bluuebunny/crossref_metadata_2025 huggingface dataset:
“Double Trouble” – the impact of iron infusion and antiresorptive therapy on calcium-phosphate homeostasis
Authors: Stokes Gabrielle , Sheu Angela , Girgis Christian M , White Christopher P
Published: January 2025

Intravenous iron infusions (particularly ferric carboxymaltose) are associated with hypophosphataemia. This is mediated by increased fibroblast growth factor 23 (FGF-23), resulting in decreased activation of 25(OH)vitamin D to 1,25(OH)2 vitamin D and increased urinary phosphate excretion. Similarly, parenteral antiresorptive agents can lead to hypocalcaemia due to reduced bone calcium mobilisation, increasing parathyroid hormone (PTH) secretion and exacerbating kidney phosphate excretion 3. When given concurrently, electrolyte disturbances can be severe and refractory to treatment, necessitating intravenous replacement, frequent monitoring, and prolonged hospitalisation.

We describe a case series of six patients, with severe hypophosphataemia and hypocalcaemia from concurrent administration of intravenous iron and antiresorptive therapy. The average time to hypophosphataemia following iron therapy in the presence of antiresorptives was 17.5 days. This is consistent with the nadir of phosphate two weeks following iron infusion and appears to be prolonged and exacerbated by antiresorptive therapy, increasing urinary phosphate loss through increased PTH activity.

With increasing popularity of intravenous iron infusions and parenteral antiresorptive agents, the interplay of these medications is an important consideration for clinicians. The emerging administration of these agents in the community and fragmentation of care across primary and specialist networks creates the risk of unintentional concurrent use. Increased awareness of their impact on calcium-phosphate homeostasis is needed to mitigate the risk of severe electrolyte derangements with consideration of alternate iron formulations preferentially in those receiving medications for osteoporosis.
Dental manifestations of hypophosphatasia: translational and clinical advances
Authors: Lira dos Santos Elis J , Mohamed Fatma F , Kramer Kaitrin , Foster Brian L
Published: January 2025

Hypophosphatasia (HPP) is an inherited error in metabolism resulting from loss-of-function variants in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNAP). TNAP plays a crucial role in biomineralization of bones and teeth, in part by reducing levels of inorganic pyrophosphate (PPi), an inhibitor of biomineralization. HPP onset in childhood contributes to rickets, including growth plate defects and impaired growth. In adulthood, osteomalacia from HPP contributes to increased fracture risk. HPP also affects oral health. The dentoalveolar complex, that is, the tooth and supporting connective tissues of the surrounding periodontia, include 4 unique hard tissues: enamel, dentin, cementum, and alveolar bone, and all can be affected by HPP. Premature tooth loss of fully rooted teeth is pathognomonic for HPP. Patients with HPP often have complex oral health issues that require multidisciplinary dental care, potentially involving general or pediatric dentists, periodontists, prosthodontists, and orthodontists. The scientific literature to date has relatively few reports on dental care of individuals with HPP. Animal models to study HPP included global Alpl knockout mice, Alpl mutation knock-in mice, and mice with tissue-specific conditional Alpl ablation, allowing for new studies on pathological mechanisms and treatment effects in dental and skeletal tissues. Enzyme replacement therapy (ERT) in the form of injected, recombinant mineralized tissue-targeted TNAP has been available for nearly a decade and changed the prognosis for those with HPP. However, effects of ERT on dental tissues remain poorly defined and limitations of the current ERT have prompted exploration of gene therapy approaches to treat HPP. Preclinical gene therapy studies are promising and may contribute to improved oral health in HPP.
A Theoretical Framework for Transformative Corporate Intergenerational Equity
Authors: Cheong Ben Chester
Published: January 2025

This article argues for the integration of intergenerational equity principles into UK company law to address the growing environmental challenges of the future. Drawing on these principles, it develops a theoretical framework for reconceptualising the corporate form under UK law. The article explores the justifications for this approach, including the need to promote long-term corporate success and address intergenerational equity concerns. It lays the groundwork for future research on operationalising this framework within the UK legal context. Ultimately, the article contends that the integration of intergenerational equity principles into UK company law is not only desirable but also feasible. As such, it contributes to the ongoing debate on corporate purpose, offering a fresh perspective on the role of UK company law in achieving fairness for future generations.
Adaptive analysis on in-situ accelerometer calibration in strong-motion observation network in China
Authors: Ding Lisha , Wu Huadeng , Huang Hui , Lu Zijin , Lao Qian , Yan Xing , Ye Shishan , Chen Jiantao , Zhang Xin
Published: January 2025

