-reviewed journals, conference presentations, social media and result summaries distributed to interested participants.

Trial registration details

(ACTRN12621000145808).
Variations of urinary N-acetyl-β-D-glucosaminidase levels and its performance in detecting acute kidney injury under different thyroid hormones levels: a prospectively recruited, observational study
Authors: Liang Silin , Luo Dandong , Hu Linhui , Fang Miaoxian , Li Jiaxin , Deng Jia , Fang Heng , Zhang Huidan , He Linling , Xu Jing , Liang Yufan , Chen Chunbo
Published: March 2022

Objective

Changes in thyroid function will be accompanied by changes in urinary N-acetyl-β-D-glucosaminidase (uNAG) levels. Therefore, whether thyroid hormones interfere the ability of uNAG in detecting acute kidney injury (AKI) has raised concern in patients with critical illness.

Design

A prospectively recruited, observational study was performed.

Setting

Adults admitted to the intensive care unit of a grade A tertiary hospital in China.

Participants

A total of 1919 critically ill patients were enrolled in the study.

Main outcome measures

To investigate the variations of the ability of uNAG to detect AKI in patients with critical illness under different thyroid hormones levels (differences in area under the curve (AUC) for uNAG diagnosis and prediction of AKI with different thyroid hormones levels).

Results

The bivariate correlation analysis revealed that FT3 and TT3 levels were independently associated with uNAG levels (p<0.001). FT3 and uNAG also showed correlation in multivariable linear regression analysis (p<0.001). After stratification according to the levels of FT3 or TT3, significant variation was observed in the uNAG levels with different quartiles (p<0.05). However, in patients with varying FT3 and TT3 levels, no significant difference was found in the AUCs of uNAG to detect AKI (p>0.05).

Conclusions

Even if uNAG levels varied with FT3 and TT3 levels, these hormones did not interfere with uNAG’s ability to detect AKI in patients with critical illness.
Randomised, open-label, multicentric phase III trial to evaluate the safety and efficacy of palbociclib in combination with endocrine therapy, guided by ESR1 mutation monitoring in oestrogen receptor-positive, HER2-negative metastatic breast cancer patients: study design of PADA-1
Authors: Berger Frédérique , Marce Margaux , Delaloge Suzette , Hardy-Bessard Anne-Claire , Bachelot Thomas , Bièche Ivan , Pradines Anne , De La Motte Rouge Thibault , Canon Jean-Luc , André Fabrice , Arnould Laurent , Clatot Florian , Lemonnier Jérôme , Marques Sandrine , Bidard François-Clement
Published: March 2022

Introduction

The combination of a CDK4/6 inhibitor with an aromatase inhibitor (AI) has recently become the gold standard for AI-sensitive first line treatment of oestrogen receptor-positive (ER+) HER2-negative (HER2−) advanced breast cancer. However, most patients receiving this combination will ultimately progress and require further therapies.

Several studies have demonstrated that the onset of a ESR1 gene mutation lead to AIs resistance in the advanced setting. ESR1 mutations can be detected in circulating tumour DNA (ctDNA) using a digital PCR assay. Our study aims to prove the clinical efficacy of periodic monitoring for emerging or rise of ESR1 mutations in ctDNA to trigger an early change from AI plus palbociclib to fulvestrant plus palbociclib treatment while assessing global safety.

Methods

PADA-1 is a randomised, open-label, multicentric, phase III trial conducted in patients receiving AI and palbociclib as first line therapy for metastatic ER +HER2- breast cancer. 1000 patients will be included and treated with palbociclib in combination with an AI. Patients will be screened for circulating blood ESR1 mutation detection at regular intervals. Patients for whom a rising circulating ESR1 mutation is detected without tumour progression (up to N=200) will be randomised (1:1) between (1) Arm A: no modification of therapy; and (2) Arm B: palbociclib in combination with fulvestrant, a selective ER down-regulator. At tumour progression, an optional crossover will be offered to patients randomised in arm A. The coprimary endpoints are (1) Grade ≥3 haematological toxicities and their associations with baseline characteristics and (2) progression-free survival in randomised patients.

Ethics and dissemination

The study has been approved by the French medicines agency (ANSM) and by an ethics committee (ref 01/17_1 CPP Ouest-IV Nantes) in January 2017. The trial results will be published in academic conference presentations and international peer-reviewed journals.

