bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical activity of PD-1 inhibition in the treatment of locally advanced or metastatic basal cell carcinoma
Authors: In Gino Kim , Nallagangula Aparna , Choi Jacob Seung , Tachiki Lisa , Blackburn Matthew J , Capone Stephen , Bollin Kathryn B , Reuben Daniel Y. , Shirai Keisuke , Zhang-Nunes Sandy , Ragab Omar , Terando Alicia , Hu Jenny C. , Lee Han , Bhatia Shailender , Chandra Sunandana , Lutzky Jose , Gibney Geoffrey Thomas 
Published: May 2022

BackgroundBasal cell carcinoma (BCC) is the most common malignancy worldwide, yet the management of patients with advanced or metastatic disease is challenging, with limited treatment options. Recently, programmed death receptor 1 (PD-1) inhibition has demonstrated activity in BCC after prior Hedgehog inhibitor treatment.MethodsWe conducted a multicenter, retrospective analysis of BCC patients treated with PD-1 inhibitor therapy. We examined the efficacy and safety of PD-1 therapy, as well as clinical and pathological variables in association with outcomes. Progression-free survival (PFS), overall survival (OS) and duration of response (DOR) were calculated using Kaplan-Meier methodology. Toxicity was graded per Common Terminology Criteria for Adverse Events V.5.0.ResultsA total of 29 patients with BCC who were treated with PD-1 inhibition were included for analysis, including 20 (69.0%) with locally advanced and 9 (31.0%) with metastatic disease. The objective response rate was 31.0%, with five partial responses (17.2%), and four complete responses (13.8%). Nine patients had stable disease (31.0%), with a disease control rate of 62.1%. The median DOR was not reached. Median PFS was 12.2 months (95% CI 0.0 to 27.4). Median OS was 32.4 months (95% CI 18.1 to 46.7). Two patients (6.9%) developed grade 3 or higher toxicity, while four patients (13.8%) discontinued PD-1 inhibition because of toxicity. Higher platelets (p=0.022) and any grade toxicity (p=0.024) were significantly associated with disease control rate.ConclusionsThe clinical efficacy of PD-1 inhibition among patients with advanced or metastatic BCC in this real-world cohort were comparable to published trial data. Further investigation of PD-1 inhibition is needed to define its optimal role for patients with this disease.
Genetic architecture in neonatal intensive care unit patients with congenital heart defects: a retrospective study from the China Neonatal Genomes Project
Authors: Wang Huijun , Xiao Feifan , Qian Yanyan , Wu Bingbing , Dong Xinran , Lu Yulan , Cheng Guoqiang , Wang Laishuan , Yan Kai , Yang Lin , Chen Liping , Kang Wenqing , Li Long , Pan Xinnian , Wei Qiufen , Zhuang Deyi , Chen Dongmei , Yin Zhaoqing , Yang Ling , Ni Qi , Liu Renchao , Li Gang , Zhang Ping , Li Xu , Peng Xiaomin , Wang Yao , Chen Huiyao , Ma Xiaojing , Liu Fang , Cao Yun , Huang Guoying , Zhou Wenhao 
Published: May 2022

BackgroundCongenital heart defects (CHDs) are the most common type of birth defects. The genetic aetiology of CHD is complex and incompletely understood. The overall distribution of genetic causes in patients with CHD from neonatal intensive care units (NICUs) needs to be studied.MethodsCHD cases were extracted from the China Neonatal Genomes Project (2016–2021). Next-generation sequencing results and medical records were retrospectively evaluated to note the frequency of genetic diagnosis and the respective patient outcomes.ResultsIn total, 1795 patients were included. The human phenotype ontology term of atrial septal defect, patent ductus arteriosus and ventricular septal defect account for a large portion of the CHD subtype. Co-occurring extracardiac anomalies were observed in 35.1% of patients. 269 of the cases received genetic diagnoses that could explain the phenotype of CHDs, including 172 copy number variations and 97 pathogenic variants. The detection rate of trio-whole-exome sequencing was higher than clinical exome sequencing (21.8% vs 14.5%, p<0.05). Further follow-up analysis showed the genetic diagnostic rate was higher in the deceased group than in the surviving group (29.0% vs 11.9%, p<0.05).ConclusionThis is the largest cohort study to explore the genetic spectrum of patients with CHD in the NICU in China. Our findings may benefit future work on improving genetic screening and counselling for NICU patients with CHD.
Combining biomarkers for prognostic modelling of Parkinson’s disease
Authors: Vijiaratnam Nirosen , Lawton Michael , Heslegrave Amanda J , Guo Tong , Tan Manuela , Jabbari Edwin , Real Raquel , Woodside John , Grosset Katherine , Chelban Viorica , Athauda Dilan , Girges Christine , Barker Roger A , Hardy John , Wood Nicholas , Houlden Henry , Williams Nigel , Ben-Shlomo Yoav , Zetterberg Henrik , Grosset Donald G , Foltynie Thomas , Morris Huw R 
Published: May 2022

