bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of BRCA1 and BRCA2 Germline Variant Data From Patients With Breast Cancer in a Real-World Data Registry
Authors: Nepomuceno Thales C. , Lyra Paulo , Zhu Jianbin , Yi Fanchao , Martin Rachael H. , Lupu Daniel , Peterson Luke , Peres Lauren C. , Berry Anna , Iversen Edwin S. , Couch Fergus J. , Mo Qianxing , Monteiro Alvaro N. 
Published: May 2024

PURPOSE The emergence of large real-world clinical databases and tools to mine electronic medical records has allowed for an unprecedented look at large data sets with clinical and epidemiologic correlates. In clinical cancer genetics, real-world databases allow for the investigation of prevalence and effectiveness of prevention strategies and targeted treatments and for the identification of barriers to better outcomes. However, real-world data sets have inherent biases and problems (eg, selection bias, incomplete data, measurement error) that may hamper adequate analysis and affect statistical power. METHODS Here, we leverage a real-world clinical data set from a large health network for patients with breast cancer tested for variants in BRCA1 and BRCA2 (N = 12,423). We conducted data cleaning and harmonization, cross-referenced with publicly available databases, performed variant reassessment and functional assays, and used functional data to inform a variant's clinical significance applying American College of Medical Geneticists and the Association of Molecular Pathology guidelines. RESULTS In the cohort, White and Black patients were over-represented, whereas non-White Hispanic and Asian patients were under-represented. Incorrect or missing variant designations were the most significant contributor to data loss. While manual curation corrected many incorrect designations, a sizable fraction of patient carriers remained with incorrect or missing variant designations. Despite the large number of patients with clinical significance not reported, original reported clinical significance assessments were accurate. Reassessment of variants in which clinical significance was not reported led to a marked improvement in data quality. CONCLUSION We identify the most common issues with BRCA1 and BRCA2 testing data entry and suggest approaches to minimize data loss and keep interpretation of clinical significance of variants up to date.
Cost-effectiveness of Genetic Testing of Endocrine Tumor Patients Using a Comprehensive Hereditary Cancer Gene Panel
Authors: Patócs Attila , Nagy Petra , Papp János , Bozsik Anikó , Antal Bálint , Grolmusz Vince Kornél , Pócza Tímea , Butz Henriett 
Published: May 2024

Abstract

Introduction
Heterogenous clinical manifestations, overlapping phenotypes, and complex genetic backgrounds are common in patients with endocrine tumors. There are no comprehensive recommendations for genetic testing and counseling of these patients compared to other hereditary cancer syndromes. The application of multigene panel testing is common in clinical genetic laboratories, but their performance for patients with endocrine tumors has not been assessed.

Methods
As a national reference center, we prospectively tested the diagnostic utility and cost-efficiency of a multigene panel covering 113 genes representing genetic susceptibility for solid tumors; 1279 patients (including 96 cases with endocrine tumors) were evaluated between October 2021 and December 2022 who were suspected to have hereditary tumor syndromes.

Results
The analytical performance of the hereditary cancer panel was suitable for diagnostic testing. Clinical diagnosis was confirmed in 24% (23/96); incidental findings in genes not associated with the patient's phenotype were identified in 5% (5/96). A further 7% of pathogenic/likely pathogenic variants were detected in genes with potential genetic susceptibility roles but currently no clear clinical consequence. Cost-benefit analysis showed that the application of a more comprehensive gene panel in a diagnostic laboratory yielded a shorter turnaround time and provided additional genetic results with the same cost and workload.

Discussion
Using comprehensive multigene panel results in faster turnaround time and cost-efficiently identifies genetic alterations in hereditary endocrine tumor syndromes. Incidentally identified variants in patients with poor prognoses may serve as a potential therapeutic target in tumors where therapeutic possibilities are limited.
The Role of Imatinib in Pediatric Type 1 Diabetes
Authors: Lavelle Kristen , Chamberlain Chester , German Michael , Anderson Mark , Nip Angel , Gitelman Stephen E 
Published: May 2024