The sampling filters used in the National Strong-Motion Observation Network System (NSMONS) of China are linear-phase filters for both real-time transmitted data and locally stored raw data. The performance evaluation of accelerometer is based on human visual assessment through their step calibration response. However, a new re-sampling requirement has been added for the real-time transmitted data of the Earthquake Early Warning System (EEWS) in China, which has a large number of stations. This involves utilizing minimum-phase filters. There are significant challenges in the performance evaluation of accelerometers and the verification of parameter consistency for different data sets within the EEWS in China. Therefore, we propose a method that integrates waveform adaptive identification and analysis of the dynamic characteristics of the accelerometer's step response in the time domain to calculate the overshoot ratio and its changes over time. Our findings indicate that the overshoot ratios of accelerometers, decimated from linear-phase filters and minimum-phase filters, are approximately 7%–9% and 21%–23% respectively under normal sensor operation. Additionally, we reveal the effects of humidity and instrument aging on changes in the transform function of a Force-Balanced Accelerometer (FBA). In practical applications at NSMONS and EEWS in China, the proposed method can automatically identify the starting point of step calibration and detect parameter setting errors and faulty stations. This method has significant generalization potential.
An ACO-LSSVM-Based Identification Method of Fracture-Vug Fillings
Authors: Xu Hao , Lai Fuqiang , Li Jiao , Zeng Chengxiang , Liu Yuejiao , Zeng Yu
Published: January 2025

The types of fracture-vug fillings in carbonate reservoirs play a key role in the storage and transportation of hydrocarbons. Accurate identification of fracture-vug fillings is crucial for evaluating reservoir quality. For the deep carbonate reservoirs of Cambrian Longwangmiao Formation in Muxi Block, we summarized the response characteristics of fillings from coring data, conventional logging data, and electric imaging logging data, and proposed an ant colony algorithm (ACO)-based optimization method of the important parameters of the least-squares support vector machine (LSSVM) for the fracture-vug fillings identification (ACO-LSSVM). Then, based on the refined core descriptions, ACO-LSSVM was applied and validated. The validation results showed that the fracture-vug fillings could be mainly classified as mud fillings, quartz fillings, and carbonate mineral fillings. In addition, reconstructed natural gamma relative value, sonic ratio, density ratio, and other combination curves gave the more obvious responses to different types of fracture-vug fillings than conventional logging curves. Compared to traditional support vector machines (SVM) and random forest (RF) methods, the ACO-LSSVM identification method demonstrates superior performance, with an overall accuracy improvement of more than 10% over the random forest method. Additionally, it exhibits better robustness and a positive feedback mechanism, allowing it to find the optimal solution in a shorter time. The accurate identification of fracture-vug fillings provided the foundation for valid fracture-vug parameter extraction and accurate evaluation of carbonate reservoirs.
Familial adenomatous polyposis family with clustering of psychiatric disorders
Authors: Funaki Masako , Noguchi Atsuko , Ishikawa Hayahito , Noutomi Rie , Fukuda Koji , Shimazu Kazuhiro , Yoshida Taichi , Taguchi Daiki , Shinozaki Hanae , Kodama Naoaki , Mishima Kazuo , Nanjo Hiroshi , Takahashi Tsutomu , Shibata Hiroyuki
Published: January 2025

Familial adenomatous polyposis (FAP) is an inherited disorder that follows an autosomal dominant inheritance pattern and is caused by a germline pathogenic variant in the APC gene. FAP also has extracolonic manifestations, including osteomas, brain tumors, and congenital hypertrophy of the retinal pigmented epithelium. Desmoid tumor is a rare soft-tissue tumor often associated with FAP. APC is a WNT signal transduction molecule that is abundantly expressed in the central nervous system. The truncation mutations of the APC gene are responsible for FAP. Further, the C-terminal domains of APC associate with proteins such as EB1 and hDLG, which are involved in central nervous system functions. In recent years, several reports have indicated an association between FAP and mental disorders. We have identified a family with FAP that has a cluster of mental disorders. The female probrand experienced FAP and desmoid tumors in her thirties. She underwent a total colectomy and tumor resection. Her genetic test revealed a pathogenic germline pathogenic variant in the APC gene, c.3183_3187del. Her maternal grandmother and great-grandmother had colorectal polyposis. She has some mental disorders, and her son and daughter both have autism spectrum disorder (ASD). It was reported that her younger sister and her two daughters have intellectual disability and symptoms of ASD. For these situations, we found that mental health care is crucial when providing genetic counseling and medical care, especially to younger patients with FAP and carriers of pathological variants of the APC gene.
Selumetinib for symptomatic, inoperable plexiform neurofibromas in pediatric patients with neurofibromatosis type 1: the first single-center real-world case series in Japan
Authors: Nishida Yoshihiro , Nonobe Norie , Kidokoro Hiroyuki , Kato Taichi , Takeichi Takuya , Ikuta Kunihiro , Urakawa Hiroshi , Sakai Tomohisa , Koike Hiroshi , Fujito Takeo , Imagama Shiro
Published: January 2025

Objective

In Japan, selumetinib is used in pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic inoperable plexiform neurofibroma (PN). However, there have been no real-world reports on Japanese patients. In this study, we reported a single-center, short-term experience with selumetinib after its approval in Japan.

Methods

We prospectively collected data from 11 pediatric NF1 patients with symptomatic, inoperable PN who were initiated on selumetinib between November 2022 and May 2023; the selumetinib was administered by the same physician. Various patient factors, tumors, dose and efficacy of selumetinib, and adverse events (AE) were investigated.

Results

Of 11 patients included, 7 were male, with a mean age of 14 years. The sites of symptomatic main PN included the head and neck, pelvis to lower extremities, and paraspinal lesions in five, three, and three patients, respectively. The median maximum diameter of the main PN was 91 mm, and the median follow-up duration was 19 months. All patients with pain or motor dysfunction experienced symptom improvement after treatment, and the tumors tended to shrink in 7 of the 11 patients (64%). Among the six patients with disfigurements, only one experienced improvement. Of 59 AEs observed, 58 (98%) were grades 1 and 2, and 5 patients (46%) underwent temporary selumetinib withdrawal due to AEs. One patient discontinued the drug (9%) because of rash dermatitis.