BackgroundPatients with Parkinson’s disease (PD) have variable rates of progression. More accurate prediction of progression could improve selection for clinical trials. Although some variance in clinical progression can be predicted by age at onset and phenotype, we hypothesise that this can be further improved by blood biomarkers.ObjectiveTo determine if blood biomarkers (serum neurofilament light (NfL) and genetic status (glucocerebrosidase,GBAand apolipoprotein E (APOE))) are useful in addition to clinical measures for prognostic modelling in PD.MethodsWe evaluated the relationship between serum NfL and baseline and longitudinal clinical measures as well as patients’ genetic (GBAandAPOE) status. We classified patients as having a favourable or an unfavourable outcome based on a previously validated model, and explored how blood biomarkers compared with clinical variables in distinguishing prognostic phenotypes .Results291 patients were assessed in this study. Baseline serum NfL was associated with baseline cognitive status. Nfl predicted a shorter time to dementia, postural instability and death (dementia—HR 2.64; postural instability—HR 1.32; mortality—HR 1.89) whereas APOEe4 status was associated with progression to dementia (dementia—HR 3.12, 95% CI 1.63 to 6.00). NfL levels and genetic variables predicted unfavourable progression to a similar extent as clinical predictors. The combination of clinical, NfL and genetic data produced a stronger prediction of unfavourable outcomes compared with age and gender (area under the curve: 0.74-age/gender vs 0.84-ALL p=0.0103).ConclusionsClinical trials of disease-modifying therapies might usefully stratify patients using clinical, genetic and NfL status at the time of recruitment.
Delirium and the risk of developing dementia: a cohort study of 12 949 patients
Authors: Leighton Samuel P , Herron James W , Jackson Eric , Sheridan Matthew , Deligianni Fani , Cavanagh Jonathan 
Published: May 2022

BackgroundDelirium is an important risk factor for subsequent dementia. However, the field lacks large studies with long-term follow-up of delirium in subjects initially free of dementia to clearly establish clinical trajectories.MethodsWe undertook a retrospective cohort study of all patients over the age of 65 diagnosed with an episode of delirium who were initially dementia free at onset of delirium within National Health Service Greater Glasgow & Clyde between 1996 and 2020 using the Safe Haven database. We estimated the cumulative incidence of dementia accounting for the competing risk of death without a dementia diagnosis. We modelled the effects of age at delirium diagnosis, sex and socioeconomic deprivation on the cause-specific hazard of dementia via cox regression.Results12 949 patients with an incident episode of delirium were included and followed up for an average of 741 days. The estimated cumulative incidence of dementia was 31% by 5 years. The estimated cumulative incidence of the competing risk of death without dementia was 49.2% by 5 years. The cause-specific hazard of dementia was increased with higher levels of deprivation and also with advancing age from 65, plateauing and decreasing from age 90. There did not appear to be a relationship with sex.ConclusionsOur study reinforces the link between delirium and future dementia in a large cohort of patients. It highlights the importance of early recognition of delirium and prevention where possible.
Improving patient pathways for systemic lupus erythematosus: a multistakeholder pathway optimisation study
Authors: Schlencker Aurelien , Messer Laurent , Ardizzone Marc , Blaison Gilles , Hinschberger Olivier , Dahan Etienne , Sordet Christelle , Walther Julia , Dory Anne , Gonzalez Maria , Kleinlogel Stéphanie , Bramont-Nachman Aurélia , Barrand Lionel , Payen-Revol Isabelle , Sibilia Jean , Martin Thierry , Arnaud Laurent 
Published: May 2022

