bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-infiltrating T-Lymphocyte immunity-related immune tolerance and anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy for advanced hepatocellular carcinoma
Authors: Hu Lingzhen , Wang Zongren , Liao Yang , Jiang Xiaomeng , Lian Huojun , Lin Zhuoying 
Published: August 2024

AbstractSystemic therapy has become the standard treatment for patients with advanced hepatocellular carcinoma (HCC) whose treatment options are limited. However, the long-term patient response to drugs and the survival outcomes remain a concern. With increasing exploration of the HCC microenvironment, particularly in terms of T lymphocyte immunity, a new era of immunomolecular targeted therapy, based on molecular signaling, has arrived for advanced HCC. In the study of immune tolerance of the intrinsic HCC microenvironment, we found that multiple immunosuppressive mechanisms and immune checkpoint inhibitors, such as anti–programmed cell death protein 1/ligand of programmed cell death protein 1 therapy, have improved clinical outcomes in some patients with advanced HCC. Furthermore, various combination therapies have been investigated, and HCC types have been categorized into different types based on anti–programmed cell death protein 1 (PD-1)/ligand of programmed cell death protein 1 (PD-L1) treatment. In this paper, we first discuss the tumor-infiltrating T lymphocyte immunity and immune tolerance of HCC. We then clarify the basic mechanism of anti–PD-1/PD-L1 therapy and discuss the types of HCC based on anti–PD-1/PD-L1 therapy. Thereafter, we explain the relevant studies and mechanisms of combination therapy of anti–PD-1/PD-L1 with antiangiogenesis drugs or multikinase kinase inhibitors, anti–T lymphocyte–related signaling pathways in HCC, and other anti-CD8+T cell immune checkpoints. In this way, this review offers a deeper understanding of anti–PD-1/PD-L1 immunotherapy for advanced HCC, in order to provide better individualized treatments for patients with advanced HCC.
Studies on surgical methods for sporadic micromedullary thyroid carcinoma
Authors: Ni Yaqiong , Hou Xiaofeng , Yao Wei , Wang Tao , Liu Qinjiang 
Published: August 2024

Abstract

Background
To observe the changes in serum calcitonin levels after application of different surgical methods for primary medullary thyroid microcarcinoma (MTMC) and explore a more reasonable surgical method.

Methods
A retrospective analysis of 36 patients with MTMC, 16 in group A and 20 in group B, was performed. In group A, tumors were single and confined to the thyroid lobe, and thyroid lobectomy with isthmusectomy was performed. In group B, tumors were in the isthmus or invaded the thyroid gland, or there were multiple foci in bilateral lobes, and patients with primary foci underwent total thyroidectomy. The median follow-up time was 3.6 years. Clinical and pathological characteristics and changes in serum calcitonin (CTn) and carcinoembryonic antigen levels after the surgery were compared between the 2 groups.

Results
The difference in the biochemical cure rate after surgery was statistically significant between patients with preoperative serum calcitonin levels <150 pg/mL and ≥150 pg/mL (P < 0.01). No significant differences in the biochemical cure rates and serum calcitonin levels were noted at different time points after surgery between group A and group B (P > 0.05). One recurrence and metastasis were observed in each group after surgery.

Conclusions
After performing different surgical methods for the primary foci of MTMC, the changes in serum calcitonin and carcinoembryonic antigen levels are similar. Especially for patients with single foci confined to the thyroid lobe without lateral cervical lymph node metastasis and with serum calcitonin levels <150 pg/mL, the unilateral thyroid lobectomy with isthmectomy can achieve the same therapeutic effect and biochemical cure rate as total thyroidectomy.
Perceptions of telemedicine amongst physical medicine and rehabilitation patients and healthcare providers
Authors: Gilmer Gabrielle , Sowa Gwendolyn 
Published: August 2024

Abstract

Objective
Our purpose was to assess perceptions of telemedicine amongst physical medicine & rehabilitation (PM&R) patients and healthcare providers.

Design
A 28-question online survey was conducted. Patients had to be 18 years or older who used telemedicine for a PM&R visit. Providers had to be a board-certified PM&R provider who has used telemedicine in their practice.