Abstract
We report the first case of imatinib use in an adolescent with diabetes and suggest that it impacts the natural course of disease. A 14-year-old male patient presented in diabetic ketoacidosis (DKA) and was diagnosed with presumed autoantibody-negative type 1 diabetes (T1D) as well as myeloid neoplasm with platelet-derived growth factor receptor beta (PDGFRB) rearrangement. After starting exogenous insulin and imatinib, he experienced a 1.7-point reduction in glycated hemoglobin (HbA1c) and a 71% reduction in insulin requirement with sustained partial diabetes remission. Our case suggests imatinib as a potential therapeutic agent for pediatric T1D.
THRB Gene Mosaicism Confirmed by Next-Generation Sequencing in a Clinically Symptomatic Infant
Authors: Cheng Jenny Yeuk Ki , Subramaniam Shreenidhi Ranganatha , Leung Hoi Shan , Wong Sammy Wai Chun , Kwok Jeffrey Sung Shing , Lam Wai Kei Jacky 
Published: May 2024

Abstract
A 4-day-old infant was admitted for neonatal jaundice. He had persistent tachycardia and tachypnea. Initial workup showed a serum free T4 of 75.6 pmol/L (5.87 ng/dL) (reference range: 11.5-28.3 pmol/L; 0.89-2.20 ng/dL) and a nonsuppressed TSH 3.76 mIU/L (reference range: 0.72-11.0 mIU/L). A TRH stimulation test showed an exaggerated TSH response with a peak of 92.1 mIU/L at 30 minutes after TRH injection, which suggested the diagnosis of resistance to thyroid hormone β syndrome. Sanger sequencing showed a questionable pathogenic variant in the THRB gene with low signal amplitude. Restriction fragment length polymorphism was consistent with its presence. The variant was originally reported as heterozygous. Next-generation sequencing was performed on blood and buccal swab samples of the patient and his parents, which confirmed this de novo mosaic variant NM_000461.5:c.1352T &gt; C p.(Phe451Ser) in the patient but not in his asymptomatic parents. As it was in a mosaic state, only the offspring, but not other first-degree relatives, of the patient would have the risk of inheriting that variant.
Correlation Between Glycemic Control and Serum Thyroglobulin Levels in a Patient With RAI-Refractory Thyroid Cancer
Authors: Hataya Yuji , Nomura Takumi , Fujishima Yuko , Fujimoto Kanta , Iwakura Toshio , Matsuoka Naoki 
Published: May 2024

Abstract
Diabetes is a risk factor for thyroid cancer development. Serum thyroglobulin (Tg) levels are useful as sensitive and specific tumor markers for monitoring radioiodine (RAI)-refractory thyroid cancer; however, the impact of glycemic control on serum Tg levels is poorly understood. Here, we present a case of a female patient with lung metastases of RAI-refractory thyroid cancer in whom glycemic control may have influenced the serum Tg levels. Despite receiving thyroid-stimulating hormone suppression therapy, her serum Tg levels remained elevated. Subsequently, she developed type 2 diabetes and was administered antidiabetic medications for 6 years. Throughout the course of diabetes management, her serum Tg levels fluctuated according to the level of glycemic control, showing a strong correlation with her hemoglobin A1c levels (r = 0.92, P &lt; .01). Similar to the serum levels of other tumor markers, such as the carcinoembryonic antigen and carbohydrate antigen 19-9, the serum levels of Tg can be influenced by glycemic control. Therefore, serum Tg levels in patients with RAI-refractory thyroid cancer and diabetes should be monitored with attention to glycemic control.
Cubital Tunnel Syndrome Due to Intraneural Ganglion Cysts of the Ulnar Nerve With Joint-Cyst Connection at the Elbow
Authors: Li Hui , Gao Lei , Qi Hengtao , Guan Shibing 
Published: May 2024

BACKGROUND AND OBJECTIVES:
The unifying articular theory suggests that intraneural ganglion cysts in the cubital tunnel arise from the elbow joint and are connected to the ulnar nerve through an articular branch. This study aimed to report our clinical experience with these cysts and our surgical findings and outcomes.

METHODS:
We retrospectively analyzed 13 patients who underwent surgery for cubital tunnel syndrome caused by an intraneural ganglion cyst of the ulnar nerve. Clinical symptoms, physical examination findings, nerve conduction testing electromyography, plain radiography, and ultrasonography were evaluated before and after surgery. MRI was performed in 2 patients. Cyst decompression, disconnection of the articular branch, and ulnar nerve transposition were performed in all.