Conclusions

Despite the relatively short-term results, no serious AEs were observed, and many patients benefited from selumetinib treatment. In some patients, administration was discontinued or interrupted because of the balance between benefits and AEs, and further data are needed to better understand the general safety and efficacy of selumetinib.
How to write a judgment: creative writing and international adjudication
Authors: Gasbarri Lorenzo
Published: January 2025

This article focuses on the craft of writing as an essential component of judicial practice. After explaining why writing matters and why the legal scholar can rely on creative writing to describe judicial writing, the article focuses on the sentence, the characters, and the plot as the basic units of the text. The law is made of words, and basic rules of composition can reveal its deeper mechanisms. Whether to include an adverb to highlight the importance, to hide the subject of a sentence to construct an objective truth, or to order the arguments in a favourable structure, writers’ choices reflect the balance of the counteracting interests represented in the judicial proceeding. The article relies both on the close reading of several judgments of international courts and the distant reading of the corpus of decisions of the International Court of Justice, analysed through computational analysis.
Thoracic approach for suspected internal mammary lymph node recurrence following mastectomy and implant-based reconstruction: a case report
Authors: Murayama Daisuke , Hirano Ryosuke , Mishima Osamu , Hashizume Toko
Published: January 2025

The use of video-assisted thoracic surgery (VATS) has increased in recent years. We herein report a case wherein suspected intramammary lymph node (IM) recurrence of breast cancer was treated using the thoracic approach (VATS). A 53-year-old woman had undergone right total mastectomy, axillary lymph node dissection, and implant-based reconstruction for right breast cancer 19 years ago. Hormone therapy was commenced postoperatively. Positron emission tomography as health check up performed at another hospital 1 year prior to presentation revealed enlargement of the right IMs, suggesting recurrence of breast cancer. IM biopsy was performed using VATS to preserve the artificial breast implant. The operative time and blood loss were 157 min and 20 ml, respectively. The postoperative course was favourable. IM biopsy revealed reactive enlargement owing to inflammation. In conclusion, VATS is a safer approach that yields superior outcomes in terms of appearance care.
Innovative microphone transmitter reveals differences in acoustic structure between broadcast and whisper songs of Myadestes obscurus (ʻŌmaʻo)
Authors: Navine Amanda K , Paxton Kristina L , Netoskie Erin C , Tysall Eirlys , Paxton Eben H , Hart Patrick J
Published: January 2025

Low-amplitude “whisper songs” are a taxonomically broad phenomenon in birds that could play an important role in the suite of behaviors birds use to communicate. Due to its cryptic nature, there are inherent difficulties in capturing high-quality whisper song recordings without interrupting natural behaviors. Thus, the whisper song acoustic structure is poorly understood and its potential function remains the subject of debate. Here, we present one of the first quantitative assessments of the acoustic structure of whisper song in birds. Using an innovative microphone transmitter, we collected high-quality recordings of broadcast and whisper songs from the Myadestes obscurus (ʻŌmaʻo), a thrush species endemic to the Island of Hawai’i. The transmitter was attached to the birds and broadcasted radio signals of all vocalizations produced by the individual to distances over 100 m away that minimized disruption of the birds’ normal behavior while recording. We demonstrate that M. obscurus whisper songs are a distinct class of vocalization that differs from broadcast songs in acoustic characteristics beyond amplitude, such as song length, frequency, and length of silent intervals between notes. These findings, in conjunction with habitat-associated variation in the rate at which M. obscurus emit these vocalization classes, indicate broadcast and whisper songs likely serve separate functions. This work provides evidence supporting the acoustic adaptation hypothesis that posits that densely vegetated habitats promote the evolution of songs with specific acoustic features that maintain signal integrity as the sound propagates through the environment.
Pluralism and Partnerships
Authors: Crasnow Sharon , Goertz Gary , Haggard Stephan
Published: January 2025

What justifies multimethod research? This chapter draws on recent debates in the philosophy of science on evidential pluralism and places them in dialogue with the evolution of multimethod research in the social sciences. We pay particular attention to the Russo–Williamson hypothesis, which draws on research in the medical and biological sciences to argue that causation typically involves evidence of both association and mechanisms. The chapter demonstrates how this approach has resonance in the social sciences, but also argues that this is but one form that evidential partnerships might take. It shows this by reviewing a new multimethod approach called Large-N Qualitative Analysis, which draws on regularity approaches to causation to make the point and concludes by suggesting a variety of other evidential partnerships that are visible or might be possible.
Repeated evolution: the case of columellar folds in gastropods
Authors: Vermeij Geerat J
Published: January 2025

