bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hybrid operating room with ceiling mounted imaging system assisted pre-operative and intra-operative lung nodule localization for thoracoscopic resections: a 5-year case series
Authors: Chia Audrey Qi Xin , Gogna Apoorva , Pena Angela Maria Takano , Sai Vishnu Vemula Sri , Chandramohan Sivanathan , Chan Shaun Ju Min Xavier , Ong Boon-Hean 
Published: February 2024

Abstract
Background
Video-assisted thoracoscopic (VATS) lung resections are increasingly popular and localization techniques are necessary to aid resection. We describe our experience with hybrid operating room (OR) cone-beam computed tomography (CT) assisted pre-operative and intra-operative lesion localization of lung nodules for VATS wedge resections, including our novel workflow using the hybrid OR cone-beam CT to re-evaluate patients who have undergone pre-operative localization for those who are unsuitable for intra-operative localization.

Methods
Retrospective analysis of all consecutive patients with small (≤ 20 mm), deep (≥ 10 mm distance from pleura) and/or predominantly ground-glass nodules selected for lesion localization in the Interventional Radiology suite followed by re-evaluation with cone-beam CT in the hybrid OR (pre-operative), or in the hybrid OR alone (intra-operative), prior to intentional VATS wedge performed by a single surgeon at our centre from January 2017 to December 2021.

Results
30 patients with 36 nodules underwent localization. All nodules were successfully resected with a VATS wedge resection, although 10% of localizations had hookwire or coil dislodgement. The median effective radiation dose in the pre-operative group was 10.4 mSV including a median additional radiation exposure of 0.9 mSV in the hybrid OR for reconfirmation of hookwire or coil position prior to surgery (p = 0.87). The median effective radiation dose in the intra-operative group was 3.2 mSV with a higher mean rank than the intra-operative group, suggesting a higher radiation dose (p = 0.01).

Conclusions
We demonstrate that our multidisciplinary approach utilizing the hybrid OR is safe and effective. Intra-operative localization is associated with lower radiation doses. Routine use of cone-beam CT to confirm the position of the physical marker prior to surgery in the hybrid OR helps mitigate consequences of localization failure with only a modest increase in radiation exposure.
Needs of amyloidosis patients and their care providers: design & first results of the AMY-NEEDS research and care program
Authors: Ihne-Schubert Sandra Michaela , Radovic Teresa , Fries Saskia , Frantz Stefan , Einsele Hermann , Störk Stefan , Neuderth Silke 
Published: February 2024

Abstract
Background
Amyloidosis represents a rare yet heterogeneous multi-system disorder associated with a grave prognosis and an enormous psycho-emotional strain on patients, relatives, and caregivers. We here present the overall study design and first results of AMY-NEEDS, a research program aiming to systematically assess the needs of patients suffering from amyloidosis, their relatives and health care professionals (HCPs), and develop an amyloidosis-specific care approach.

Methods
AMY-NEEDS uses a mixed-methods approach including focus groups (step 1), a questionnaire-based broad evaluation within the local amyloidosis patient collective (step 2), and the development of a needs-adapted care concept (step 3).

Results
Seven patients, six relatives and five HCPs participated in the focus groups (step 1). At the time of diagnosis, patients expressed the need of a smooth diagnostic process, possibly enhanced through improved awareness and better education of local HCPs. There was a strong wish to receive well-founded information and comprehensive support including companionship during medical visits, experience the feeling of being understood, find trust in that “everything possible” is being done, and have effortless access to centre staff. In the course of the disease, patients favoured that the specialized centre should manage treatment coordination, monitoring and psychosocial support. The interface between centre and local HCPs was regarded of particular importance, requiring further investigation into its optimal design.

Conclusions
Patients with amyloidosis express particular needs that should appropriately be considered in specifically tailored care concepts.
Performance and clinical utility of a new supervised machine-learning pipeline in detecting rare ciliopathy patients based on deep phenotyping from electronic health records and semantic similarity
Authors: Faviez Carole , Vincent Marc , Garcelon Nicolas , Boyer Olivia , Knebelmann Bertrand , Heidet Laurence , Saunier Sophie , Chen Xiaoyi , Burgun Anita 
Published: February 2024

Abstract
Background
Rare diseases affect approximately 400 million people worldwide. Many of them suffer from delayed diagnosis. Among them, NPHP1-related renal ciliopathies need to be diagnosed as early as possible as potential treatments have been recently investigated with promising results. Our objective was to develop a supervised machine learning pipeline for the detection of NPHP1 ciliopathy patients from a large number of nephrology patients using electronic health records (EHRs).