Results
Sixty-eight patients and forty-six providers completed the survey. Patients and providers reported an intention to continue using telemedicine, regardless of insurance coverage/reimbursement. Patients and providers reported circumstances, such as needing a physical examination or a first-time visit, as being preferable for an in-person visit. Patients who were younger or a caretaker were more likely to report being willing to change providers if telemedicine was no longer offered than older or non-caretaker patients. Patients who made less than $30,000 annually or who did not own a car were more likely to report comfortability with telemedicine than patients who made more than $30,000 annually or who owned a car.

Conclusion
Telemedicine will continue as a staple of PM&R healthcare and is a particularly important resource for patients who are younger, caretakers, make less than $30,000 annually, or do not own a car.
A Systematic Review on Conditions Before and After Training of Teamwork Competencies and the Effect on Transfer of Skills to the Clinical Workplace
Authors: Wittig Johannes , Krogh Kristian , Blanchard Erin E. , Xing Kuan , Kushner Jodi , Bichmann Anna , Flin Rhona , Brazil Victoria , Goldhaber-Fiebert Sara N. , Paige John , Lauridsen Kasper G. 
Published: August 2024

Summary statement
We conducted a systematic review to assess if any condition before- or after simulation-based training of teamwork competencies for healthcare professionals affects learning or transfer of skills to the clinical environment.
We searched CINAHL, Medline, and Embase for studies published between January 1, 2011, and July 10, 2023. We screened 13,149 abstracts and 335 full texts, of which 5 studies were included. We included primary studies with and without a comparator published in English. We assessed risk of bias using the ROBINS-I tool before narrative synthesis. All studies were observational and reported heterogeneous conditions such as posters, coaching, and leadership support initiatives. Very low certainty evidence suggested that implementing conditions in the clinical environment such as coaching, wider communication of learning objectives, or leadership initiatives could be considered to facilitate the transfer of skill to the clinical environment. Funding: Society for Simulation in Healthcare. Prospero registration: CRD42022320721.
Systematic review and meta-analysis to estimate the burden of non-fatal and fatal overdose among people who inject drugs living in the U.S. and comparator countries: 2010 – 2023
Authors: Shealey Jalissa Y. , Hall Eric W. , Pigott Therese D. , Rosmarin Lexi , Carter Anastasia , Cade Chiquita , Luisi Nicole , Bradley Heather 
Published: August 2024

AbstractBackgroundPeople who inject drugs (PWID) have high risk for overdose, but there are no current estimates of overdose rates in this population. We estimated the rates of non-fatal and fatal overdose among PWID living in the U.S. and comparator countries (Canada, Mexico, United Kingdom, Australia), and ratios of non-fatal to fatal overdose, using literature published 01/01/2010 – 09/29/2023.MethodsPubMed, PsychInfo, Embase, and ProQuest databases were systematically searched to identify publications reporting prevalence or rates of recent (past 12 months) non- fatal and fatal overdose among PWID. Non-fatal and fatal overdose rates were meta-analyzed using random effects models. Risk of bias was assessed using an adapted quality assessment tool, and heterogeneity was explored using sensitivity analyses.ResultsOur review included 143 records, with 58 contributing unique data to the meta- analysis. Non-fatal and fatal overdose rates among PWID in the U.S. were 32.9 per 100 person- years (PY) (95% CI: 26.4 – 40.9; n=28) and 1.7 per 100 PY (95% CI: 0.9 – 3.2; n=4), respectively. Limiting the analysis to data collected after 2016 yielded a non-fatal rate of 41.0 per 100 PY (95% CI: 32.1 – 52.5; n=16) and a fatal rate of 2.5 per 100 PY (95% CI: 1.4 – 4.3; n=2) in the U.S. An estimated 5% of overdoses among PWID in the U.S. result in death. Among the analyzed countries, Australia had the lowest non-fatal and fatal overdose rates and the largest ratio of non-fatal to fatal overdose.ConclusionFindings demonstrate substantial burden of non-fatal and fatal overdose among PWID in the U.S. and comparator countries. Scale-up of interventions that prevent overdose mortality and investments in PWID health research are urgently needed.
Reduced response to SARS-CoV-2 vaccination is associated with impaired immunoglobulin class switch recombination in SLE patients
Authors: Montamat Guillem , Meehan Claire E. , Bradford Hannah F. , Yıldırım Reşit , Guimarães Francisca , Johnson Marina , Goldblatt David , Isenberg David A. , Mauri Claudia 
Published: August 2024