Most adaptive traits evolved multiple times independently, but the conditions of their evolution remain obscure. Here I examine the origins of columellar folds, spiral ridges on the axial wall of the interior of many gastropod shells, in both extant and fossil gastropods. Analyses indicate that these features arose at least 46 times, primarily in caenogastropods and heterobranchs. Columellar folds do not form in shells in which the coiling axis rises steeply above the apertural plane and in which the rim of the rounded aperture is a logarithmic spiral. More derived clades have shells with a low angle of elevation of the coiling axis, which permits the evolution of a non-circular aperture, a longer columella, and the formation of columellar folds. This architectural predisposition to form folds long preceded the realization of this potential. Functions of columellar folds include reducing apertural access to predators and preventing anteroposterior displacement of soft parts in the shell as parts of the body slide into and out of the shell. These benefits became important late in gastropod history as metabolic rates and activity levels of gastropods and the threat of predation by way of the aperture increased in the later Mesozoic and Cenozoic eras.
Complications and Cost in Open Versus Endoscopic Lumbar Decompression
Authors: Boden Lauren M. , Boden Susanne H. , Muhammad Najib , Kanzler Matthew A. , Casper David S.
Published: January 2025

Study Design:

A retrospective database study.

Objective:

To compare complications and costs associated with endoscopic and open lumbar decompression on a large scale.

Background:

Though open lumbar decompression is considered the gold standard, endoscopic procedures are on the rise. The majority of studies comparing endoscopic to open decompression have been limited to small retrospective studies or studies in other countries.

Methods:

Patients who underwent single-level endoscopic or open lumbar decompression from 2017 to 2021 with a 2-year follow-up were identified in the PearlDiver database using Current Procedural Terminology and International Classification of Diseases, Tenth Revision codes. Multilevel surgery, concomitant fusion, or cervical/thoracic procedures were excluded. Postoperative complications, including infection, wound dehiscence, and dural tear, were evaluated for both groups, as well as additional lumbar surgery within 2 years. Costs, complications, and rate of repeat surgery were compared between groups.

Results:

A total of 895 endoscopic and 102,258 open lumbar decompression cases met the inclusion criteria. The median age range was 60–64 for both groups, and the majority were low risk on the Charlson Comorbidity Index. Rates of dural tear, infection, and dehiscence were similar between groups. Total cost at 2 years was slightly higher for the endoscopic group ($20,347 vs $18,089, P = 0.03). Patients who underwent endoscopic lumbar decompression were more than twice as likely to undergo a second lumbar surgery in the following 2 years (16% vs 7%, P < 0.00001). Of the patients who underwent additional surgery, there was a higher proportion of patients undergoing reexploration in the open group (33.4% vs 13.8%, P < 0.00001) and a higher proportion undergoing endoscopic decompression in the endoscopic group (35.5% vs 0.64%, P < 0.00001).

Conclusions:

Cost and complication profiles are similar between endoscopic and open lumbar decompression. However, endoscopic decompression patients are more than twice as likely to undergo a second procedure within 2 years. Prospective studies are needed to determine the cause of additional surgery.
Borderline Personality Disorder and Loneliness: Broadening the Scope of Treatment for Social Rehabilitation
Authors: Mermin Sam A. , Steigerwald Georgia , Choi-Kain Lois W.
Published: January 2025

Borderline personality disorder (BPD) has been described as a condition of intolerance of aloneness. This characteristic drives distinguishing criteria, such as frantic efforts to avoid abandonment. Both BPD and loneliness are linked with elevated mortality risk and multiple negative health outcomes. Psychodynamic theories of BPD emphasize fundamental impairment in attachment and interpersonal functioning. Empirical research demonstrates an association between BPD diagnosis and increased loneliness. Individuals with BPD experience higher levels of loneliness than the general population, and their social networks are systematically smaller, less diverse, and less satisfying. Differences in the subjective experience of loneliness persist when controlling for these relevant social network features, indicating that people with BPD experience more loneliness than others in the same objective social circumstances. According to patients with BPD, increased social connection is often a primary treatment goal and marker of satisfying recovery. There are, however, few evidence-based approaches that primarily target loneliness and building life structures that support durable connections with others. Therefore, loneliness persists as an intractable problem, often failing to remit alongside other symptoms, and few resources are routinely implemented to address this problem. In this article, we argue that loneliness is central to the symptomatic oscillations and subjective experiences of many patients with BPD. We propose that treatment extend beyond the overemphasized therapeutic alliance relationship to also promote socialization and group and vocational settings to enhance patients’ social networks. Building larger social networks that rely less on exclusive caregiving and/or romantic relationships and more on role-bound identity building and community relationships would more directly target long-term identity diffusion and relational instability. Such interventions can harness nonclinical community resources, such as group treatment, vocational supports, and peer supports.
Artificial Oxygen Carriers Save Lives in Expanded Access Use: Three Cases when Blood Was Not an Option
Authors: Mei Zhen W. , Raval Jay S. , Arnall Justin , Hwang Sophia H. , Rodberg Karen , Quon Doris , Ward Dawn C. , Ziman Alyssa , McGonigle Andrea M. , Jahr Jonathan S.
Published: January 2025

Clinical features:

Sickle cell patients may develop a multitude of antibodies and experience life-threatening events with transfusion such as hyperhemolysis syndrome or delayed hemolytic transfusion reaction. Further transfusion may not be possible in such cases.

Therapeutic Challenge:

When conventional blood products are not available for transfusion yet the patient requires additional oxygen-carrying support, artificial oxygen carriers may be required. However, there are no such FDA-approved products available.