RESULTS:
The mean follow-up was 29 months. After surgery, local elbow pain and Tinel sign disappeared in all patients, and the average Numerical Rating Scale dropped from 3.7 (2-5) to 0 (0-0). Two-point discrimination testing was normal (<5.0 mm) in 12 patients. Wartenberg sign and “claw hand” deformity became negative, and muscle function and motor nerve conduction velocity were improved in 12 patients. The Medical Research Council muscle strength grade was M4 or M5 in the flexor carpi ulnaris, flexor digitorum profundus of the 4th and 5th digits, and first dorsal interosseous muscle in 12 patients. Postoperative spontaneous potentials including fibrillation and sharp waves, and motor unit recruitment in the first dorsal interosseous muscle were obviously improved. A cystic articular branch was confirmed during surgery in all patients. No cyst recurred clinically or on follow-up ultrasonography.

CONCLUSION:
The unifying articular theory of intraneural ganglion cysts applies to those located in the ulnar nerve at the elbow. Surgical disconnection of the articular nerve branch from the ulnar nerve eliminated the pathway for cyst recurrence and achieved good long-term outcomes.
Safety and Efficacy of Surgical Implantation of Intrathecal Drug Delivery Pumps in Patients With Cancer With Refractory Pain
Authors: Winston Graham M. , Zimering Jeffrey H. , Newman Christopher W. , Reiner Anne S. , Manalil Noel , Kharas Natasha , Gulati Amitabh , Rakesh Neal , Laufer Ilya , Bilsky Mark H. , Barzilai Ori 
Published: May 2024

BACKGROUND AND OBJECTIVES:
Pain management in patients with cancer is a critical issue in oncology palliative care as clinicians aim to enhance quality of life and mitigate suffering. Most patients with cancer experience cancer-related pain, and 30%-40% of patients experience intractable pain despite maximal medical therapy. Intrathecal pain pumps (ITPs) have emerged as an option for achieving pain control in patients with cancer. Owing to the potential benefits of ITPs, we sought to study the long-term outcomes of this form of pain management at a cancer center.

METHODS:
We retrospectively reviewed medical records of all adult patients with cancer who underwent ITP placement at a tertiary comprehensive cancer center between 2013 and 2021. Baseline characteristics, preoperative and postoperative pain control, and postoperative complication rate data were collected.

RESULTS:
A total of 193 patients were included. We found that the average Numerical Rating Scale (NRS) score decreased significantly by 4.08 points (SD = 2.13, P < .01), from an average NRS of 7.38 (SD = 1.64) to an average NRS of 3.27 (SD = 1.66). Of 185 patients with preoperative and follow-up NRS pain scores, all but 9 experienced a decrease in NRS (95.1%). The median overall survival from time of pump placement was 3.62 months (95% CI: 2.73-4.54). A total of 42 adverse events in 33 patients were reported during the study period. The 1-year cumulative incidence of any complication was 15.6% (95% CI: 10.9%-21.1%) and for severe complication was 5.7% (95% CI: 3.0%-9.7%). Eleven patients required reoperation during the study period, with a 1-year cumulative incidence of 4.2% (95% CI: 2.0%-7.7%).

CONCLUSION:
Our study demonstrates that ITP implantation for the treatment of cancer-related pain is a safe and effective method of pain palliation with a low complication rate. Future prospective studies are required to determine the optimal timing of ITP implantation.
Latitudinal variation in thermal performance of the common coral Pocillopora spp.
Authors: Edmunds P. J. , Combosch D. J. , Torrado H. , Sakai K. , Sinniger F. , Burgess S. C. 
Published: May 2024

ABSTRACT
Understanding how tropical corals respond to temperatures is important to evaluating their capacity to persist in a warmer future. We studied the common Pacific coral Pocillopora over 44° of latitude, and used populations at three islands with different thermal regimes to compare their responses to temperature using thermal performance curves (TPCs) for respiration and gross photosynthesis. Corals were sampled in the local autumn from Moorea, Guam and Okinawa, where mean±s.d. annual seawater temperature is 28.0±0.9°C, 28.9±0.7°C and 25.1±3.4°C, respectively. TPCs for respiration were similar among latitudes, the thermal optimum (Topt) was above the local maximum temperature at all three islands, and maximum respiration was lowest at Okinawa. TPCs for gross photosynthesis were wider, implying greater thermal eurytopy, with a higher Topt in Moorea versus Guam and Okinawa. Topt was above the maximum temperature in Moorea, but was similar to daily temperatures over 13% of the year in Okinawa and 53% of the year in Guam. There was greater annual variation in daily temperatures in Okinawa than Guam or Moorea, which translated to large variation in the supply of metabolic energy and photosynthetically fixed carbon at higher latitudes. Despite these trends, the differences in TPCs for Pocillopora spp. were not profoundly different across latitudes, reducing the likelihood that populations of these corals could better match their phenotypes to future more extreme temperatures through migration. Any such response would place a premium on high metabolic plasticity and tolerance of large seasonal variations in energy budgets.
Wavelength-specific negatively phototactic responses of the burrowing mayfly larvae Ephoron virgo
Authors: Mészáros Ádám , Kriska György , Egri Ádám 
Published: May 2024

