bluuebunny/crossref_metadata_2025 huggingface dataset:
Paramedics’ experiences and observations: work-related emotions and well-being resources during the initial months of the COVID-19 pandemic—a qualitative study
Authors: Myrskykari Henna , Nordquist Hilla
Published: August 2024

Background

As first responders, paramedics are an extremely important part of the care chain. COVID-19 significantly impacted their working circumstances. We examined, according to the experiences and observations of paramedics, (1) what kinds of emotions the Emergency Medical Service (EMS) personnel experienced in their new working circumstances, and (2) what work-related factors became resources for the well-being of EMS personnel during the initial months of the COVID-19 pandemic.

Methods

This qualitative study utilized reflective essay material written by experienced, advanced-level Finnish paramedics (n = 30). The essays used in this study were written during the fall of 2020 and reflected the period when Finland had declared a state of emergency (on 17.3.2020) and the Emergency Powers Act was implemented. The data was analyzed using an inductive thematic analysis.

Results

The emotions experienced by the EMS personnel in their new working circumstances formed three themes: (1) New concerns arose that were constantly present; (2) Surviving without proper guidance; and (3) Rapidly approaching breaking point. Three themes were formed from work-related factors that were identified as resources for the well-being of the EMS personnel. These were: (1) A high level of organizational efficiency was achieved; (2) Adaptable EMS operations; and (3) Encouraging atmosphere.

Conclusions

Crisis management practices should be more attentive to personnel needs, ensuring that managerial and psychological support is readily available in crisis situations. Preparedness that ensures effective organizational adaptation also supports personnel well-being during sudden changes in working circumstances.
Comparing clinical and genomic features based on the tumor location in patients with resected pancreatic cancer
Authors: Yun Won-Gun , Kim Daeun , Lee Mirang , Han Youngmin , Chae Yoon Soo , Jung Hye-Sol , Cho Young Jae , Kwon Wooil , Park Joon Seong , Park Daechan , Jang Jin-Young
Published: August 2024

Background

Pancreatic cancer is anatomically divided into pancreatic head and body/tail cancers, and some studies have reported differences in prognosis. However, whether this discrepancy is induced from the difference of tumor biology is hotly debated. Therefore, we aimed to evaluate the differences in clinical outcomes and tumor biology depending on the tumor location.

Methods

In this retrospective cohort study, we identified 800 patients with pancreatic ductal adenocarcinoma who had undergone upfront curative-intent surgery. Cox regression analysis was performed to explore the prognostic impact of the tumor location. Among them, 153 patients with sufficient tumor tissue and blood samples who provided informed consent for next-generation sequencing were selected as the cohort for genomic analysis.

Results

Out of the 800 patients, 500 (62.5%) had pancreatic head cancer, and 300 (37.5%) had body/tail cancer. Tumor location in the body/tail of the pancreas was not identified as a significant predictor of survival outcomes compared to that in the head in multivariate analysis (hazard ratio, 0.94; 95% confidence interval, 0.77–1.14; P = 0.511). Additionally, in the genomic analyses of 153 patients, there were no significant differences in mutational landscapes, distribution of subtypes based on transcriptomic profiling, and estimated infiltration levels of various immune cells between pancreatic head and body/tail cancers.

Conclusions

We could not find differences in prognosis and tumor biology depending on tumor location in pancreatic ductal adenocarcinoma. Discrepancies in prognosis may represent a combination of lead time, selection bias, and clinical differences, including the surgical burden between tumor sites.
The prognostic value of programmed death-ligand 1 (PD-L1) expression in resected colorectal cancer without neoadjuvant therapy - differences between antibody clones and cell types
Authors: Nobin Hampus , Garvin Stina , Hagman Helga , Nodin Björn , Jirström Karin , Brunnström Hans
Published: August 2024

Background

Programmed death-ligand 1 (PD-L1) expression on tumor cells is associated with poor prognosis in several malignancies, while partly contradictory and inconclusive results have been presented for colorectal cancer (CRC). This study aimed to evaluate PD-L1 as a prognostic biomarker in CRC by comparing three different antibody clones.

Methods

Patients surgically treated for CRC between January 1st, 2007, and December 31st, 2015, in Kalmar County, Sweden, were retrospectively included. Tissue microarrays from 862 primary tumors without neoadjuvant treatment were assessed for immunohistochemical expression of PD-L1 in tumor cells (TC) and immune cells (IC) using clones 73-10, SP263, and 22C3. Cox regression proportional hazard models were used to estimate hazard ratios for overall survival (OS) and disease-free interval (DFI) in univariable and multivariable analyses, with 1% and 5% set as cut-offs for positive expression in TC and IC respectively.

Results

PD-L1 expression in TC was found in 89 (10%) cases for clone 73-10, 76 (9%) for clone SP263, and 38 (4%) for clone 22C3, while the numbers for IC were 317 (37%) cases for clone 73-10, 264 (31%) for clone SP263, and 89 (10%) for clone 22C3. PD-L1 expression in IC was associated with prolonged OS and DFI in univariable analysis for all three clones. The link to prolonged DFI remained in multivariable analysis for 73-10 and SP263, but only for 73-10 regarding OS. PD-L1 expression in TC was not prognostic of OS in any analysis, while it was associated with prolonged DFI for SP263, and a trend was seen for 73-10. The link to prolonged DFI remained for SP263 and was strengthened for 73-10 in multivariable analysis.