ABSTRACTObjectiveSystemic Lupus Erythematosus (SLE) patients exhibit B-cell abnormalities. Although there are concerns about reduced antibody responses to SARS-CoV-2 vaccines, detailed data on B-cell-specific responses in SLE remain scarce. Understanding the responsiveness to novel vaccine-antigens, and boosters number, is important to avoid unnecessary prolonged isolation of immunocompromised individuals. We assessed humoral and antigen-specific B-cell subset responses, including changes in isotype switching, prior to and after several doses of SARS-CoV-2 vaccines.MethodsBlood samples were obtained prior to and after SARS-CoV-2 vaccination from cross-sectional and longitudinal cohorts of previously uninfected patients with SLE (n=93). Healthy participants receiving SARS-CoV-2 vaccines were recruited as controls (n=135). We measured serum antibody titres, their neutralizing capacity, and vaccine-specific memory B cells subsets.ResultsImpaired IgG, IgA, and neutralizing responses against the original and various SARS-CoV-2 variants were observed following two doses of vaccine in SLE patients. Follow-up booster doses increased humoral responses compared to baseline, but they remained lower, with poorer neutralisation capacity against most strains, compared to healthy individuals after three or more doses. Analysis of memory B-cells subsets in SLE patients revealed an increase of SARS-CoV-2-specific isotype unswitched IgM+over SARS-CoV-2-specific isotype switched IgG+/IgA+memory B-cells compared to healthy individuals. Culturing healthy naive B-cells with high levels of IFNα, a hallmark of SLE pathogenesis, prevented B-cells from switching to IgG under IgG-polarizing conditions.ConclusionSLE patients’ protection against SARS-CoV-2 is overall impaired compared to healthy individuals and is associated with a class switch defect possibly due to chronic exposure of B-cells to IFNα.GRAPHICAL ABSTRACT
Reduced Expression of MTSS1 Increases Sarcomere Number and Improves Contractility in Select Forms of Monogenic DCM
Authors: Kleppe Hannah , Budan Anastasia , Zhang Luke , Majetic Marie , Shenwai Reva , Levinson Alan , Cisne-Thompson Olga , Farshidfar Farshad , Tsui Jonathan , Figarska Sylwia , Hoey Tim , Priest James , Slater Rebecca 
Published: August 2024

ABSTRACTBackgroundThe I-bar protein MTSS1 is a known modifier of heart failure and contractile phenotypes but its role in modulating contractile dysfunction in genetic forms of Mendelian dilated cardiomyopathy (DCM) is not known.MethodsThe potential role of cardiac MTSS1 in TTN DCM was explored using time-to-event models in longitudinal human datasets. Using induced siRNA and mutant forms of pluripotent stem cell cardiomyocytes (iPSC-CMs) the impact of siRNA knockdown of MTSS upon sarcomere and Cardiomyocyte biology was assessed via quantitative high-content microscopy, and the impact and mechanism of MTSS1 knockdown upon contractility was assessed using engineered heart tissues (EHTs).ResultsAmongst individuals affected with TTN DCM, a variant conferring lower cardiac levels of MTSS1 was associated with significantly improved event-free survival from cardiovascular death or heart transplant (HR 0.29, p=0.0016). Knockdown of MTSS1 by siRNA significantly improved the appearance of iPSC-CM models of TTN (p=2.9e-06), CSRP3 (p=3.1e-14), and RBM20 (p=4.4e-04) DCM as assessed by quantitative microscopy. Correspondingly, siRNA knockdown of MTSS1 increased contractility in EHT models of TTN DCM (p=0.003), CSRP3 DCM (p=0.008), and RBM20 DCM (p<2e-16). Across all genetic backgrounds, knockdown of MTSS1 was observed to increase the number of sarcomeres (p<0.0001), and in co-immunoprecipitation experiments MTSS1 physically interacts with MYO18A a key determinant of early sarcomere formation. Knockdown of MTSS1 resulted in increased transcription of MYH7 (0.29 log2FC, p=2.9e-06) along with other sarcomere genes.ConclusionsIn iPSC-CMs Knockdown of MTSS1 by siRNA increased number of sarcomeres and was observed to increase twitch force in select in vitro models, and may suggest MTSS1 plays a previously unrecognized role in modulating sarcomere production. Human observational and iPSC-CM experimental data supports the hypothesis that reduced expression of MTSS1 may be beneficial in Mendelian DCM caused by TTN, RBM20, and CSRP3.
Investigating chromosomal radiosensitivity in inborn errors of immunity: insights from DNA repair disorders and beyond
Authors: Beyls Elien , Duthoo Evi , Backers Lynn , Claes Karlien ,   RAPID clinicians, De Bruyne Marieke , Pottie Lore , Bordon Victoria , Bonroy Carolien , Tavernier Simon J , Claes Kathleen BM , Vral Anne , Baeyens Ans , Haerynck Filomeen 
Published: August 2024