ObjectiveAmong the most significant challenges in SLE are the excessive diagnosis delay and the lack of coordinated care. The aim of the study was to investigate patient pathways in SLE in order to improve clinical and organisational challenges in the management of those with suspected and confirmed SLE.MethodsWe conducted a cross-sectional study of patients with SLE, healthcare providers and other representative stakeholders. Focus groups were conducted, and based on the collected data the most impactful disruption points in SLE patient pathways were identified. A novel framework to improve individual patient pathways in SLE was developed, discussed and validated during a consensus meeting with representative stakeholders.ResultsSix thematic clusters regarding disruption in optimal patient pathways in SLE were identified: appropriate and timely referral strategy for SLE diagnosis; the need for a dedicated consultation during which the diagnosis of SLE would be announced, and following which clarifications and psychological support offered; individualised patient pathways with coordinated care based on organ involvement, disease severity and patient preference; improved therapeutic patient education; prevention of complications such as infections, osteoporosis and cancer; and additional patient support. During the consensus meeting, the broader panel of stakeholders achieved consensus on these attributes and a framework for optimising SLE patient pathways was developed.ConclusionsWe have identified significant disruption points and developed a novel conceptual framework to improve individual patient pathways in SLE. These data may be of valuable interest to patients with SLE, their physicians, health organisations as well as policy makers.
Xenotransplantation and borders: two Indian narratives
Authors: Srihari Meenakshi 
Published: May 2022

This paper examines two Indian texts, Anand Gandhi’s filmThe Ship of Theseus(2012) and Manjula Padmanabhan’s playHarvest(1998), which deal with complex biopolitical and geopolitical questions around organ transplantation, for their treatment of corporeal, geopolitical and ethical borders.By dramatising the lives of carriers who are both receivers and donors, the texts enact boundaries, visible and invisible, from both sides. I focus on the carrier of the diseased organ—already a stranger, as Jean-Luc Nancy describes his own failing heart inL’Intrus(2000)—and the carrier of the alien organ and show how these raise moral and ethical questions around organ transplantation. I first argue that these texts foreground biopolitical quandaries even as they narrate the moral economies of transplantation. I then delineate the ways in which the texts employ a posthuman imaginary. The texts raise questions around organ transplantation that while emanating from the invasion of corporeal borders also reflect the permeability of social borders, and while doing so, posit the human in today’s medicalised terrain as a fragmented, multiple self that is embedded in the environment and co-evolves with it.By addressing the altered sense of self of the ‘body-in-transplant’ through a posthumanist lens that accounts for relationality and the acknowledgement of a plural self, the paper hopes to make a contribution to a better understanding of the vulnerable post-transplant patient.
Cervical spine ligamentum flavum gaps: MR characterisation and implications for interlaminar epidural injection therapy
Authors: Joshi Jatin , Roytman Michelle , Aiyer Rohit , Mauer Elizabeth , Chazen J Levi 
Published: May 2022

BackgroundCervical epidural steroid injections are commonly performed to manage pain from cervical spine disease. Cadaveric studies have demonstrated incomplete ligamentum flavum fusion in the central interlaminar region with resultant midline gaps. We performed an MR-based characterization of cervical ligamentum flavum midline gaps to improve understanding of their prevalence and guide interventionalists in procedural planning.MethodsFifty patients were retrospectively reviewed following institutional review board approval. Axial T2-weighted spinecho sequences were used to evaluate ligamentum flavum integrity at the interlaminar spaces of C5–C6, C6–C7 and C7–T1. Interlaminar spaces were further subdivided into superior, middle, and inferior portions, yielding 150 interlaminar regions characterized from C5 to T1. Subsequently, a novel categorization of gap morphology was performed, highlighting gap morphology (anterior, posterior, full, or no gap).ResultsFull gaps of the ligamentum flavum, with direct epidural space exposure, were observed with variable prevalence at all three levels evaluated. The highest incidence of full ligamentum flavum gaps were observed at C7–T1, occurring in 71.4% of patients at both its middle and inferior portions. The inferior aspect of C5–C6 demonstrated the lowest observed rates of full ligamentum flavum gap (2%).ConclusionsLigamentum flavum gaps occur in the lower cervical spine at high rates, with the highest prevalence of full thickness ligamentum flavum gaps at C7–T1. Interventionists must be aware of these important normal variants and evaluate preprocedural MRI to plan interventions.
Characterising a syndemic among black women at risk for HIV: the role of sociostructural inequity and adverse childhood experiences
Authors: Tsuyuki Kiyomi , Chan Erica , Lucea Marguerite B , Cimino Andrea , Rudolph Abby E , Tesfai Yordanos , Campbell Jacquelyn C , Catabay Christina J , Stockman Jamila K 
Published: May 2022