Trial registration numbers

EudraCT: 2016-004360-18; NCT03079011.
Early impact of the COVID-19 pandemic on in-person outpatient care utilisation: a rapid review
Authors: Dupraz Julien , Le Pogam Marie-Annick , Peytremann-Bridevaux Isabelle
Published: March 2022

Objectives

To quantitatively assess the early impact of the COVID-19 pandemic on in-person outpatient care utilisation worldwide, as well as across categories of services, types of care and medical specialties.

Design

Rapid review.

Method

A search of MEDLINE and Embase was conducted to identify studies published from 1 January 2020 to 12 February 2021, which quantitatively reported the impact of the COVID-19 pandemic on the amount of outpatient care services delivered (in-person visits, diagnostic/screening procedures and treatments). There was no restriction on the type of medical care (emergency/primary/specialty care) or target population (adult/paediatric). All articles presenting primary data from studies reporting on outpatient care utilisation were included. Studies describing conditions requiring hospitalisation or limited to telehealth services were excluded.

Results

A total of 517 articles reporting 1011 outpatient care utilisation measures in 49 countries worldwide were eligible for inclusion. Of those, 93% focused on the first semester of 2020 (January to June). The reported results showed an almost universal decline in in-person outpatient care utilisation, with a 56% overall median relative decrease. Heterogeneity across countries was high, with median decreases ranging from 10% to 91%. Diagnostic and screening procedures (−63%), as well as in-person visits (−56%), were more affected than treatments (−36%). Emergency care showed a smaller relative decline (−49%) than primary (−60%) and specialty care (−58%).

Conclusions

The provision of in-person outpatient care services has been strongly impacted by the COVID-19 pandemic, but heterogeneously across countries. The long-term population health consequences of the disruption of outpatient care service delivery remain currently unknown and need to be studied.

PROSPERO registration number

CRD42021237366.
Ventilation management and outcomes in out-of-hospital cardiac arrest: a protocol for a preplanned secondary analysis of the TTM2 trial
Authors: Robba Chiara , Nielsen Niklas , Dankiewicz Josef , Badenes Rafael , Battaglini Denise , Ball Lorenzo , Brunetti Iole , Pedro David Wendel-Garcia , Young Paul , Eastwood Glenn , Chew Michelle S , Jakobsen Janus , Unden Johan , Thomas Matthew , Joannidis Michael , Nichol Alistair , Lundin Andreas , Hollenberg Jacob , Lilja Gisela , Hammond Naomi E , Saxena Manoj , Martin Annborn , Solar Miroslav , Taccone Fabio Silvio , Friberg Hans A , Pelosi Paolo
Published: March 2022

Introduction

Mechanical ventilation is a fundamental component in the management of patients post cardiac arrest. However, the ventilator settings and the gas-exchange targets used after cardiac arrest may not be optimal to minimise post-anoxic secondary brain injury. Therefore, questions remain regarding the best ventilator management in such patients.

Methods and analysis

This is a preplanned analysis of the international randomised controlled trial, targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (OHCA)–target temperature management 2 (TTM2). The primary objective is to describe ventilatory settings and gas exchange in patients who required invasive mechanical ventilation and included in the TTM2 trial. Secondary objectives include evaluating the association of ventilator settings and gas-exchange values with 6 months mortality and neurological outcome. Adult patients after an OHCA who were included in the TTM2 trial and who received invasive mechanical ventilation will be eligible for this analysis. Data collected in the TTM2 trial that will be analysed include patients’ prehospital characteristics, clinical examination, ventilator settings and arterial blood gases recorded at hospital and intensive care unit (ICU) admission and daily during ICU stay.

Ethics and dissemination

The TTM2 study has been approved by the regional ethics committee at Lund University and by all relevant ethics boards in participating countries. No further ethical committee approval is required for this secondary analysis. Data will be disseminated to the scientific community by abstracts and by original articles submitted to peer-reviewed journals.

Trial registration number

NCT02908308.
Efficacy and predictive biomarkers of immunotherapy in Epstein-Barr virus-associated gastric cancer
Authors: Bai Yuezong , Xie Tong , Wang Zhenghang , Tong Shuang , Zhao Xiaochen , Zhao Feilong , Cai Jinping , Wei Xiaofan , Peng Zhi , Shen Lin
Published: March 2022

Background

Epstein-Barr virus (EBV)-associated gastric cancer (GC) (EBVaGC) is a distinct molecular subtype of GC with a favorable prognosis. However, the exact effects and potential mechanisms of EBV infection on immune checkpoint blockade (ICB) efficacy in GC remain to be clarified. Additionally, EBV-encoded RNA (EBER) in situ hybridization (ISH), the traditional method to detect EBV, could cause false-positive/false-negative results and not allow for characterizing other molecular biomarkers recommended by standard treatment guidelines for GC. Herein, we sought to investigate the efficacy and potential biomarkers of ICB in EBVaGC identified by next-generation sequencing (NGS).