Methods and results
We designed a pipeline combining a phenotyping module re-using unstructured EHR data, a semantic similarity module to address the phenotype dependence, a feature selection step to deal with high dimensionality, an undersampling step to address the class imbalance, and a classification step with multiple train-test split for the small number of rare cases. The pipeline was applied to thirty NPHP1 patients and 7231 controls and achieved good performances (sensitivity 86% with specificity 90%). A qualitative review of the EHRs of 40 misclassified controls showed that 25% had phenotypes belonging to the ciliopathy spectrum, which demonstrates the ability of our system to detect patients with similar conditions.

Conclusions
Our pipeline reached very encouraging performance scores for pre-diagnosing ciliopathy patients. The identified patients could then undergo genetic testing. The same data-driven approach can be adapted to other rare diseases facing underdiagnosis challenges.
Identification of copy number variations among fetuses with isolated ultrasound soft markers in pregnant women not of advanced maternal age
Authors: Liu Yunyun , Liu Sha , Liu Jianlong , Bai Ting , Jing Xiaosha , Deng Cechuan , Xia Tianyu , Cheng Jing , Xing Lingling , Wei Xiang , Luo Yuan , Zhou Quanfang , Xie Dan , Xiong Yueyue , Liu Ling , Zhu Qian , Liu Hongqian 
Published: February 2024

Abstract
Background
Pathogenic (P) copy number variants (CNVs) may be associated with second-trimester ultrasound soft markers (USMs), and noninvasive prenatal screening (NIPS) can enable interrogate the entire fetal genome to screening of fetal CNVs. This study evaluated the clinical application of NIPS for detecting CNVs among fetuses with USMs in pregnant women not of advanced maternal age (AMA).

Results
Fetal aneuploidies and CNVs were identified in 6647 pregnant women using the Berry Genomics NIPS algorithm.Those with positive NIPS results underwent amniocentesis for prenatal diagnosis. The NIPS and prenatal diagnosis results were analyzed and compared among different USMs. A total of 96 pregnancies were scored positive for fetal chromosome anomalies, comprising 37 aneuploidies and 59 CNVs. Positive predictive values (PPVs) for trisomy 21, trisomy 18, trisomy 13, and sex chromosome aneuploidies were 66.67%, 80.00%, 0%, and 30.43%, respectively. NIPS sensitivity for aneuploidies was 100%. For CNVs, the PPVs were calculated as 35.59% and false positive rate of 0.57%. There were six P CNVs, two successfully identified by NIPS and four missed, of which three were below the NIPS resolution limit and one false negative. The incidence of aneuploidies was significantly higher in fetuses with absent or hypoplastic nasal bone, while that of P CNVs was significantly higher in fetuses with aberrant right subclavian artery (ARSA), compared with other groups.

Conclusions
NIPS yielded a moderate PPV for CNVs in non-AMA pregnant women with fetal USM. However, NIPS showed limited ability in identifying P CNVs. Positive NIPS results for CNVs emphasize the need for further prenatal diagnosis. We do not recommend the use of NIPS for CNVs screening in non-AMA pregnant women with fetal USM, especially in fetuses with ARSA.
Barriers to gene therapy, understanding the concerns people with haemophilia have: an exigency sub-study
Authors: Fletcher Simon , Jenner Kathryn , Holland Michael , Khair Kate 
Published: February 2024

Abstract
Background
Gene therapy has the potential to offer people with haemophilia (PwH) a life free from bleeding and the burden posed by current treatment regimens. To date, gene therapy has only been available in clinical trial settings, to PwH without pre-existing or historical factor inhibitors, significant concomitant liver damage or pre-existing neutralising antibodies to the adeno-associated viruses used to deliver the therapy. Thus, most PwH treated at centres not currently involved in gene therapy trials, either as a referral/follow-up centre or as a dosing centre, have been unable to access the therapy. This Exigency sub-study aims to gain a greater understanding of the opinions of PwH in the United Kingdom who have not had access to gene therapy: asking what they understand, what concerns they have, and whether they perceive any barriers preventing their access to gene therapy.