Conclusions

The prognostic value of PD-L1 expression in both IC and TC differs between antibody clones, with 73-10 and SP263 being more reliable for prognostic information than 22C3 in resected CRC.
Outcomes of retropupillary iris claw lens implantation in patients with intraocular lens dislocation and low (less than 1000 cells/mm2) corneal endothelial cell density
Authors: Lee Seung Min , Kim Tae Young , Kang Hyun Goo , Lee Junwon , Kim Min
Published: August 2024

Background

Posterior chamber intraocular lens (IOL) dislocation is a common complication of cataract surgery. Dislocated IOLs often require surgical intervention due to the potentially severe risks of leaving this condition untreated. If a patient with extremely low corneal endothelial cell density (ECD) presents with IOL dislocation, the surgeon faces a crucial dilemma of choosing the most optimal surgical treatment option. We sought to investigate the efficacy and safety of retropupillary iris claw intraocular lens (R-IOL) implantation in patients with IOL dislocation and extremely low (< 1000 cells/mm2) ECD.

Methods

We retrospectively reviewed the medical records of nine patients (all men) whose pre-operative ECD was < 1000 cells/mm2and who underwent R-IOL implantation due to intraocular subluxation or total dislocation into the vitreous cavity between 2014 and 2020. We evaluated corneal endothelial function and visual outcomes after surgery.

Results

Nine patients were included in this study. The mean age at diagnosis was 64.89 ± 7.15 years (range 57–76 years), and the follow-up duration was 37.93 ± 23.72 months (range 18.07–89.07 months). No patients developed bullous keratopathy during follow-up. Compared to the initial ECD, corneal thickness (CT), coefficient variation of cell area (CV) and percentage of hexagonal cells (HEX), there was no statistically significant decrease in the ECD, CV, and HEX at last follow-up (P = 0.944, 0.778, 0.445, 0.443). There was significant improvement in the mean uncorrected distance visual acuity (UDVA) at the last follow-up (average 0.13 logMAR, 20/27 Snellen) compared to the pre-operative mean UDVA (average 1.09 logMAR, 20/250 Snellen) (P < 0.01).

Conclusions

R-IOL implantation did not result in a statistically significant decline in corneal endothelial function in patients with preoperatively low ECD, and it significantly improved the mean UDVA postoperatively. R-IOL implantation appears to be a safe and effective treatment modality for intraocular lens dislocation in patients with low ECD (< 1000 cells/mm²); however, long-term follow-up studies are warranted to corroborate these findings.
Public attitudes towards personal health data sharing in long-term epidemiological research: a Citizen Science approach in the KORA study
Authors: Rückert-Eheberg Ina-Maria , Heier Margit , Simon Markus , Kraus Monika , Peters Annette , Linkohr Birgit
Published: August 2024

Background

Loss to follow-up in long-term epidemiological studies is well-known and often substantial. Consequently, there is a risk of bias to the results. The motivation to take part in an epidemiological study can change over time, but the ways to minimize loss to follow-up are not well studied. The Citizen Science approach offers researchers to engage in direct discussions with study participants and to integrate their opinions and requirements into cohort management.

Methods

Guided group discussions were conducted with study participants from the KORA cohort in the Augsburg Region in Germany, established 40 years ago, as well as a group of independently selected citizens. The aim was to look at the relevant aspects of health studies with a focus on long-term participation. A two-sided questionnaire was developed subsequently in a co-creation process and presented to 500 KORA participants and 2,400 employees of the research facility Helmholtz Munich.

Results

The discussions revealed that altruistic motivations, (i.e. supporting research and public health), personal benefits (i.e. a health check-up during a study examination), data protection, and information about research results in layman’s terms were crucial to ensure interest and long-term study participation. The results of the questionnaire confirmed these aspects and showed that exclusively digital information channels may be an obstacle for older and less educated people. Thus, paper-based media such as newsletters are still important.

Conclusions

The findings shed light on cohort management and long-term engagement with study participants. A long-term health study needs to benefit public and individual health; the institution needs to be trustworthy; and the results and their impact need to be disseminated in widely understandable terms and by the right means of communication back to the participants.
Health care needs and barriers to care among the transgender population: a study from western Rajasthan
Authors: Ahuja Tanvi Kaur , Goel Akhil Dhanesh , Gupta Manoj Kumar , Joshi Nitin , Choudhary Annu , Suman Swati , Taluja Kajal , Mittal Madhukar , Ghuman Navdeep Kaur , Suthar Navratan , Bhardwaj Pankaj
Published: August 2024