Design

An NGS-based algorithm for detecting EBV was established and validated using two independent GC cohorts (124 in the training cohort and 76 in the validation cohort). The value of EBV infection for predicting ICB efficacy was evaluated among 95 patients with advanced or metastatic GC receiving ICB. The molecular predictive biomarkers for ICB efficacy were identified to improve the prediction accuracy of ICB efficacy in 22 patients with EBVaGC.

Results

Compared with orthogonal assay (EBER-ISH) results, the NGS-based algorithm achieved high performance with a sensitivity of 95.7% (22/23) and a specificity of 100% (53/53). EBV status was identified as an independent predictive factor for overall survival and progression-free survival in patients with DNA mismatch repair proficient (pMMR) GC following ICB. Moreover, the patients with EBV+/pMMR and EBV−/MMR deficient (dMMR) had comparable and favorable survival following ICB. Twenty-two patients with EBV+/pMMR achieved an objective response rate of 54.5% (12/22) on immunotherapy. Patients with EBVaGC with a high cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) level were less responsive to anti-programmed death-1/ligand 1 (PD-1/L1) monotherapy, and the combination of anti-CTLA-4 plus anti-PD-1/L1 checkpoint blockade benefited patients with EBVaGC more than anti-PD-1/L1 monotherapy with a trend close to significance (p=0.074). There were nearly significant differences in tumor mutational burden (TMB) level andSMARCA4mutation frequency between the ICB response and non-response group.

Conclusions

We developed an efficient NGS-based EBV detection strategy, and this strategy-identified EBV infection was as effective as dMMR in predicting ICB efficacy in GC. Additionally, we identified CTLA-4, TMB, andSMARCA4mutation as potential predictive biomarkers of ICB efficacy in EBVaGC, which might better inform ICB treatment for EBVaGC.
Spontaneous tumor regression following COVID-19 vaccination
Authors: Sousa Luana Guimaraes de , McGrail Daniel J , Li Kaiyi , Marques-Piubelli Mario L , Gonzalez Cipriano , Dai Hui , Ferri-Borgogno Sammy , Godoy Myrna , Burks Jared , Lin Shiaw-Yih , Bell Diana , Ferrarotto Renata
Published: March 2022

Vaccination against COVID-19 is critical for immuno-compromised individuals, including patients with cancer. Systemic reactogenicity, a manifestation of the innate immune response to vaccines, occurs in up to 69% of patients following vaccination with RNA-based COVID-19 vaccines. Tumor regression can occur following an intense immune-inflammatory response and novel strategies to treat cancer rely on manipulating the host immune system. Here, we report spontaneous regression of metastatic salivary gland myoepithelial carcinoma in a patient who experienced grade 3 systemic reactogenicity, following vaccination with the mRNA-1273 COVID-19 vaccine. Histological and immunophenotypic inspection of the postvaccination lung biopsy specimens showed a massive inflammatory infiltrate with scant embedded tumor clusters (<5%). Highly multiplexed imaging mass cytometry showed that the postvaccination lung metastasis samples had remarkable immune cell infiltration, including CD4+ T cells, CD8+ T cells, natural killer cells, B cells, and dendritic cells, which contrasted with very low levels of these cells in the prevaccination primary tumor and lung metastasis samples. CT scans obtained 3, 6, and 9 months after the second vaccine dose demonstrated persistent tumor shrinkage (50%, 67%, and 73% reduction, respectively), suggesting that vaccination stimulated anticancer immunity.Insight:This case suggests that the mRNA-1273 COVID-19 vaccine stimulated anticancer immunity and tumor regression.
Geriatric trauma prognosis trends over 10 years: analysis of a nationwide trauma registry
Authors: Nishimura Takeshi , Naito Hiromichi , Nakao Atsunori , Nakayama Shinichi
Published: March 2022

Purpose

With Japan’s population rapidly skewing toward aging, the number of geriatric trauma patients is expected to increase. Since we need to continue to improve the quality of geriatric trauma patient care, this study aimed to evaluate in-hospital mortality trends among geriatric trauma patients in Japan over a recent 10-year period.