Solution:

Emergency investigational new drug applications for a polymerized hemoglobin-based oxygen carrier (HBOC-201, Hemopure) were completed, and Expanded Access use was granted for these patients. HBOC-201 is an investigational bovine hemoglobin-based oxygen carrier. Herein, we report how acute resuscitation with HBOC-201 was potentially life saving while waiting for supportive therapy, erythropoietin, and/or immune modulatory drugs to take effect in all 3 patients.
Impact of transesophageal echocardiogram findings on management of acute ischemic stroke: a retrospective single-institution cohort study
Authors: Eltawansy Sherif , Alshami Abbas , Łajczak Paweł , Dandu Sowmya , Apolito Renato
Published: January 2025

Background:

Physicians use transesophageal echocardiography (TEE) as part of the workup for acute ischemic stroke; however, its importance is controversial. While its clinical utility in this patient population may seem logical, based on current data and guideline recommendations, there is no empirical recommendation for using TEE over transthoracic echocardiogram (TTE). This study aimed to provide an update on the TEE’s impact on the clinical outcomes of patients with acute stroke.

Methods:

We conducted a retrospective single-institution cohort study at a tertiary care hospital from June 2021 to August 2022 for patients admitted with new-onset ischemic stroke with or without hemorrhagic conversion who subsequently had a TEE completed at the same admission or after discharge. The primary outcome was the detection of management changes based on TEE results, while secondary outcomes included positive findings leading to embolic stroke, the feasibility of performing TEE as an inpatient versus outpatient procedure, and the TTE yield compared to TEE.

Results:

A total of 176 patients underwent TEE to investigate the cause of stroke. The mean age of those with positive TEE findings was 65.5 years versus 66 years for those with negative or irrelevant findings. Positive TEE patients were 47.7% female versus 45% in the negative findings group. Both age and sex comparisons did not yield statistically significant differences (P values 0.81 and 0.73, respectively). Patients with positive TEE findings accounted for 66 (37.5%), with the most common cardiac pathology being patent foramen ovale (PFO), followed by aortic atherosclerotic plaque. The transthoracic echocardiography (TTE) yield was much lower than that of TEE.

Conclusion:

In patients with newly diagnosed stroke, TEE provided high diagnostic value and impacted the management of 23.9 % of all patients who underwent the test. These findings support its continued use in diagnostic workups, with a higher diagnostic yield than the transthoracic approach.

Conflict of Interest:

The authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript.
The prevalence of musculoskeletal pain, and the risk factor among the residents; a cross-sectional study
Authors: Tarcha Raghad , Alsamarrai Omar , Hodifa Yara , Btrush Sana , Mohammad Aya , Tarcha Majd , Kudsi Maysoun , Latifeh Yousef
Published: January 2025

Background:

A considerable number of resident doctors experience musculoskeletal pain during their residency years. In this study, we seek to determine the prevalence of musculoskeletal pain, as well as its associated risk factors, among a sample of resident doctors.

Methods:

A cross-sectional study was conducted in the Internal Medicine Department of the Faculty of Medicine, with a total of 200 residents participating in filling in the paper-based questionnaire. Standardized Nordic Questionnaire, a modified version was utilized in our study.

Results:

The questionnaire was completed by 200 residents. They were between the ages of 24 and 29 years old, and females were (73%). (54%) of all of them had at least one musculoskeletal pain site in the previous week, while (86%) had at least one musculoskeletal pain site in the last year. On multivariate analysis, factors associated with musculoskeletal pain in the previous week and last year were a familial history of musculoskeletal pain (p = 0.0029) (p = 0.0002), respectively, and a history of trauma (p ≤ 0.001).

Conclusion:

Musculoskeletal pain had a high prevalence among these residents, especially females, those with a history of trauma, and those with a family history of musculoskeletal disorders. This major health problem should be known to medical institutions, and awareness programs are required, in addition to future multicenter and larger studies.
Development and Content Validity of a Questionnaire on Peripheral Intravenous Catheter Maintenance and Knowledge of Nursing Professionals Regarding Best Practices
Authors: Doll Marie Sylvie , Aprile Daniele Cristina Bosco , Gonçalves Alexia Louisie Pontes , da Silva Bianka Sousa Martins , Kusahara Denise Miyuki , Lopes Camila Takáo
Published: January 2025

The aims of this study were to develop a questionnaire on peripheral intravenous catheter (PIVC) maintenance, evaluate its content validity, and assess factors influencing the level of knowledge of nursing professionals regarding best practices.The study was conducted in 3 stages: (1) development of a questionnaire on PIVC maintenance; (2) content validity assessment by experts with assessment of comprehensiveness, relevance, and clarity; and (3) application of the questionnaire to 1493 nursing professionals. Relationships between personal characteristics and knowledge levels were evaluated. The questionnaire score ranged from 0 to 26. The participants obtained a mean score of 13.7 (SD, 2.4). Factors associated with a higher knowledge level included higher educational level, training on PIVC maintenance upon admission, and employment in an institution with recurrent PIVC maintenance training. Gaps in knowledge included the recommended technique for active disinfection, how catheter stabilization should be performed, recommended technique for flushing and minimizing blood reflux into the catheter, appropriate frequency for assessing the insertion site of the catheter, and signs of catheter complications. A questionnaire for assessing knowledge of best practices in PIVC maintenance was developed and had adequate evidence of content validity. Aspects related to greater education were associated with a higher knowledge level. Knowledge gaps were identified.
Composition of the Public Health Workforce: Distribution, Training, and Tenure
Authors: Balio Casey P. , Leslie Haleigh , Meit Michael B.
Published: January 2025

Objective:

Describe the public health and job experience of the local public health workforce at the agency level and based on the characteristics of the jurisdictions they serve.