ObjectivesBlack women disproportionately experience STIs (including HIV/AIDS), gender-based violence, substance misuse and mental health conditions. Addressing a gap in syndemic research, we characterised comorbidity overlap within the context of sociostructural inequities and adverse childhood experiences (ACEs) among black women in Baltimore, Maryland.MethodsBetween 2015 and 2018, black women (n=305) were recruited from STI clinics in Baltimore, Maryland. Among those with complete survey data (n=230), we conducted a latent class analysis to differentiate women based on their profile of the following syndemic comorbidities: STIs, adult sexual victimisation, substance misuse and mental health disorders. We then examined the association between ACEs and syndemic latent class membership.ResultsThirty-three percent of women experienced three to nine ACEs before age 18 years, and 44% reported four to six comorbidities. The two-class latent class solution demonstrated the best fit model, and women were categorised in either class 1 (past-year STI; 59%) or class 2 (syndemic comorbidities; 41%). Women in class 2 were more likely to report unstable housing (10% vs 3%) and identify as bisexual/gay (22% vs 10%) than women in class 1. ACEs were significantly associated with an increased likelihood of class 2 membership.ConclusionsThis study reinforces the importance of screening for ACEs and offering trauma-informed, integrated care for black women with syndemic comorbidities. It also highlights the critical nature of tailoring interventions to improve sociostructural equity, preventing and reducing syndemic development.
Epidemiology and spatial distribution of people diagnosed with HIV between 1997 and 2020 in Kerman, Iran
Authors: Mirzaei Hossein , Mirzazadeh Ali , Barouni Mohsen , Ranjbar Ebrahim , Eybpoosh Sana , Sharifi Hamid 
Published: May 2022

ObjectiveThis study described the epidemiology and geographical distribution of people diagnosed with HIV in Kerman, Iran, between 1997 and 2020.MethodsWe used case-based HIV surveillance data of all people diagnosed with HIV in Kerman between 1997 and 2020. We compared the age, gender, modes of transmission and spatial distribution of newly diagnosed HIV-infected people in three time periods (1997–2004, 2005–2012 and 2013–2020). The χ2 test for trend, one-sample t-test and Kruskal-Wallis H test were used to compare the differences between the three time periods. We also used ArcGIS to map both HIV services and people living with HIV (PLWH) in 2020. The nearest neighbour index and kernel density were used to identify the spatial distribution of PLWH.ResultsA total of 459 (27.5% women) people were diagnosed with HIV during 1997–2020. The proportion of women (9.3% in 1997–2004 and 48.3% in 2013–2020, p<0.001), HIV infection through sexual contacts (11.6% in 1997–2004 and 50.3% in 2013–2020, p<0.001), HIV infection under the age of 5 years (0.8% in 1997–2004 and 5.4% in 2013–2020, p=0.01) and mean age at diagnosis among men (34.9 in 1997–2004 and 39.8 years in 2013–2020, p=0.004) significantly increased over time. 36.2% of diagnosed cases had CD4 counts under 200 x 10ˆ6/L between 2013 and 2020, with no significant improvement over time. Most newly diagnosed cases of HIV were from the eastern parts of the city. The clusters of PLWH in 2020 matched with the locations of HIV services.ConclusionWe observed important changes in HIV epidemiology regarding gender, modes of transmission, number of paediatric cases and density maps over time in Kerman. These changes should be considered for precise targeting of HIV prevention and treatment programmes.
Specific detection of Treponema pallidum in clinical samples: validation of a qPCR assay combining two genomic targets
Authors: Salle Romain , Mayslich Constance , Grange Philippe Alain , Leducq Valentin , Ollagnier Guillaume , Heller Ugo , Saule Julie , Martinet Pervenche , Robert Jean-Luc , Benhaddou Nadjet , Fouere Sebastien , Dupin Nicolas 
Published: May 2022

ObjectivesWe evaluated a real-time quantitative PCR (qPCR) for detection of the Treponema pallidum (TP) genome in clinical samples through simultaneous detection of two genomic targets.MethodsWe performed qPCR with TaqMan technology using two TP genes, polA and tpp47, as targets, with an internal positive control. The qPCR assay was compared with syphilis diagnosis based on a combination of clinical examination, serological results and inhouse nested PCR (nPCR). Samples were analysed at the National Reference Center for STIs at Cochin Hospital in Paris.ResultsIn total, from October 2010 to December 2016, 320 documented clinical samples (mucosal and cutaneous swabs) were collected from patients with or without syphilis attending STI centres in France. The qPCR had an overall sensitivity of 89% (95% CI 85.1% to 92.1%), a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 88% (95% CI 84.3% to 91.5%). The agreement between qPCR and nPCR results was 94% (κ=0.88, 95% CI 0.83 to 0.93). Calibration of the qPCR assay, by cloning both the polA and tpp47 genes, defined the detection threshold as 1 copy/µL of DNA elution.ConclusionsWe validated a new qPCR for detecting the TP genome in clinical samples with excellent sensitivity and specificity. The cloning of polA and tpp47 genes for calibration would be interesting in the evaluation of bacterial loads in samples.
Self-sampled specimens demonstrate comparable accuracy and consistency to clinician-sampled specimens for HPV detection among men who have sex with men in China
Authors: Ni Yuxin , Lu Ying , He Xi , Li Yumei , Li Yongqing , Guo Shiyu , Ong Jason J. , Xu Chen , Wang Xiaman , Yan Xumeng , Tao Yusha , Liu Na , Tang Weiming 
Published: May 2022