ABSTRACT
Mayflies are typically negatively phototactic during larval development, whereas the adults possess positive phototaxis. However, no extensive research has been done into the wavelength dependence of phototaxis in any mayfly larvae. We measured the repellency rate of Ephoron virgo larvae to light as a function of wavelength in the 368–743 nm spectral range. We established that the magnitude of repellence increased with decreasing wavelength and the maximal responses were elicited by 400 nm violet light. This wavelength dependence of phototaxis is similar to the recently reported spectral sensitivity of positive phototaxis of the twilight-swarming E. virgo adults. Negative phototaxis not only facilitates predation evasion: avoidance of the blue-violet spectral range could also promote the larvae to withdraw towards the river midline in the case of a drop in the water level, when the underwater light becomes enriched with shorter wavelengths as a result of the decreasing depth of overhead river water.
Learning to Optimize Contextually Constrained Problems for Real-Time Decision Generation
Authors: Babier Aaron , Chan Timothy C. Y. , Diamant Adam , Mahmood Rafid 
Published: May 2024

The topic of learning to solve optimization problems has received interest from both the operations research and machine learning communities. In this paper, we combine ideas from both fields to address the problem of learning to generate decisions to instances of optimization problems with potentially nonlinear or nonconvex constraints where the feasible set varies with contextual features. We propose a novel framework for training a generative model to produce provably optimal decisions by combining interior point methods and adversarial learning, which we further embed within an iterative data generation algorithm. To this end, we first train a classifier to learn feasibility and then train the generative model to produce optimal decisions to an optimization problem using the classifier as a regularizer. We prove that decisions generated by our model satisfy in-sample and out-of-sample optimality guarantees. Furthermore, the learning models are embedded in an active learning loop in which synthetic instances are iteratively added to the training data; this allows us to progressively generate provably tighter optimal decisions. We investigate case studies in portfolio optimization and personalized treatment design, demonstrating that our approach yields advantages over predict-then-optimize and supervised deep learning techniques, respectively. In particular, our framework is more robust to parameter estimation error compared with the predict-then-optimize paradigm and can better adapt to domain shift as compared with supervised learning models. This paper was accepted by Chung Piaw Teo, optimization. Funding: This work was supported in part by the Natural Sciences and Engineering Research Council of Canada. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2020.03565 .
Bouncing your way to labour and birth using biomechanics and fetal optimal positioning
Authors: Lennon Roisin 
Published: May 2024

Background/Aims ‘Labour hopscotch’ is a visual tool that encourages activity during pregnancy and childbirth. It has been used in one advanced midwife practitioner service since 2017 and more widely across in Ireland since 2020. The biomechanics for birth toolkit was added to advanced midwife practitioner care in 2022. This study's aim was to ascertain if the biomechanics for birth toolkit impacted gestation of spontaneous onset of labour rates and birth outcomes. Methods A retrospective study of onset of labour and birth outcomes was conducted for women before (n=155) and after (n=154) the biomechanics for birth toolkit was incorporated into care. Results Before the toolkit was included, there was a 57.2% spontaneous onset of labour rate, with 33.2% birthing before 41 weeks. After the kit's inclusion, there was a 72.2% spontaneous onset of labour, with 91.8% birthing before 41 weeks. Induction rates dropped from 42.8% to 27.8%, with emergency caesarean section rates following induction dropping from 33.1% to 23.8%. Conclusions Using the biomechanics for birth toolkit alongside the labour hopscotch tool could increase spontaneous onset of labour rates, optimise physiological birth, reduce inductions and emergency caesarean section following induction.
Qualitative service evaluation of a rural midwife-led ultrasound service: listening to women
Authors: Jones Lynn 
Published: May 2024