Design:

Cross-sectional design of U.S. public health workforce at the agency level using 2019 National Association of County and City Health Officials (NACCHO) Profile and 2021 Public Health Workforce Interests and Needs Survey (PH WINS) data.

Setting:

Local health departments across the United States.

Participants:

The sample comprised 248 Local Health Departments (LHDs).

Main Outcome Measure(s):

The percent of the workforce with formal training in public health, percent of the workforce that identifies as women, percent of the workforce with 6 or more years of experience in public health practice, and percent of the workforce with 6 or more years of experience in their current agency.

Results:

Rural-serving LHDs had a greater staffing proportion of women, less formal public health training, and a smaller proportion of staff with 6 or more years of public health practice experience. Gender identity and formal public health training of the top executive of the LHD are correlated with staffing proportions on these measures.

Conclusions:

The local public health workforce composition varies by geography, agency characteristics, and characteristics of the jurisdiction served. Rurality and characteristics of the top executive of the LHD are correlated with the composition of the public health workforce.
Trends and factors associated with HIV viral load non-suppression among treatment-experienced female sex workers in Kenya: a retrospective cohort study
Authors: Mulinge Martin M. , Kimani Humphrey , Inziani Mary , Bwana Priska , Kibui Nancy K. , Wainaina Joseph , Sitati James , Kimani Joshua , Mwau Matilu
Published: January 2025

Background:

Transactional sexual relations in the absence of condom use is a well-established behaviour that strongly contributes to HIV transmission if the infected person is not virally suppressed. In this study, we determined the trends and factors associated with VLNS among treatment-experienced FSWs in Kenya.

Methods:

This retrospective cohort study used data collected from 7-sex workers outreach clinics between 2015 and 2022. VLNS trends were determined using the Modified Mann-Kendall test, and the effects of covariates on VLNS odds were examined using generalized estimating equations (GEE) with a logit link.

Results:

12,117 viral load tests were performed on samples collected from 1,947 FSWs. The prevalence of VLNS decreased from 25.5% (95%CI 17.6–34.6) in 2016 to 4.3% (95%CI 2.5–6.7) in 2021. The odds of VLNS decreased by 9% per year during the study period in the multivariable GEE analysis adjusted for covariates (regimen, age, and sex worker outreach program (SWOP) clinic), (OR 0.91, 95%CI 0.84–0.98; P = 0.005). Age was a significant factor associated with VLNS, with younger women (18–24 years) having 2.2 times higher odds of VLNS (OR 2.15 95%CI 1.10–4.20; P = 0.025) than those aged >55 years (reference). Subjects on dolutegravir (DTG)-based cART regimen had 64% lower odds of VLNS (OR 0.36, 95%CI 0.25–0.52; P < 0.001) compared to those on PI-based regimen.

Conclusions:

There is a strong evidence of decreasing population level viremia among FSWs during the study period. To maintain the trend, it is necessary to continue supporting SWOP clinics in order to provide HIV treatment services to this key population.
Posttraumatic stress disorder and its associations with antiretroviral therapy among veterans with HIV
Authors: Vyas Kartavya J. , Marconi Vincent C. , Agan Brian K. , Sullivan Patrick S. , Lyles Robert H. , Guest Jodie L.
Published: January 2025

Objectives:

Posttraumatic stress disorder (PTSD) may affect antiretroviral therapy (ART) response and clinical outcomes for veterans with HIV (VWH) receiving care in the Department of Veterans Affairs (VA). Objectives are to estimate the associations between PTSD and ART nonadherence, modifications, and failure; measure effect modification by number of deployments and combat exposure; and examine how these associations vary over time.

Design:

In this prospective cohort study of all VWH on ART who deployed to Iraq and Afghanistan and receive care in the VA (n = 3206), patients entered at ART initiation and were censored in December 2022, totaling 22 261 person-years of follow-up.

Methods:

Marginal structural log-binomial and Poisson models were fitted with a time-dependent exposure, adjusted for time-independent and time-dependent confounding and informative censoring, to estimate the associations between PTSD and ART nonadherence, modifications, and failure. Marginal structural shared frailty models were fitted to examine time-varying associations.

Results:

PTSD increased the risk [adjusted risk ratio, 95% confidence interval (CI)] of ART nonadherence by 6% (1.06 [1.00, 1.13]) and the rate (adjusted incidence rate ratio, 95% CI) of ART modifications by 38% (1.38 [1.19, 1.58]). Multiple deployments amplified the association with ART nonadherence by 14%; combat exposure did not modify any association examined. The association with ART modifications increased during the first decade post-PTSD-diagnosis but subsequently stabilized.