Results
Twenty-three PwH were approached; 14 consented, and one withdrew prior to interview. The mean age of the participants was 35.7 years (range 25–74 years). Eleven had haemophilia A and two haemophilia B. Two were treated with standard half-life factor products, five with extended half-life products, five with a FVIII mimetic and one with a clinical trial product. One family member (a participant's partner) was also interviewed. The participants identified four barriers to gene therapy: concerns about the process of gene therapy (Expectations), uncertainty about the results (outcomes), (Access) to treatment, and a lack of understanding about gene therapy (education).

Conclusions
This Exigency study subgroup sees gene therapy as a positive treatment development that promises an improved quality of life. For this participant group, four issues impact their decision to undergo gene therapy. If the promise of gene therapy is to be realised, these barriers need to be acknowledged and addressed by healthcare professionals, patient organisations, and gene therapy providers.
Clinical symptoms, biochemistry, and liver histology during the native liver period of progressive familial intrahepatic cholestasis type 2
Authors: Kondou Hiroki , Nakano Satoshi , Mizuno Tadahaya , Bessho Kazuhiko , Hasegawa Yasuhiro , Nakazawa Atsuko , Tanikawa Ken , Azuma Yoshihiro , Okamoto Tatsuya , Inui Ayano , Imagawa Kazuo , Kasahara Mureo , Zen Yoh , Suzuki Mitsuyoshi , Hayashi Hisamitsu 
Published: February 2024

Abstract
Background
Progressive familial intrahepatic cholestasis type 2 (PFIC2) is an ultra-rare disease caused by mutations in the ABCB11 gene. This study aimed to understand the course of PFIC2 during the native liver period.

Methods
From November 2014 to October 2015, a survey to identify PFIC2 patients was conducted in 207 hospitals registered with the Japanese Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Investigators retrospectively collected clinical data at each facility in November 2018 using pre-specified forms.

Results
Based on the biallelic pathogenic variants in ABCB11 and/or no hepatic immunohistochemical detection of BSEP, 14 Japanese PFIC2 patients were enrolled at seven facilities. The median follow-up was 63.2 [47.7–123.3] months. The median age of disease onset was 2.5 [1–4] months. Twelve patients underwent living donor liver transplantation (LDLT), with a median age at LDLT of 9 [4–57] months. Two other patients received sodium 4-phenylbutyrate (NaPB) therapy and survived over 60 months with the native liver. No patients received biliary diversion. The cases that resulted in LDLT had gradually deteriorated growth retardation, biochemical tests, and liver histology since the initial visit. In the other two patients, jaundice, growth retardation, and most of the biochemical tests improved after NaPB therapy was started, but pruritus and liver fibrosis did not.

Conclusions
Japanese PFIC2 patients had gradually worsening clinical findings since the initial visit, resulting in LDLT during infancy. NaPB therapy improved jaundice and growth retardation but was insufficient to treat pruritus and liver fibrosis.
Zero Self-Harm app: a mobile phone application to reduce non-suicidal self-injury—study protocol for a randomized controlled trial
Authors: Guerrero Evelyn , Andreasson Kate , Larsen Lene , Buus Niels , Skovgaard Larsen Jette Louise , Krogh Jesper , Thastum Rasmus , Lindberg Lone , Lindblad Katrine , Erlangsen Annette , Nordentoft Merete 
Published: February 2024

Abstract
Background
Non-suicidal self-injury (NSSI) is a growing healthcare problem. Individuals with NSSI have an increased risk of suicidality. Due to stigma, they may self-injure in secret, which means they might not seek help until events have escalated to include suicidal ideation or a mental disorder. Interventions delivered via mobile phone applications (apps) have been linked to reductions in self-injury. This protocol outlines a trial, which examines whether the Zero Self-Harm intervention, consisting of an app for people with NSSI, can reduce the number of NSSI episodes, suicide ideation, and depressive symptoms.