Methods

This was a retrospective cohort study of data from a Japanese nationwide trauma registry (the Japan National Trauma Data Bank) on patients admitted between January 1, 2008 and December 31, 2017. Geriatric patients were defined as those 65 years old and older. The primary outcome was to clarify in-hospital mortality trends and changes over these 10 years.

Results

We identified 265 268 eligible trauma patients. Excluding those under 65 years old and those with inadequate or unknown age data, missing prognosis, out-of-hospital cardiac arrest, and burns, 107 766 patients were enrolled in this study. The total trauma patient in-hospital mortality trend was evaluated using the Cochran-Armitage test and showed a significant decrease (p<0.001). Although severe trauma patients (Injury Severity Score (ISS) ≥16) showed a significant decreasing trend (p<0.001) over time (from 26.1% to 14.5%), less-severe trauma patients (ISS <16) did not (p=0.41) (from 2.7% to 2.1%). Mixed logistic regression analysis showed that the number of year patients stayed in the hospital was significantly associated with mortality.

Conclusions

While recognizing the limitations of the current analysis, our data demonstrated that prognoses for severe trauma patients over 65 years old improved dramatically over these 10 years, especially in those with severe trauma.

Level of evidence

Ⅲ—retrospective cohort study.
Predicting fatigue service life reductions of asphalt pavements due to deficiency in design-level values of effective binder content
Authors: Mirzahosseini Mohammadreza , Lee Jusang , Olek Jan , Jeon Jongmyung , Nantung Tommy E.
Published: March 2022

The focus of this study is the evaluation of the effects of deficiencies in design-level values of effective binder content (Δ Vbe) on the top-down (TD) and bottom-up (BU) fatigue cracking performance of hot-mix asphalt (HMA) mixtures using AASHTOWare Pavement ME Design structural simulation program. Using an analytical–mathematical-based methodology, this study also aims to predict the reduction in fatigue service life (i.e., TD, and BU fatigue cracking) of asphalt pavements that are most sensitive to the variation (Δ Vbe). Two types of mixes with varying levels of Vbe are used to simulate the fatigue cracking performance of a full-depth (FD) pavement structure. For each of the three studied cases, one asphalt course has a variable value of Vbe, while the two other courses have a fixed value of Vbe. Results indicate that the Δ Vbe of 3% reduced 50%–70% of fatigue cracking service life. Additionally, Pavement ME shows a limitation to account for the effect of Vbe in the intermediate course on the BU fatigue cracking.
Analysis and classification of privacy-sensitive content in social media posts
Authors: Bioglio Livio , Pensa Ruggero G.
Published: March 2022

User-generated contents often contain private information, even when they are shared publicly on social media and on the web in general. Although many filtering and natural language approaches for automatically detecting obscenities or hate speech have been proposed, determining whether a shared post contains sensitive information is still an open issue. The problem has been addressed by assuming, for instance, that sensitive contents are published anonymously, on anonymous social media platforms or with more restrictive privacy settings, but these assumptions are far from being realistic, since the authors of posts often underestimate or overlook their actual exposure to privacy risks. Hence, in this paper, we address the problem of content sensitivity analysis directly, by presenting and characterizing a new annotated corpus with around ten thousand posts, each one annotated as sensitive or non-sensitive by a pool of experts. We characterize our data with respect to the closely-related problem of self-disclosure, pointing out the main differences between the two tasks. We also present the results of several deep neural network models that outperform previous naive attempts of classifying social media posts according to their sensitivity, and show that state-of-the-art approaches based on anonymity and lexical analysis do not work in realistic application scenarios.
A gauge-theoretic approach of noncommutative gravity in four dimensions
Authors: Manolakos G. , Manousselis P. , Zoupanos G.
Published: March 2022

We recall the well-known description of the conformal gravity as a gauge theory and translate the program to the noncommutative framework by constructing a gravity model on a covariant 4D noncommutative space. After determining the action of the theory we proceed to a symmetry breaking scheme by the imposition of constraints.
COMPARATIVE EVALUATION OF EFFICACY OF PERCUTANEOUS INTRADISCAL RADIOFREQUENCY ABLATION AND PLATELET RICH PLASMA INJECTION FOR DISCOGENIC LOW BACK PAIN: A PROSPECTIVE RANDOMIZED TRIAL
Authors: Goyal Titiksha , Paswan Anil Kumar , Jain Dhruv , Verma Nimisha , Dubey Rajeev Kumar
Published: March 2022

Background: Discogenic pain is a common, yet underdiagnosed cause of low backache, for which a wide array of radiofrequency (RF) ablative techniques and regenerative therapies have been tried with variable results. The objective of the study was to compare pain relief and improvement in function between percutaneous intradiscal RF ablation and platelet-rich plasma (PRP) injection for the treatment of discogenic low backache.