Conclusions:

PTSD increased ART nonadherence and ART modifications. Providers should screen for PTSD so that it can help guide medical decisions and treatment; particular attention should be paid to Veterans with multiple combat deployments.
Isolated Temporomandibular Arthritis as Presentation of Juvenile Idiopathic Arthritis
Authors: Bernardo Luca , Visioli Alessandro , Del Giudice Emanuela , Magenes Vittoria Carlotta , Casini Francesca , Chiaffoni Giovanni , Sandini Martina , Ansuini Valentina , Lubrano Riccardo , Mauro Angela
Published: January 2025

Involvement of the temporomandibular joint (TMJ) in patients with juvenile idiopathic arthritis (JIA) has been increasingly reported, affecting up to 87% of cases. This involvement generally occurs after the diagnosis of JIA has been established; however, in the authors' cases, as in a few others documented in the literature, patients presented with isolated TMJ arthritis as the sole joint involvement. The authors performed a narrative literature review on TMJ involvement in JIA and reported 2 cases that presented with isolated TMJ arthritis as the initial manifestation of JIA. Although isolated TMJ involvement may be rare, it can lead to severe complications, such as complete loss of TMJ function. Thus, clinicians should be aware of this potential presentation to conduct necessary investigations and provide appropriate treatment.
Efficient evacuation — enhanced survival: Insights from Gaza conflict trauma care
Authors: Fogel Itay , Balziano Snir , Tunik Michal , Prat Dan , Barzilay Ran , Greenstein Nehemia
Published: January 2025

BACKGROUND

Combat-related injuries have evolved in urban warfare because of close-contact engagements and high-energy blast injuries, with rapid medical evacuation improving survival rates. This study analyzes injury patterns and outcomes in the Gaza conflict, emphasizing the need to optimize trauma care protocols in modern combat environments, particularly because of the unique proximity of conflict zones to tertiary trauma centers.

METHODS

A retrospective study was conducted at a single center involving 189 patients evacuated by helicopter to a Level I tertiary trauma center. Subgroup analysis based on Injury Severity Scores was performed.

RESULTS

Shrapnel impacts were the leading cause of injuries (58.7%), followed by blast injuries (48.1%) and gunshot wounds (30.7%). Extremity injuries were most common (61.4%), with 46.3% of patients needing surgery within 24 hours, mainly orthopedic procedures (75.3%). The average hospital stay was 21.9 days. In-hospital mortality rate was 4.2% (two patients). Infections occurred in 17.9% of cases, with fungal infections at 8.9% and bacterial infections at 15.3%.

CONCLUSION

In modern urban warfare, effective medical interventions play a crucial role in mitigating challenges. This study emphasizes the importance of rapid evacuation and advanced trauma management, reflected in low in-hospital mortality rates, highlighting the significance of timely interventions, personal protective equipment, specialized orthopedic trauma care, and robust infection control measures.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Detection of butyrate from a Clostridium cluster I (Clostridium sensu stricto) strain, Clostridium tertium, under anaerobic conditions
Authors: Miyazaki Mei , Kaneko Nanako , Hardy Nicholas , Iwai Hiroki
Published: January 2025

Lactic acid bacteria and Bacillus bifidus are well-known probiotics used as alternatives to conventional pharmacotherapy in infectious diseases. Butyric acid (butyrate) bacteria such as Clostridium butyricum are also useful probiotics but have been rarely studied. To identify new butyrate-producing bacterial species, we examined the production of organic acids, including butyrate, in Clostridium tertium and C. butyricum. Protein BLAST (BLASTP) searches for butyrate kinase (BUK) proteins in the genomes of C. tertium have identified two proteins. To confirm their presence in the genome of C. tertium, we detected two buk genes using polymerase chain reaction (PCR). As phosphotransbutyrylase (ptb), a buk gene adjacent gene, was also present in the announced C. tertium genome, which was confirmed using PCR. Next, we investigated butyrate production in C. tertium. Lactic acid (lactate), formic acid (formate), acetic acid (acetate), and butyrate were detected in both thioglycolate medium cultures. Thus, we concluded that C. tertium produces butyrate. Our findings describe a novel butyrate-producing bacterium as a potential probiotic.
On the Estimation of the Time-Dependent Transmission Rate in Epidemiological Models
Authors: Zubelli Jorge P. , Loria Jennifer , Albani Vinicius V. L.
Published: January 2025

The COVID-19 pandemic highlighted the need to improve the modeling, estimation, and prediction of how infectious diseases spread. SEIR-like models have been particularly successful in providing accurate short-term predictions.

This study fills a notable literature gap by exploring the following question: Is it possible to incorporate a nonparametric susceptible-exposed-infected-removed (SEIR) COVID-19 model into the inverse-problem regularization framework when the transmission coefficient varies over time?

Our positive response considers varying degrees of disease severity, vaccination, and other time-dependent parameters. In addition, we demonstrate the continuity, differentiability, and injectivity of the operator that link the transmission parameter to the observed infection numbers.