Background

Transgender people comprise an estimated 0.3–0.5% (25 million) of the global population. The public health agenda focuses on understanding and improving the health and well-being of gender minorities. Transgender (TG) persons often have complex healthcare needs and suffer significant health disparities in multiple arenas. The international literature suggests that this community is at a higher risk of depression, and other mental health problems, including HIV. Many transgender people experience gender dysphoria and seek specific medical needs such as sex reassignment surgeries, implants, hormonal therapies, etc., but are unable to access these services due to financial or social reasons. The objective of this study was to assess the healthcare needs and associated barriers experienced by transgender people in Western Rajasthan. Methodology: A qualitative study was carried out in which multilevel stakeholder interviews were conducted using interview and focus group discussion guides. Data was analyzed using the qualitative thematic analysis technique. Results: Findings reveal that transgender people have expressed their need to access health services for general health needs, including but not limited to mental health, non-communicable diseases, and infectious diseases. Barriers to healthcare services were identified on 3 levels: health system, social and personal. Health system barriers include policy, accessibility, affordability, and acceptability issues. Social factors such as inadequate housing, education, and job opportunities also play an important role in affecting the individual’s health-seeking behavior. The knowledge of healthcare providers in this context was also limited in context of health insurance schemes, package of services available for transgenders and the importance of gender sensitive healthcare. Conclusion: Transgender people expressed the need for mental health services, programs targeting nutritional improvement, gender-affirmation procedures besides regular screening of non-communicable diseases as operational for males and females. Levels of barriers have been identified at various levels ranging from absence of targeted policies to individual behavior.
Parent and healthcare professional experiences of critical congenital heart disease in New Zealand to advance health equity
Authors: Watkins Simone , Ward Kim , Brown Rachel , Crengle Sue , WM de Laat Monique , Percival Teuila , Sadler Lynn , Cloete Elza , Gorinski Ruth , Gentles Thomas , Bloomfield Frank H.
Published: August 2024

Background

Higher odds of survival have been reported in European infants compared to Indigenous Māori and Pasifika infants with critical congenital heart disease in New Zealand. We therefore aimed to understand how to mitigate this disparity by investigating the parent and healthcare professional experiences’ of critical congenital heart disease healthcare in New Zealand.

Methods

A prospective qualitative study utilising semi-structured interviews was conducted on a cohort of purposefully sampled parents and health professionals with experience of critical congenital heart disease healthcare in New Zealand. Parents were recruited after a fetal critical congenital heart disease diagnosis and offered two interviews at least three months apart, whilst multidisciplinary fetal and cardiosurgical health professionals were interviewed once. Interviews were recorded and transcribed verbatim before coding, categorization and qualitative analysis.

Results

During 2022 and 2023, 45 people participated in 57 interviews (25 parents: 19 mothers, 6 fathers; Indigenous Māori, n = 5; Pasifika, n = 6; Asian, n = 4; European, n = 10; and 20 healthcare professionals: European n = 17). The three lessons learned from participants were: (1) Minoritized groups experience disparate healthcare quality; (2) healthcare systems are under-resourced to provide equitable support for the differential needs of grieving parents; and (3) healthcare systems could engage minoritized families more optimally in shared decision-making.

Conclusions

According to the experiences of parents and healthcare professionals, persisting inequities in CCHD healthcare quality occur by ethnic group, with the New Zealand healthcare system privileging European families. The concepts from this study could be translated by healthcare leaders, policymakers, and professionals into evidence-based healthcare system improvements to enhance experiences for non-European families more broadly.
Identification of mothers with mental health problems is accidental: perceptions of health care providers on availability, access, and support for maternal mental health care for adolescent mothers in Malawi
Authors: Tembo Chimwemwe , Portsmouth Linda , Burns Sharyn
Published: August 2024

Background

Integration of maternal mental health into primary health care is considered a strategy to improve access to mental health support in low- and middle-income countries (LMICs). Health care workers’ (HCWs) and traditional practitioners’ (traditional healers, herbalists, traditional birth attendants, spiritual healers, prophets, and community health volunteers) perceptions of the availability and management of adolescent mothers’ maternal mental health care were explored in rural Malawi. Recognizing and identifying the barriers associated with access to maternal mental health support is essential to improving the mental health of adolescent mothers.

Methods

A descriptive qualitative design (DQ) was used to explore HCWs’ and traditional practitioners’ perceptions of maternal mental health services for adolescent mothers. In-depth interviews were conducted with HCWs (n = 6), and three focus group discussions were conducted with 30 community-based traditional practitioners. Participants were purposefully recruited because they provide formal or informal health services to adolescent mothers during the postnatal period at Mitundu Rural Hospital and its catchment area in Lilongwe District, in Malawi. Interviews were analyzed using reflective thematic analysis and inductive thinking.

Results

Thematic analysis found four themes to describe access to maternal mental health care for adolescent mothers. Participant perceptions were themed around health system challenges and how cultural background and beliefs influence access to mental health care and support. The themes were: (1) Inadequate staff development; (2) Limited resources (medication and infrastructure); (3) Limited policy and guidelines implementation; and (4) Cultural background and belief influence on help-seeking. HCWs suggested improving pre-service and in-service training to improve mental health assessment of mothers, while traditional practitioners wanted to increase their awareness of mental health issues.