Methods: This double-blind, randomized, parallel-group interventional study was carried out in patients with chronic lumbar discogenic pain. Twenty-four patients each in percutaneous intradiscal radiofrequency (PIRF) ablation (Group R) and PRP injection (Group P) groups were analyzed. Numeric Rating Scale (NRS) and Oswestry Disability Index (ODI) were calculated before the procedure, and at 3 and 6 months after the procedure.

Results: At 3 months, NRS score was significantly less in group R compared to group P ([Formula: see text]). However at 6 months, there was no statistically significant difference between NRS and ODI of both groups ([Formula: see text] and 0.369, respectively). Both NRS and ODI decreased significantly over 6 months within each group.

Conclusion: No significant difference in efficacy of PIRF ablation and intradiscal PRP injection was observed at 6 months follow-up, although there was a significant improvement in pain and disability with both the procedures.
On the singular Weinstein conjecture and the existence of escape orbits for b-Beltrami fields
Authors: Miranda Eva , Oms Cédric , Peralta-Salas Daniel
Published: March 2022

Motivated by Poincaré’s orbits going to infinity in the (restricted) three-body problem [see H. Poincaré, Les Méthodes Nouvelles de la Mécanique Céleste, Vol. 3 (Gauthier-Villars, 1899) and A. Chenciner, Poincaré and the three-body problem, in Henri Poincaré, 1912–2012 (Birkhäuser, Basel, 2015), pp. 51–149], we investigate the generic existence of heteroclinic-like orbits in a neighborhood of the critical set of a [Formula: see text]-contact form. This is done by using a singular counterpart [R. Cardona, E. Miranda and D. Peralta-Salas, Euler flows and singular geometric structures, Philos. Trans. R. Soc. A 377(2158) (2019) 20190034] of Etnyre–Ghrist’s contact/Beltrami correspondence [J. Etnyre and R. Ghrist, Contact topology and hydrodynamics: I. Beltrami fields and the Seifert conjecture, Nonlinearity 13(2) (2000) 441–458], and genericity results concerning eigenfunctions of the Laplacian established by Uhlenbeck [Generic properties of eigenfunctions, Amer. J. Math. 98(4) (1976) 1059–1078]. Specifically, we analyze the [Formula: see text]-Beltrami vector fields on [Formula: see text]-manifolds of dimension [Formula: see text] and prove that for a generic asymptotically exact [Formula: see text]-metric they exhibit escape orbits. We also show that a generic asymptotically symmetric [Formula: see text]-Beltrami vector field on an asymptotically flat [Formula: see text]-manifold has a generalized singular periodic orbit and at least four escape orbits. Generalized singular periodic orbits are trajectories of the vector field whose [Formula: see text]- and [Formula: see text]-limit sets intersect the critical surface. These results are a first step towards proving the singular Weinstein conjecture.
On rings with finite Gorenstein weak global dimension
Authors: Wang Junpeng , Zhang Xiaoxiang
Published: March 2022

Let [Formula: see text] be a ring with finite Gorenstein weak global dimension. We characterize Gorenstein projective, injective and flat modules over [Formula: see text]. As an application, it is proved that [Formula: see text] is (strongly) CM-free if and only if [Formula: see text] has finite weak global dimension.
Experimental Validation of a Novel Concept to Reduce Optical Surface Wave Front Errors by Using Deformable Bushes at Opto-Mechanical Interfaces
Authors: Nagabhushana S. , Prasad B. Raghavendra , Nagesh Suresh , Nara Suresh Venkata , Sandeep D. S. , Kamath P. U. , Misra Shalab , Hegde Bhavana , Utkarsha D. , Sinha Mrityunjay Kumar , Kathiravan S. , Natarajan V. , Kumar S. Pawan , Kumar Amit
Published: March 2022