By employing Tikhonov-type regularization to the corresponding inverse problem, we establish the existence and stability of regularized solutions. Numerical examples using both synthetic and real data illustrate the model’s estimation accuracy and its ability to fit the data effectively.
Automated Digital Biomarker Discovery Pipeline for Cardiovascular Diseases
Authors: Manimaran Gouthamaan , Puthusserypady Sadasivan , Dominguez Helena , Bardram Jakob E.
Published: January 2025

Cardiovascular Diseases (CVDs) are the leading cause of mortality worldwide, necessitating early and accurate diagnosis to prevent severe outcomes such as Heart Failure (HF). Despite the widespread use of Electrocardiogram (ECG) for cardiac monitoring, traditional methods often miss subtle preclinical changes. In this paper, we present an automated digital biomarker discovery pipeline that leverages explainable artificial intelligence (XAI) to enhance the interpretability and clinical applicability of ECG-based biomarkers for CVDs. Using an inter-pretable feature extractor combined with unsupervised clustering and Particle Swarm Optimisation (PSO), our method identifies both known and novel ECG features associated with high CVD risk. These include established markers like RR Interval Sample Entropy and the discovery of novel biomarkers such as T-Wave Multiscale Entropy, which we found to be significantly associated with CVD risk. Our pipeline enhances early detection by bridging Artificial Intelligence (AI) methods with clinical relevance, providing interpretable insights that align with physiological principles. This transparency promotes clinician trust and supports the integration of AI into routine medical practice. Our results demonstrate that this approach can significantly improve the prediction and understanding of heart diseases, thus offering a powerful tool for reducing the global burden of CVDs.
Cycling Molecular Assemblies for Selective Cancer Cell Golgi Disruption
Authors: Tan Weiyi , Zhang Qiuxin , Liu Zhiyu , Qiu Kangqiang , Mahajan Divyanshu , Gerton Thomas , Copperman Noah , Xia Chaoshuang , Lin Cheng , Lau William , Lee Mikki , Ashton-Rickardt Isabela , Hong Pengyu , Dinulescu Daniela , Hsieh Jer-Tsong , Loeb David , Drapkin Ronny , Diao Jiajie , Lu Lei , Xu Bing
Published: January 2025

The Golgi apparatus is a critical organelle responsible for intracellular trafficking and signaling, orchestrating essential processes such as protein and lipid sorting1–5. Dysregulation of its function has been implicated in various pathologies, including obesity, diabetes, and cancer, highlighting its importance as a potential therapeutic target. Despite this, the development of tools to selectively target the Golgi in specific cell types remain a significant unmet challenge in imaging and drug discovery. Golgi-specific enzyme activities, such as those mediated by protein acyltransferases and thioesterases6, offer an untapped opportunity to develop subcellularly localized therapeutics. Current approaches predominantly rely on direct protein binding but lack the necessary cell selectivity7, underscoring the unmet need for innovative strategies to selectively disrupt Golgi function in cancer cells. Here, we report the development of cycling molecular assemblies (CyMA), a novel class of small peptide derivatives (e.g., dipeptides), which exploit the unique enzymatic environment of the Golgi to establish futile cycles of reversible S-acylation. These assemblies selectively accumulate in cancer cell Golgi, interfering with protein S-acylation cycles and disrupting organelle homeostasis. CyMA impair key Golgi functions, including protein trafficking, glycosylation, and secretion, while demonstrating selective sparing hepatocytes and immune cells such as M1 macrophages. This selective activity represents a paradigm shift, utilizing an enzyme switch and leveraging intracellular environment rather than direct protein binding. Unlike conventional approaches, CyMA reduce tumor growth, drug resistance, and metastasis by pleiotropically disrupting Golgi related functions. By demonstrating the potential of futile cycles as a therapeutic strategy8, this study introduces a generalizable method for targeting organelle-specific enzyme activities. These findings not only underscore the therapeutic potential of CyMA in cancer but also pave the way for future applications in other Golgi-associated diseases.
Electrospinning of hydroxypropyl chitosan nanofibers for bone regeneration application
Authors: Wang Junmei , Xiong Jie , Li Guozhao , Zhou Ziliang , Yang Yanyan , He Lu
Published: January 2025

To study the effect of electrospinning nanofiber mats synthesized using hydroxypropyl chitosan in conjugation with poly (vinyl alcohol) on the osteogenesis in MC3T3 cell, we fabricated different ratios of hydroxypropyl chitosan (HPCH) and poly (vinyl alcohol) to electrospin the nanofiber mats, the mechanical and physical properties of nanofiber mats were tested by using SEM, FT-IR and conventional methods. Then the effect of the electrospinning mats on osteogenesis in MC3T3 cell were evaluated by Alizarin Red stain, ALP stain and expression of relevant genes. We found that the nanofiber mats fabricated by hydroxypropyl chitosan (50%) and poly (vinyl alcohol)(50%) can induce osteoblast differentiation apparently in MC3T3 cell.
Mumemto: efficient maximal matching across pangenomes
Authors: Shivakumar Vikram S. , Langmead Ben
Published: January 2025

Aligning genomes into common coordinates is central to pangenome analysis and construction, but it is also computationally expensive. Multi-sequence maximal unique matches (multi-MUMs) are guideposts for core genome alignments, helping to frame and solve the multiple alignment problem. We introduce Mumemto, a tool that computes multi-MUMs and other match types across large pangenomes. Mumemto allows for visualization of synteny, reveals aberrant assemblies and scaffolds, and highlights pangenome conservation and structural variation. Mumemto computes multi-MUMs across 320 human genome assemblies (960GB) in 25.7 hours with under 800 GB of memory, and over hundreds of fungal genome assemblies in minutes. Mumemto is implemented in C++ and Python and available open-source athttps://github.com/vikshiv/mumemto.