Conclusion

Participants emphasized that multifaceted factors influenced access to mental health support. These factors affect the assessment, treatment, and support of adolescent mothers and help-seeking by mothers. Therefore, strengthening the healthcare system and empowering providers with the knowledge and skills to recognize at-risk mothers and provide timely support is essential.
Inter-laboratory comparison of eleven quantitative or digital PCR assays for detection of proviral bovine leukemia virus in blood samples
Authors: Pluta Aneta , Jaworski Juan Pablo , Droscha Casey , VanderWeele Sophie , Taxis Tasia M. , Valas Stephen , Brnić Dragan , Jungić Andreja , Ruano María José , Sánchez Azucena , Murakami Kenji , Nakamura Kurumi , Puentes Rodrigo , De Brun MLaureana , Ruiz Vanesa , Gómez Marla Eliana Ladera , Lendez Pamela , Dolcini Guillermina , Camargos Marcelo Fernandes , Fonseca Antônio , Barua Subarna , Wang Chengming , Giza Aleksandra , Kuźmak Jacek
Published: August 2024

Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis and causes a persistent infection that can leave cattle with no symptoms. Many countries have been able to successfully eradicate BLV through improved detection and management methods. However, with the increasing novel molecular detection methods there have been few efforts to standardize these results at global scale. This study aimed to determine the interlaboratory accuracy and agreement of 11 molecular tests in detecting BLV. Each qPCR/ddPCR method varied by target gene, primer design, DNA input and chemistries. DNA samples were extracted from blood of BLV-seropositive cattle and lyophilized to grant a better preservation during shipping to all participants around the globe. Twenty nine out of 44 samples were correctly identified by the 11 labs and all methods exhibited a diagnostic sensitivity between 74 and 100%. Agreement amongst different assays was linked to BLV copy numbers present in samples and the characteristics of each assay (i.e., BLV target sequence). Finally, the mean correlation value for all assays was within the range of strong correlation. This study highlights the importance of continuous need for standardization and harmonization amongst assays and the different participants. The results underscore the need of an international calibrator to estimate the efficiency (standard curve) of the different assays and improve quantitation accuracy. Additionally, this will inform future participants about the variability associated with emerging chemistries, methods, and technologies used to study BLV. Altogether, by improving tests performance worldwide it will positively aid in the eradication efforts.
The diagnostic performance of CA-125 for the detection of ovarian cancer in women from different ethnic groups: a cohort study of English primary care data
Authors: Barlow Melissa , Down Liz , Mounce Luke T. A. , Funston Garth , Merriel Samuel W. D. , Watson Jessica , Abel Gary , Kirkland Lucy , Martins Tanimola , Bailey Sarah E. R.
Published: August 2024

Background

CA-125 testing is a recommended first line investigation for women presenting with possible symptoms of ovarian cancer in English primary care, to help determine whether further investigation for ovarian cancer is needed. It is currently not known how well the CA-125 test performs in ovarian cancer detection for patients from different ethnic groups.

Methods

A retrospective cohort study utilising English primary care data linked to the national cancer registry was undertaken. Women aged ≥ 40 years with a CA-125 test between 2010 and 2017 were included. Logistic regression predicted one-year ovarian cancer incidence by ethnicity, adjusting for age, deprivation status, and comorbidity score. The estimated incidence of ovarian cancer by CA-125 level was modelled for each ethnic group using restricted cubic splines.

Results

The diagnostic performance of CA-125 differed for women from different ethnicities. In an unadjusted analysis, predicted CA-125 levels for Asian and Black women were higher than White women at corresponding probabilities of ovarian cancer. The higher PPVs for White women compared to Asian or Black women were eliminated by inclusion of covariates.

Conclusion

The introduction of ethnicity-specific thresholds may increase the specificity and PPVs of CA-125 in ovarian cancer detection at the expense of sensitivity, particularly for Asian and Black women. As such, we cannot recommend the use of ethnicity-specific thresholds for CA-125.
Biallelic NEXN variants and fetal onset dilated cardiomyopathy: two independent case reports and revision of literature
Authors: Picciolli Irene , Ratti Angelo , Rinaldi Berardo , Baban Anwar , Iascone Maria , Francescato Gaia , Cappelleri Alessia , Magliozzi Monia , Novelli Antonio , Parlapiano Giovanni , Colli Anna Maria , Persico Nicola , Carugo Stefano , Mosca Fabio , Bedeschi Maria Francesca
Published: August 2024

Background

Dilated cardiomyopathy (DCM) is an etiologically heterogeneous group of diseases of the myocardium. With the rapid evolution in laboratory investigations, genetic background is increasingly determined including many genes with variable penetrance and expressivity. Biallelic NEXN variants are rare in humans and associated with poor prognosis: fetal and perinatal death or severe DCMs in infants.

Case presentation

We describe two male infants with prenatal diagnosis of dilated cardiomyopathy with impaired ventricular contractility. One of the patients showed hydrops and polyhydramnios. Postnatally, a DCM with severely reduced systolic function was confirmed and required medical treatment. In patient 1, Whole Exome Sequencing (WES) revealed a homozygous NEXN variant: c.1156dup (p.Met386fs) while in patient 2 a custom Next Generation Sequencing (NGS) panel revealed the homozygous NEXN variant c.1579_1584delp. (Glu527_Glu528del). These NEXN variants have not been previously described. Unlike the unfavorable prognosis described for biallelic NEXN variants, we observed in both our patients a favorable clinical course over time.