ABSTRACTHuman inborn errors of immunity (IEI) represent a diverse group of genetic disorders affecting the innate and/or adaptive immune system. Some IEI entities comprise defects in DNA repair factors, resulting in (severe) combined immunodeficiencies, bone marrow failure, predisposition to malignancies, and potentially result in radiosensitivity (RS). While other IEI subcategories such as common variable immunodeficiency (CVID) and immune dysregulation disorders also associate with lymphoproliferative and malignant complications, the occurrence of RS phenotypes in the broader IEI population is not well characterized. Nonetheless, identifying RS in IEI patients through functional testing is crucial to reconsider radiation-related therapeutic protocols and to improve overall patient management. This study aimed to investigate chromosomal RS in a diverse cohort of 107 IEI patients using the G0 cytokinesis-block micronucleus (MN) assay. Our findings indicate significant variability in RS across specific genetic and phenotypical subgroups. Severe RS was detected in all ataxia-telangiectasia (AT) patients, a FANCI deficient and ERCC6L2 deficient patient, but not in any other IEI patient included in this cohort. Age emerged as the single influencing factor for both spontaneous and radiation-induced MN yields, while the manifestation of additional clinical features, including infection susceptibility, immune dysregulation, or malignancies did not associate with increased MN levels. Our extensive analysis of RS in the IEI population underscores the clinical importance of RS assessment in AT patients and supports RS testing in all IEI patients suspected of having a DNA repair disorder associated with radiosensitivity.
What do the Welsh public understand about NHS dental services, what do they think they could look like, and what are their priorities? A qualitative study
Authors: Joseph-Williams Natalie , Sha’aban Abubakar , Mazzaschi Francesca , Cope Anthony 
Published: August 2024

AbstractNHS General Dental Services in Wales are undergoing reform. To ensure dental services meet the needs of those who use them, we explored what the public think these services could look like and what their priorities for are.The aim of this study was to consult with the Welsh public to understand their views on NHS dental services to help inform dental reform plans in Wales. Specific objectives were to explore:What do the public think Welsh NHS dental services could look like?What do the public understand about dental services and the dental team?What are their views on skill mix in dentistry?What are their attitudes towards and needs for oral health self-management?What are their priorities for dental care services in Wales?We used qualitative methods (interviews and focus group style workshops) across two phases between November 2023 and May 2024 to explore the study objectives. Thematic analyses were performed on the data to identify key themes. Forty four participants with diverse backgrounds from all seven local health boards in Wales took part.
Extracting and calibrating population evidence of variant pathogenicity using biobank data
Authors: Bhat Vineel , Yu Tian , Brown Lara , Pejaver Vikas , Lebo Matthew , Harrison Steven , Cassa Christopher A. 
Published: August 2024