Methods
The trial will be conducted as a 6-month 2-arm, parallel-group, multicentre, pragmatic, randomized clinical superiority trial. The intervention group will receive the app and instructions on how to use it, while the control group will be allocated to a waitlist and allowed to download the app after 6 months. After inclusion, participants will be asked to complete questionnaires at baseline, 3 months, and 6 months. The primary outcome is the number of NSSI episodes during the preceding month, as measured at the 6 months follow-up with the Deliberate Self-Harm Inventory. A total of 280 participants, 140 in each arm, will be included.

Discussion
This trial will assess the effectiveness of the Zero Self-Harm intervention to reduce the number of NSSI episodes. If effective, the app will have the potential to support a large group of people with NSSI. Considering the stigma related to NSSI, the fact that the app may be used in private and anonymously might make it an appealing and acceptable option for support. The app was developed in collaboration with people with lived experiences related to current and/or previous NSSI. As a result of this, the app focuses on minimizing harm, rather than stopping NSSI. This might enhance its utilization.

Trial registration
ClinicalTrials.gov NCT04463654. Registered on 7 June 2020.
Good Statistical Practice—development of tailored Good Clinical Practice training for statisticians
Authors: Stocken Deborah D. , Mossop Helen , Armstrong Emma , Lewis Steff , Dutton Susan J. , Peckitt Claire , Gamble Carrol , Brown Julia 
Published: February 2024

Abstract
Background
Statisticians are fundamental in ensuring clinical research, including clinical trials, are conducted with quality, transparency, reproducibility and integrity. Good Clinical Practice (GCP) is an international quality standard for the conduct of clinical trials research. Statisticians are required to undertake training on GCP but existing training is generic and, crucially, does not cover statistical activities. This results in statisticians undertaking training mostly unrelated to their role and variation in awareness and implementation of relevant regulatory requirements with regards to statistical conduct. The need for role-relevant training is recognised by the UK NHS Health Research Authority and the Medicines and Healthcare products Regulatory Agency (MHRA).

Methods
The Good Statistical Practice (GCP for Statisticians) project was instigated by the UK Clinical Research Collaboration (UKCRC) Registered Clinical Trials Unit (CTU) Statisticians Operational Group and funded by the National Institute for Health and Care Research (NIHR), to develop materials to enable role-specific GCP training tailored to statisticians. Review of current GCP training was undertaken by survey. Development of training materials were based on MHRA GCP. Critical review and piloting was conducted with UKCRC CTU and NIHR researchers with comment from MHRA. Final review was conducted through the UKCRC CTU Statistics group.

Results
The survey confirmed the need and desire for the development of dedicated GCP training for statisticians. An accessible, comprehensive, piloted training package was developed tailored to statisticians working in clinical research, particularly the clinical trials arena. The training materials cover legislation and guidance for best practice across all clinical trial processes with statistical involvement, including exercises and real-life scenarios to bridge the gap between theory and practice. Comprehensive feedback was incorporated. The training materials are freely available for national and international adoption.

Conclusion
All research staff should have training in GCP yet the training undertaken by most academic statisticians does not cover activities related to their role. The Good Statistical Practice (GCP for Statisticians) project has developed and extensively piloted new, role-specific, comprehensive, accessible GCP training tailored to statisticians working in clinical research, particularly the clinical trials arena. This role-specific training will encourage best practice, leading to transparent and reproducible statistical activity, as required by regulatory authorities and funders.
Effectiveness of structured psycho-oncological counseling for relatives of lung cancer patients based on the CALM approach—study protocol of a randomized controlled trial
Authors: Dusel Julia , Meng Karin , Arnold Hanna , Rabe Antonia , Jentschke Elisabeth 
Published: February 2024

Abstract
Background
The high incidence combined with the high lethality and bad prognosis of lung cancer highlight the need for psycho-oncological care for both patients and their relatives. While psychological interventions for relatives might be helpful, further research on the impact of specific interventions is necessary. Therefore, this trial aims to evaluate structured psycho-oncological counseling for relatives of lung cancer patients based on the Managing Cancer And Living Meaningfully (CALM) approach compared to usual care. In addition, we explore the impact of psycho-oncological support of relatives on the patients’ mental health outcomes.