Conclusion

This report might help to broaden the present knowledge regarding NEXN biallelic variants and their clinical expression. It might be worthy to consider the inclusion of the NEXN gene sequencing in the investigation of pediatric patients with DCM.
Health information literacy among children with spinal muscular atrophy and their caregivers
Authors: Zhang Weiran , Feng Yijie , Yan Yue , Yao Mei , Gao Feng , Lin Wei , Mao Shanshan
Published: August 2024

Background

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease that leads to multiple organ dysfunction. The advent of disease-modifying treatments makes the early diagnosis of SMA critical. Health information literacy is vital for obtaining, understanding, screening, and using health information. Considering the importance of early diagnosis and the challenges in obtaining accurate information on patients with SMA, this cross-sectional study assessed health information literacy among children with SMA and their caregivers in China.

Methods

Interviews with the caregivers of 10 patients with SMA were conducted by neurologists specializing in SMA. A questionnaire for evaluating the level of health information literacy was further developed among 145 children with SMA aged 10.0–120.0 months, with the average age of 81.9 months, and their caregivers. Parameters, such as the age at the onset of the first symptom and time from recognition of the first symptom to diagnosis, were examined. Health information literacy was measured using four dimensions: cognition, search, evaluation, and application.

Results

The average time from the first symptom to first medical consultation was 4.8 months, and that from the first symptom to diagnosis was 10.8 months. There is a significant delay from the onset of the initial symptoms to a definitive diagnosis. Thirty-five (24%) patients had poor while 26 (18%) had high health information literacy. The overall score for health information literacy was 69; the scores for health information cognition and application were 90 and 84, respectively. The scores for evaluation (61) and search (57) were low. Medical personnel were considered the most professional and credible sources of information. Additionally, search engines and patient organizations were the other two most important sources of health literacy.

Conclusion

Patients with SMA and their caregivers had low levels of health information literacy. SMA information visibility and standardization need to be improved. Medical personnel with experience in the diagnosis and treatment of SMA and media should aim to share knowledge and increase the quality of life of those with SMA.
Clinical characteristics and long-term outcome of CASPR2 antibody-associated autoimmune encephalitis in children
Authors: Liao Donglei , Zhu Saying , Yang Lifen , Zhang Ciliu , He Fang , Yin Fei , Peng Jing
Published: August 2024

Background

Contactin-associated protein-2(CASPR2) antibody-associated autoimmune encephalitis(AE) is rare in children. This study aimed to report the clinical characteristics and long-term outcome of CASPR2 autoimmunity in children to expand the disease spectrum.

Methods

Children who were hospitalized in our hospital with clinically suspected AE from May 2015 to April 2022 and underwent neuronal surface antibodies detections were retrospectively analyzed. Clinical data of patients with CASPR2 autoimmunity were collected.

Results

Patients who were positive for NMDAR-IgG, CASPR2-IgG, LGI1-IgG and IgLON5-IgG occupied 95.2%(119/125),3.2%(4/125),0.8%(1/125) and 0.8%(1/125), respectively.The median onset age of the 4 patients with CASPR2-IgG was 5.6 years. The most common symptoms were psychiatric symptoms/abnormal behavior(3/4) and sleep dysfunction(3/4). One patient developed a phenotype of Rasmussen encephalitis(RE). Tumor was absent in our patients. Two patients showed abnormal findings on initial brain magnetic resonance imaging(MRI) scans. All the patients showed favorable response to immunotherapy except the patient with RE experienced recurrent symptoms who finally achieved remission after surgery. All the patients had a favorable long-term outcome at the last follow-up(33-58months).

Conclusions

CASPR2 autoimmunity may be the second most common anti-neuronal surface antibodies associated neurological disease in children. Psychiatric symptoms/abnormal behavior and sleep disorder were common in children with CASPR2-associated AE. Tumor was rare in those patients. Most pediatric patients had a favorable long-term outcome.
Different radiomics annotation methods comparison in rectal cancer characterisation and prognosis prediction: a two-centre study
Authors: Zhu Ying , Wei Yaru , Chen Zhongwei , Li Xiang , Zhang Shiwei , Wen Caiyun , Cao Guoquan , Zhou Jiejie , Wang Meihao
Published: August 2024

Objectives

To explore the performance differences of multiple annotations in radiomics analysis and provide a reference for tumour annotation in large-scale medical image analysis.

Methods

A total of 342 patients from two centres who underwent radical resection for rectal cancer were retrospectively studied and divided into training, internal validation, and external validation cohorts. Three predictive tasks of tumour T-stage (pT), lymph node metastasis (pLNM), and disease-free survival (pDFS) were performed. Twelve radiomics models were constructed using Lasso-Logistic or Lasso-Cox to evaluate and four annotation methods, 2D detailed annotation along tumour boundaries (2D), 3D detailed annotation along tumour boundaries (3D), 2D bounding box (2DBB), and 3D bounding box (3DBB) on T2-weighted images, were compared. Radiomics models were used to establish combined models incorporating clinical risk factors. The DeLong test was performed to compare the performance of models using the receiver operating characteristic curves.