One of the major objectives of the optomechanics is to support large optics required for the purpose and also to maintain high dynamic stability in operation. This requirement calls for more number of supports, to support large optics. While addressing this issue, the mounting system tends to become non-kinematic and distorts the optical surface and leads to poor image quality. The distorted optical surfaces bring in increased RMS surface wavefront errors which will result in poor image quality. In this context, a new concept is proposed in our previous publication ( Nagabhushana et al., 2021 ) which involves introduction of deformable bushes at the optomechanical interfaces. These are deformed by applied clamping forces and also enabling all degrees of freedom (DOF) to be arrested. This also ensures that the clamping force in axial DOF is limited to a minimal value. This technique enables to arrest of axial DOF without exerting the clamping force on the optomechanical assembly there by reduces optical aberrations and improves the mounting system’s dynamic stability. This is because deformable bushes absorb all the clamping forces and the strain has no impact on the mount and therefore does not lead deformation of the optical surface. The clamping forces are simulated by Finite Element (FE) methods. Further, in this paper, the concept is verified and validated by experiments. The simulation results are observed to be in close correlation with experiment results. Improved stability is also observed by additional constraints introduced to optomechanical mounts with no compromise in wavefront errors.
Deep Reinforcement Learning-based Trajectory Pricing on Ride-hailing Platforms
Authors: Huang Jianbin , Huang Longji , Liu Meijuan , Li He , Tan Qinglin , Ma Xiaoke , Cui Jiangtao , Huang De-Shuang
Published: March 2022

Dynamic pricing plays an important role in solving the problems such as traffic load reduction, congestion control, and revenue improvement. Efficient dynamic pricing strategies can increase capacity utilization, total revenue of service providers, and the satisfaction of both passengers and drivers. Many proposed dynamic pricing technologies focus on short-term optimization and face poor scalability in modeling long-term goals for the limitations of solution optimality and prohibitive computation. In this article, a deep reinforcement learning framework is proposed to tackle the dynamic pricing problem for ride-hailing platforms. A soft actor-critic (SAC) algorithm is adopted in the reinforcement learning framework. First, the dynamic pricing problem is translated into a
Markov Decision Process (MDP)
and is set up in continuous action spaces, which is no need for the discretization of action space. Then, a new reward function is obtained by the order response rate and the KL-divergence between supply distribution and demand distribution. Experiments and case studies demonstrate that the proposed method outperforms the baselines in terms of order response rate and total revenue.
Algorithms for Trajectory Points Clustering in Location-based Social Networks
Authors: Han Nan , Qiao Shaojie , Yue Kun , Huang Jianbin , He Qiang , Tang Tingting , Huang Faliang , He Chunlin , Yuan Chang-An
Published: March 2022

Recent advances in localization techniques have fundamentally enhanced social networking services, allowing users to share their locations and location-related contents. This has further increased the popularity of location-based social networks (LBSNs) and produces a huge amount of trajectories composed of continuous and complex spatio-temporal points from people’s daily lives. How to accurately aggregate large-scale trajectories is an important and challenging task. Conventional clustering algorithms (e.g.,
k
-means or
k
-mediods) cannot be directly employed to process trajectory data due to their serialization, triviality and redundancy. Aiming to overcome the drawbacks of traditional
k
-means algorithm and
k
-mediods, including their sensitivity to the selection of the initial
k
value, the cluster centers and easy convergence to a locally optimal solution, we first propose an optimized
k
-means algorithm (namely
OKM
) to obtain
k
optimal initial clustering centers based on the density of trajectory points. Second, because
k
-means is sensitive to noisy points, we propose an improved
k
-mediods algorithm called
IKMD
based on an acceptable radius
r
by considering users’ geographic location in LBSNs. The value of
k
can be calculated based on
r
, and the optimal
k
points are selected as the initial clustering centers with high densities to reduce the cost of distance calculation. Thirdly, we thoroughly analyze the advantages of
IKMD
by comparing it with the commonly used clustering approaches through illustrative examples. Last, we conduct extensive experiments to evaluate the performance of
IKMD
against seven clustering approaches including the proposed optimized
k
-means algorithm,
k
-mediods algorithm, traditional density-based
k
-mediods algorithm and the state-of-the-arts trajectory clustering methods. The results demonstrate that
IKMD
significantly outperforms existing algorithms in the cost of distance calculation and the convergence speed. The methods proposed is proved to contribute to a larger effort targeted at advancing the study of intelligent trajectory data analytics.