Methods
The study is a single-center, prospective, randomized controlled trial with two measurement time points. Relatives of lung cancer patients and, thus, the patients themselves (i.e., dyads) are randomly allocated to the intervention group (IG) or the control group (CG) regardless of their disease or treatment stage. Relatives in the IG receive structured counseling based on the CALM approach (three to six sessions with psycho-oncologists). The CG receives usual psycho-oncological care. In addition, cancer patients in both study arms can request psycho-oncological support (usual care) as needed, but they will not get a specific intervention. Relatives and patients complete assessments at baseline (T0) and after the intervention/6 weeks (T1). The primary outcome for relatives is anxiety. Relatives’ secondary outcomes include depressive symptoms, distress, supportive care needs, and quality of life. Patients’ outcomes include anxiety, depression, and distress. All outcomes are assessed using self-report validated questionnaires. Intervention effects will be evaluated using analysis of covariance (ANCOVA) adjusting for baseline values. Power calculations reveal the need to enroll 200 subjects to detect an effect of d = 0.4.

Discussion
The study will provide evidence for the effectiveness of the CALM intervention in relatives of lung cancer patients. Furthermore, study results will contribute to a better understanding of the effectiveness of a psycho-oncological intervention for highly impaired cancer patients and their relatives. If the CALM intervention positively affects the relatives’ psychosocial outcome, it may be implemented in routine care.

Trial registration
German Clinical Trials Register DRKS00030077. Retrospectively registered on 26 October 2022.
Rudi Kundini, Pamoja Kundini (RKPK): study protocol for a hybrid type 1 randomized effectiveness-implementation trial using data science and economic incentive strategies to strengthen the continuity of care among people living with HIV in Tanzania
Authors: Kadota Jillian L. , Packel Laura J. , Mlowe Matilda , Ulenga Nzovu , Mwenda Natalino , Njau Prosper F. , Dow William H. , Wang Jingshen , Sabasaba Amon , McCoy Sandra I. 
Published: February 2024

Abstract
Background
Economic incentives can improve clinical outcomes among in-care people living with HIV (PLHIV), but evidence is limited for their effectiveness among out-of-care PLHIV or those at risk of disengagement. We propose a type 1 hybrid effectiveness-implementation study to advance global knowledge about the use of economic incentives to strengthen the continuity of HIV care and accelerate global goals for HIV epidemic control.

Methods
The Rudi Kundini, Pamoja Kundini study will evaluate two implementation models of an economic incentive strategy for supporting two groups of PLHIV in Tanzania. Phase 1 of the study consists of a two-arm, cluster randomized trial across 32 health facilities to assess the effectiveness of a home visit plus one-time economic incentive on the proportion of out-of-care PLHIV with viral load suppression (< 1000 copies/ml) 6 months after enrollment (n = 640). Phase 2 is an individual 1:1 randomized controlled trial designed to determine the effectiveness of a short-term counseling and economic incentive program offered to in-care PLHIV who are predicted through machine learning to be at risk of disengaging from care on the outcome of viral load suppression at 12 months (n = 692). The program includes up to three incentives conditional upon visit attendance coupled with adapted counselling sessions for this population of PLHIV. Consistent with a hybrid effectiveness-implementation study design, phase 3 is a mixed methods evaluation to explore barriers and facilitators to strategy implementation in phases 1 and 2. Results will be used to guide optimization and scale-up of the incentive strategies, if effective, to the larger population of Tanzanian PLHIV who struggle with continuity of HIV care.

Discussion
Innovative strategies that recognize the dynamic process of lifelong retention in HIV care are urgently needed. Strategies such as conditional economic incentives are a simple and effective method for improving many health outcomes, including those on the HIV continuum. If coupled with other supportive services such as home visits (phase 1) or with tailored counselling (phase 2), economic incentives have the potential to strengthen engagement among the subpopulation of PLHIV who struggle with retention in care and could help to close the gap towards reaching global “95–95-95” goals for ending the AIDS epidemic.

Trial registration
Phase 1: ClinicalTrials.gov, NCT05248100, registered 2/21/2022.
Phase 2: ClinicalTrials.gov, NCT05373095, registered 5/13/2022.