Results

For radiomics models, the area under the curve values ranged from 0.627 (0.518–0.728) to 0.811 (0.705–0.917) in the internal validation cohort and from 0.619 (0.469–0.754) to 0.824 (0.689–0.918) in the external validation cohort. Most radiomics models based on four annotations did not differ significantly, except between the 3D and 3DBB models for pLNM (p = 0.0188) in the internal validation cohort. For combined models, only the 2D model significantly differed from the 2DBB (p = 0.0372) and 3D models (p = 0.0380) for pDFS.

Conclusion

Radiomics and combined models constructed with 2D and bounding box annotations showed comparable performances to those with 3D and detailed annotations along tumour boundaries in rectal cancer characterisation and prognosis prediction.

Critical relevance statement

For quantitative analysis of radiological images, the selection of 2D maximum tumour area or bounding box annotation is as representative and easy to operate as 3D whole tumour or detailed annotations along tumour boundaries.

Key Points

There is currently a lack of discussion on whether different annotation efforts in radiomics are predictively representative.

No significant differences were observed in radiomics and combined models regardless of the annotations (2D, 3D, detailed, or bounding box).

Prioritise selecting the more time and effort-saving 2D maximum area bounding box annotation.

Graphical Abstract
Salivary gland organoid transplantation as a therapeutic option for radiation-induced xerostomia
Authors: Jeon Seong Gyeong , Lee Jaeseon , Lee Su Jeong , Seo Jaehwi , Choi Jinkyoung , Bae Dong Hyuck , Chun Duk-Hee , Ko Seung Young , Shin Hyun Soo , Joo Lina , Lee Sang-Hyuk , Lim Young Chang , Choi Woo Hee , Yoo Jongman
Published: August 2024

Background

Xerostomia is a pathological condition characterized by decreased salivation due to salivary gland dysfunction and is frequently attributed to irreversible damage as a side effect of radiation therapy. Stem cell–derived organoid therapy has garnered attention as a promising avenue for resolving this issue. However, Matrigel, a hydrogel commonly used in organoid culture, is considered inappropriate for clinical use due to its undefined composition and immunogenicity. In this study, we aimed to develop a method for culturing collagen-based human salivary gland organoids (hSGOs) suitable for clinical applications and evaluated their therapeutic effectiveness.

Methods

Human salivary gland stem cells were isolated from the salivary gland tissues and cultured in both Matrigel and collagen. We compared the gene and protein expression patterns of salivary gland–specific markers and measured amylase activity in the two types of hSGOs. To evaluate the therapeutic effects, we performed xenogeneic and allogeneic transplantation using human and mouse salivary gland organoids (hSGOs and mSGOs), respectively, in a mouse model of radiation-induced xerostomia.

Results

hSGOs cultured in Matrigel exhibited self-renewal capacity and differentiated into acinar and ductal cell lineages. In collagen, they maintained a comparable self-renewal ability and more closely replicated the characteristics of salivary gland tissue following differentiation. Upon xenotransplantation of collagen-based hSGOs, we observed engraftment, which was verified by detecting human-specific nucleoli and E-cadherin expression. The expression of mucins, especially MUC5B, within the transplanted hSGOs suggested a potential improvement in the salivary composition. Moreover, the allograft procedure using mSGOs led to increased salivation, validating the efficacy of our approach.

Conclusions

This study showed that collagen-based hSGOs can be used appropriately in clinical settings and demonstrated the effectiveness of an allograft procedure. Our research has laid the groundwork for the future application of collagen-based hSGOs in allogeneic clinical trials.
KCNJ16-depleted kidney organoids recapitulate tubulopathy and lipid recovery upon statins treatment
Authors: Sendino Garví E. , van Slobbe G. J. J. , Zaal E. A. , de Baaij J. H. F. , Hoenderop J. G. , Masereeuw R. , Janssen M. J. , van Genderen A. M.
Published: August 2024

Background

The KCNJ16 gene has been associated with a novel kidney tubulopathy phenotype, viz. disturbed acid–base homeostasis, hypokalemia and altered renal salt transport. KCNJ16 encodes for Kir5.1, which together with Kir4.1 constitutes a potassium channel located at kidney tubular cell basolateral membranes. Preclinical studies provided mechanistic links between Kir5.1 and tubulopathy, however, the disease pathology remains poorly understood. Here, we aimed at generating and characterizing a novel advanced in vitro human kidney model that recapitulates the disease phenotype to investigate further the pathophysiological mechanisms underlying the tubulopathy and potential therapeutic interventions.

Methods

We used CRISPR/Cas9 to generate KCNJ16 mutant (KCNJ16+/− and KCNJ16−/−) cell lines from healthy human induced pluripotent stem cells (iPSC) KCNJ16 control (KCNJ16WT). The iPSCs were differentiated following an optimized protocol into kidney organoids in an air–liquid interface.

Results

KCNJ16-depleted kidney organoids showed transcriptomic and potential functional impairment of key voltage-dependent electrolyte and water-balance transporters. We observed cysts formation, lipid droplet accumulation and fibrosis upon Kir5.1 function loss. Furthermore, a large scale, glutamine tracer flux metabolomics analysis demonstrated that KCNJ16−/− organoids display TCA cycle and lipid metabolism impairments. Drug screening revealed that treatment with statins, particularly the combination of simvastatin and C75, prevented lipid droplet accumulation and collagen-I deposition in KCNJ16−/− kidney organoids.