ObjectivesDespite a high risk of human papillomavirus (HPV) infection among men who have sex with men (MSM), few have ever tested. This study aimed to evaluate the feasibility and accuracy of HPV self-sampling among Chinese MSM, with the purpose of measuring the feasibility of self-sampling as an alternative in HPV testing scenarios.MethodsEligible participants were those who were assigned male at birth, aged 18 or above, had sex with men in the past year and had never gotten HPV vaccine. Participants followed the instructions to self-sample and were also clinician-sampled from the same anatomical sites (oral fluid, penis and rectum) in both approaches. All specimens were processed using multiplex PCR assay. The reference standard of an individual with a true positive for HPV is determined via PCR test, regardless of sampling methods. Sensitivity and specificity were calculated for each approach independently and kappa test was used to assess the consistency between the two approaches.ResultsOverall, 211 MSM were recruited at the local clinic from April to October 2020 in Zhuhai, China. The mean age was 31 years old. Only 3% of the participants sought help from healthcare providers during self-sampling. The prevalence of HPV was 49% (103 of 211). Clinician sampling detected 91 of 103 MSM infected with HPV, with a sensitivity of 88.3% (95% CI 80.2 to 93.6) and a specificity of 100.0% (95% CI 95.7 to 100.0). Self-sampling detected 81 of 103 MSM infected with HPV, with a sensitivity of 78.6% (95% CI 69.2 to 85.9) and a specificity of 100.0% (95% CI 95.7 to 100.0). The level of agreement was moderate between clinician sampling and self-sampling (k=0.67).ConclusionsSelf-sampled HPV testing demonstrated comparable accuracy and consistency to clinician sampling among MSM in China. It holds the potential to complement sexual health services especially among key populations.
Distribution of HIV self-tests by men who have sex with men attending a French sexual health centre: results of the OTO study
Authors: Gosset Daniel , Plathey Marine , Lert France , Lasry Stéphane , Jedrzejewski Thibaut , Gazalet Philippe , L'Yavanc Thomas , Pierre Nadège , Kachal Abdessamad , Frémondière Marc , Ohayon Michel , Palich Romain 
Published: May 2022

ObjectivesHIV self-tests (HSTs) have been deployed to reduce the burden of undiagnosed HIV infections in subpopulations undertested. We assumed that patients attending sexual health centres could themselves distribute HSTs in their close network. This study aimed to assess the proportion and the characteristics of the participants who distributed HSTs, as well as the characteristics of people who received HSTs.MethodsThree HSTs were given to patients attending “Le 190” Sexual Health Center, Paris, France, having consented for the study, between July 2018 and August 2020. Participants had to distribute HSTs within 6 months, preferably to individuals in their close circle who have not been tested for a long time. Then they had to complete a self-questionnaire, exploring HIV status, sexual practices, number of distributed HSTs, profile of persons who received HSTs, and if known, result of used HSTs. Univariable logistic regression was used to determine factors associated with HST distribution.ResultsOverall, 682/1062 (64%) patients accepted to be included in the study, and 283/682 (42%) completed the questionnaire. 97% were men who have sex with men (MSMs), including 86 (30%) HIV-positive individuals and 119 (42%) HIV Pre-Exposure Prophylaxis (PrEP) users. The proportion of participants having distributed 0, 1, 2 or 3 HSTs was 31%, 15%, 27% and 27%, respectively. Participants having distributed at least one HST (n=195, 69%) were more likely to have previously used HSTs themselves (OR=3.90, 95% CI=1.84 to 8.29, p<0.001). On the 901 HSTs in possession of participants who answered the questionnaire, 455 (50%) were distributed. 79% of recipients were MSMs, and 42% of whom had not been tested for more than 1 year. The result was known for 220 HSTs, including 5 positive (2.3%).ConclusionMSMs attending sexual health centres could be good disseminators of HSTs, targeting a population with high level of undiagnosed HIV infections, especially if they have already experimented it.