SummaryAdvancing genomic medicine relies on our ability to assess the phenotypic impacts of rare germline variants, which remains challenging even in highly sequenced monogenic disease genes. Here, we evaluate the use of population sequencing data from the UK Biobank to identify variants which alter disease risk, focusing on familial hypercholesterolemia (FH), hereditary breast and ovarian cancer syndrome (HBOC), and Lynch syndrome (CRC). We model evidence of pathogenicity from population data at the variant level, and demonstrate that odds ratios generated from population cohort data can significantly separate ClinVar pathogenic and benign variants in FH genes (p = 4.5x10-19), HBOC genes (p = 2.5x10-39), and CRC genes (p = 7.6x10-16). Next, to make use of this information in variant assessment, we calibrate population-based odds ratios (ACMG/AMP PS4) at the gene level, and find that they reach ‘strong’ or ‘very strong’ evidence of pathogenicity in 8 of 11 genes, as well as in aggregate. Among participants with a rare variant in these 8 genes, 4.3% (N = 2,456) have a Variant of Uncertain Significance (VUS) or variant not yet observed in ClinVar with strong population evidence of pathogenicity that could inform variant interpretation for a related disorder. In three genes with functional assays, we combine this population evidence with computational, contextual, and experimental evidence. Notably, 12.4% ofLDLRVUS seen in participants have sufficient evidence to be classified as pathogenic. This method offers a scalable approach to integrate evidence of pathogenicity from population data.HighlightsUses population data to identify rare coding variants which increase risk of clinically actionable phenotypes.Population-based disease odds ratios accurately distinguish ClinVar pathogenic and benign variants.Calibrates odds ratios at the gene level to identify their strength of evidence for variant classification.Combines various evidence types to reclassify a substantial fraction of variants of uncertain significance.
Determining Cost-Saving Risk Thresholds for Statin Use
Authors: Gandjour Afschin 
Published: August 2024

AbstractBackgroundStatins are widely prescribed to reduce cholesterol levels and decrease the risk of cardiovascular diseases. This study aims to determine cost-saving risk thresholds for statin use in Germany to inform better prescription practices and healthcare policies.MethodsA decision-analytic approach was employed, using secondary data to compare statin use with no statin use from the perspective of German sickness fund insurees. The analysis focused on cost savings from avoided cardiovascular (CV) events, translating these avoided events into net savings after accounting for treatment costs and potential side effects. The study considered the German adult population insured by sickness funds and used a lifetime horizon for the analysis.ResultsThe maximum number needed to treat (NNT) to achieve cost savings over 10 years was found to be 40, leading to a minimum risk threshold for savings of 9.8%. It was estimated that approximately 22% of the adult population in Germany has a 10-year CV risk of ≥9.8%, potentially avoiding between 307,049 and 705,537 CV events over 10 years, with net population savings of approximately €18 billion.ConclusionsThe current official threshold for statin prescription in Germany, set at a 20% 10-year risk, is too stringent. Lowering the threshold to 9.8% could significantly increase the number of patients benefiting from statin therapy, reducing CV events and generating substantial cost savings. These findings suggest that adjustments to prescription guidelines could improve cardiovascular outcomes and economic efficiency within the German healthcare system.
Movement-responsive deep brain stimulation for Parkinson’s Disease using a remotely optimized neural decoder
Authors: Dixon Tanner C. , Strandquist Gabrielle , Zeng Alicia , Fraczek Tomek , Bechtold Raphael , Lawrence Daryl , Ravi Shravanan , Starr Philip A. , Gallant Jack L. , Herron Jeffrey A. , Little Simon J. 
Published: August 2024

ABSTRACTDeep brain stimulation (DBS) has garnered widespread use as an effective treatment for advanced Parkinson’s Disease (PD). Conventional DBS (cDBS) provides electrical stimulation to the basal ganglia at fixed amplitude and frequency, yet patients’ therapeutic needs are often dynamic with residual symptom fluctuations or side-effects. Adaptive DBS (aDBS) is an emerging technology that modulates stimulation with respect to real-time clinical, physiological, or behavioral states, enabling therapy to dynamically align with patient-specific symptoms. Here, we report a novel aDBS algorithm intended to mitigate movement slowness by delivering targeted stimulation increases during movement using decoded motor signals from the brain. Compared to cDBS and a control algorithm that decreases stimulation during movement, our approach demonstrates enhanced clinical efficacy, with improvements in movement speed, reduced dyskinesia, and better patient-reported therapeutic quality. Furthermore, we demonstrate proof-of-principle of a machine learning pipeline capable of remotely optimizing aDBS parameters in a home setting. This work illustrates the potential of movement-responsive aDBS as a new therapeutic approach and highlights how machine learning assisted programming can simplify optimization to facilitate translational scalability.