Conclusions

Mature kidney organoids represent a relevant in vitro model for investigating the function of Kir5.1. We discovered novel molecular targets for this genetic tubulopathy and identified statins as a potential therapeutic strategy for KCNJ16 defects in the kidney.
Oncological characteristics, treatments and prognostic outcomes in MMR-deficient colorectal cancer
Authors: Fan Wen-Xuan , Su Fei , Zhang Yan , Zhang Xiao-Ling , Du Yun-Yi , Gao Yang-Jun , Li Wei-Ling , Hu Wen-Qing , Zhao Jun
Published: August 2024

Colorectal cancer (CRC) ranks as the third most prevalent cancer globally. It’s recognized that the molecular subtype of CRC, characterized by mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H), plays a critical role in determining appropriate treatment strategies. This review examines the current molecular classifications, focusing on dMMR/MSI-H CRC and its subtypes: Lynch syndrome (LS), Lynch-like syndrome (LLS), and sporadic cases. Despite advances in understanding of these genetic backgrounds, clinical trials have not conclusively differentiated the efficacy of immune checkpoint inhibitors among these subgroups. Therefore, while this review details the molecular characteristics and their general implications for treatment and prognosis, it also highlights the limitations and the need for more refined clinical studies to ascertain tailored therapeutic strategies for each subtype. Furthermore, this review summarizes completed and ongoing clinical studies, emphasizing the importance of developing treatments aligned more closely with molecular profiles. By discussing these aspects, the review seeks to provide a comprehensive analysis of oncological characteristics, presenting a detailed understanding of their implications for treatment and prognosis in dMMR/MSI-H CRC.
Comparative long-term outcomes of vitrectomy combined with anterior chamber intraocular lens to intra-scleral haptic fixation of posterior chamber intraocular lens
Authors: Warren Alexis , Kemp Pavlina S. , Coussa Razek G. , Cheng Liang , Boldt H. Culver , Russell Stephen R. , Johnson A. Tim , Oetting Thomas A. , Sohn Elliott H.
Published: August 2024

Purpose

To evaluate the long-term clinical outcomes in patients with combined pars plana vitrectomy (PPV) with anterior chamber intraocular lens (ACIOL) to intrascleral haptic fixation (ISHF) using the Agarwal technique with fibrin glue to secure the scleral flap of a posterior chamber intraocular lens.

Methods

Retrospective, consecutive, single-center, comparative case series. 83 eyes were studied. Patients with < 8 months of follow-up were excluded. Detailed pre-, intra-, and post-operative complications were analyzed using mixed model univariate analysis and t-test. Pre- and post-operative best corrected visual acuity (BCVA) was analyzed.

Results

Twenty-five subjects met entry criteria. Mean age at time of surgery was 70.4 ± 17.7 years in the ACIOL group (n = 12) and 54.6 ± 21.1 years in the ISHF group (n = 13; p = 0.03). Mean follow-up was 38.2 months. Incidence of corneal decompensation was similar in the ACIOL and ISHF lens group (p = 0.93). There was no difference in the BCVA mean change or cystoid macular edema (CME) at the final visit between the groups (p = 0.47; p = 0.08), but there was a trend toward increased CME in the ACIOL group.

Conclusions

PPV with concomitant placement of either ACIOL or ISHF lens result in improvement in BCVA. Both procedures are well tolerated and result in favorable outcomes with long-term follow-up though varying patient populations do not allow precise comparison between the two groups.
Non-invasive hemodynamic monitoring during initiation of positive airway pressure treatment in patients with obstructive sleep apnea: a feasibility study
Authors: Müller Christoph , Kerl Jens , Dellweg Dominic
Published: August 2024

Background

The association of obstructive sleep apnea (OSA) with cardiovascular morbidity has been repeatedly reported in numerous studies and argues for treatment initiation even in the absence of significant day time sleepiness. While the long-term consequences of positive airway pressure (PAP) treatment on OSA related comorbidities like secondary hypertension are based on substantial clinical evidence, less is known about the immediate hemodynamic effects.

Methods

This study tried to investigate the impact of PAP treatment on different hemodynamic parameters in 48 patients with OSA by extending the standard polysomnographic assessment with non-invasive hemodynamic monitoring using impedance cardiography (ICG). On two consecutive nights under diagnostic and therapeutic conditions, polysomnographic and hemodynamic data were acquired. In addition, we subdivided the participants according to their treatment related change in stroke volume (SV) and assigned the hemodynamic measurements to the corresponding sleep stage.

Results

Comparing both conditions, a non-statistically significant decrease in SV and cardiac output (CO) was observed for all participants. Treatment initiation was associated with a statistically significant prolongation of the pre-ejection period (PEP) for the entire study population (p = 0.001) and the subgroup with decreasing SV (p = 0.008). In addition, systolic blood pressure (SBP) (p = 0.026) and pulse pressure (PP) (p = 0.041) were lowered significantly for patients with a therapeutically reduced SV under treatment conditions. A higher BMI (p = 0.020) and a more pronounced reduction of the respiratory distress index (RDI) (p = 0.030) and the arousal-index (p = 0.021) were observed for patients with decreasing SV. Correlational analysis revealed a negative relationship between the diagnostic values for both SBP (r=-0.324, p = 0.025) and PP (r=-0.407, p = 0.004) with the change in SV and a positive correlation with the change of the SBP (r = 0.317, p = 0.028) for all participants.