Background/Aims Patient experience is needed to understand if a service is meeting the needs of the population it serves. In rural areas, accessing maternity services can be challenging for women. Local provision should be explored and consistently reviewed to adapt to changing social requirements and expectations. The aim of this study was to examine a rural midwifery-led ultrasound service 5 years after implementation and post COVID-19, to ascertain if the service provides a positive service user experience. Methods A qualitative service evaluation was carried out using semi-structured interviews with four service users. Data were analysed using content analysis. Results Positive aspects of the service included continuity of care, communication, time to care, financial benefits and inclusivity in care and care decisions. It was noted that the ultrasound service was in the opposite direction from their homes to the obstetric service if participants needed to be referred for consultant opinion the same day. The significant underlying theme was the positive impact on mental wellbeing and patient experience in pregnancy when attending the service. Conclusions There was a high level of satisfaction with the service. Engagement of a broader spectrum of women would provide deeper insight into the service and robust evidence for any service development.
Enhancing secret key distribution through advanced color modulation in visible light communication
Authors: Figueiredo Gonçalo , Ferreira Rute A. S. , André Paulo S. 
Published: May 2024

Visible light communication (VLC) has emerged as a dynamic area of research poised to revolutionize high-speed wireless communication. VLC technology uses light-emitting diodes (LEDs) within existing infrastructure to emit light within the visible spectrum. VLC complements traditional radio frequency (RF) communications, addressing its inherent limitations and drawbacks. To navigate the demands of modern urban environments, VLC systems must prioritize secure data transmission, accessibility, and economic feasibility, particularly within the framework of smart cities. We introduce what is to our knowledge a novel privacy-enhanced VLC system for optical wireless communication. Leveraging color data modulation techniques and the intricacies of a hyperchaotic three-dimensional map, this innovative approach ensures robust security. By employing diverse LED colors for data transmission and exploiting the unpredictable mathematical properties of hyperchaotic maps, enhanced privacy is achieved. The performance of the proposed system was rigorously evaluated through various tests, manipulating initial control parameters of the encryption process with the hyperchaotic map, as well as adjusting message length and content. Tests were conducted over a 1 m connection distance at a symbol transmission rate of 2 baud. Remarkably, the proposed system demonstrated high accuracy in message recovery, achieving a symbol error rate (SER) of only 0.02 at an incident optical power of 22 µW. We highlight the critical importance of precise decryption parameter values in the proposed method, demonstrating the necessity for accuracy within the range of 10−15 for each decryption parameter; it underscores the indispensability of meticulous parameter calibration to ensure the correct decryption of transmitted symbols. These results pave the way for applications where absolute security is imperative, particularly in smart city environments, such as for key distribution purposes.
Geteiltes Wissen, gestärkte Resilienz: Informationsaustausch über Cyberbedrohungen gemäß Art. 45 DORA
Authors: Waschbusch Gerd , Schlenker Ben 
Published: May 2024

ZusammenfassungDie zunehmende Bedrohung durch Cyberangriffe stellt insbesondere die Finanzbranche vor große Herausforderungen. Der ab dem 17. Januar 2025 geltende Digital Operational Resilience Act (DORA) verpflichtet Finanzunternehmen in der EU daher zu einem umfassenden Management von IKT-Risiken, um ihre digitale operationale Resilienz zu stärken. Der Austausch von Informationen und Erkenntnissen über Cyberbedrohungen, insbesondere sogenannter Threat Intelligence, spielt eine zentrale Rolle beim Schutz vor Cyberangriffen. Der DORA fördert deshalb den europaweiten Informationsaustausch zwischen Finanzunternehmen durch die erstmalige Schaffung eines einheitlichen gesetzlichen Rahmens. Bisher findet ein solcher Austausch hauptsächlich auf nationaler Ebene statt. Dieser Beitrag beleuchtet den regulatorischen Rahmen für den Austausch von Informationen und Erkenntnissen über Cyberbedrohungen gemäß DORA. Berücksichtigt werden dabei insbesondere Interdependenzen zu dem Recht zum Schutz von Geschäftsgeheimnissen, dem Datenschutzrecht und dem Wettbewerbsrecht. Darüber hinaus werden bestehende Kooperationsformen vorgestellt, wie die Allianz für Cybersicherheit, der Verein Cyber Security Sharing and Analytics, die European Cloud User Coalition und die TIBER-DE Community.