Conclusions

To conclude, our results indicate that treatment with a PAP device in patients with OSA can lead to a decrease in SV which is associated with a lowering of the SBP. This may be caused by a reduced sympathetic tone due to less respiratory events and an improved sleep profile.
Protective effect of β-sitosterol against high-fructose diet-induced oxidative stress, and hepatorenal derangements in growing female sprague-dawley rats
Authors: Gumede Nontobeko M. , Lembede Busisani W. , Nkomozepi Pilani , Brooksbank Richard L. , Erlwanger Kennedy H. , Chivandi Eliton
Published: August 2024

Background

Chronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed.

Results

High fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman’s capsule area and urinary space. β-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function.

Conclusions

β-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury.
TROPHY-U-01 Cohort 2: A Phase II Study of Sacituzumab Govitecan in Cisplatin-Ineligible Patients With Metastatic Urothelial Cancer Progressing After Previous Checkpoint Inhibitor Therapy
Authors: Petrylak Daniel P. , Tagawa Scott T. , Jain Rohit K. , Bupathi Manojkumar , Balar Arjun , Kalebasty Arash Rezazadeh , George Saby , Palmbos Phillip , Nordquist Luke , Davis Nancy , Ramamurthy Chethan , Sternberg Cora N. , Loriot Yohann , Agarwal Neeraj , Park Chandler , Tonelli Julia , Vance Morganna , Zhou Huafeng , Grivas Petros , Petrylak Daniel P. , Tagawa Scott T. , Jain Rohit K. , Bupathi Manojkumar , Balar Arjun , Kalebasty Arash Rezazadeh , George Saby , Palmbos Phillip , Nordquist Luke , Davis Nancy , Ramamurthy Chethan , Sternberg Cora N. , Agarwal Neeraj , Park Chandler , Tonelli Julia , Vance Morganna , Zhou Huafeng , Grivas Petros , Loriot Yohann
Published: August 2024

PURPOSE

Sacituzumab govitecan (SG) is a Trop-2–directed antibody-drug conjugate with an SN-38 payload, approved for patients with locally advanced (LA) or metastatic urothelial cancer (mUC) who progressed after platinum (PT)-based chemotherapy and a checkpoint inhibitor (CPI). Here, we report results from Cohort 2 of TROPHY-U-01 trial, evaluating the efficacy and safety of SG in patients with mUC.

METHODS

TROPHY-U-01 (ClinicalTrials.gov identifier:
NCT03547973
) is a multicohort, open-label phase II study. Cohort 2 includes patients with LA or mUC who have had progression or recurrence after a CPI and were cisplatin-ineligible at study initiation. Patients received SG 10 mg/kg on days 1 and 8 of 21-day cycles. The primary end point was objective response rate (ORR) per central review; secondary end points were clinical benefit rate (CBR), duration of response (DOR), and progression-free survival (PFS) per central review and safety.

RESULTS

Cohort 2 included 38 patients (61% male; median age 72.5 years; 66% visceral metastases [29% liver]; 50% received previous PT-based chemotherapy as previous [neo]adjuvant therapy]). At a median follow-up of 9.3 months, ORR was 32% (95% CI, 17.5 to 48.7), CBR 42% (95% CI, 26.3 to 59.2), median DOR 5.6 months (95% CI, 2.8 to 13.3), median PFS 5.6 months (95% CI, 4.1 to 8.3), and median overall survival 13.5 months (95% CI, 7.6 to 15.6). Grade ≥3 treatment-emergent adverse events occurred in 87% of patients, most commonly neutropenia (34%), anemia (24%), leukopenia (19%), fatigue (18%), and diarrhea (16%).

CONCLUSION

SG monotherapy demonstrated a relatively high ORR with rapid responses; this was feasible with a manageable toxicity profile in cisplatin-ineligible patients who had progression after CPI therapy. Limitations include a moderate sample size and lack of random assignment. These results warrant further evaluation of SG alone and in combinations in patients with LA/mUC.
All of Us or None
Authors: Das Gupta Monisha
Published: August 2024

In All of Us or None, Monisha Das Gupta tells the story of contemporary antideportation organizing in the United States by migrants and refugees labeled as criminal aliens. These activists, who live daily with criminalization, work against forms of deportation that Das Gupta calls settler carcerality—the United States’ use of deportation to exert territorial control in the face of Indigenous self-determination. Drawing on fieldwork with antideportation organizing groups in New York, Los Angeles, Long Beach, and Honolulu, Das Gupta documents the inventive methods of struggle against settler carcerality. Das Gupta shows how the organizers’ actions and visions depart from the settler colonial nature of the mainstream demands for a pathway to citizenship and civil rights. Through direct action, storytelling, political education, and youth and queer leadership, these organizations and collectives conceptualize an abolitionist vision of migration justice that rejects the settler state and encompasses all those who are disavowed. By highlighting this work, Das Gupta demonstrates the transformative promise offered by a dissident migrant-led politics working toward dismantling settler structures and logics.