bluuebunny/crossref_metadata_2025 huggingface dataset:
Moving Forward Together: Establishing an Actionable Pedagogical Approach to Ableism-Aware Medical Education
Authors: Tolchin Dorothy W. , Ankam Nethra S. , Bosques Glendaliz , Kasi Ravi , Sauter Carley , Therattil Maya , Rydberg Leslie
Published: December 2024

As a form of discrimination, ableism impacts access to and the experience of clinical care for patients with disabilities as well as the daily experiences of learners and clinicians with disabilities. Ableist beliefs and practices conflict with physicians’ professional responsibilities and legal obligations to provide care that is nondiscriminatory and accessible. An actionable pedagogical approach within medical education is needed to prepare a physician workforce that is able to meaningfully identify and mitigate ableism at all levels of the health care system.

In this article, the authors propose a 3-pronged approach to ableism-aware medical education, building on frameworks that have been articulated for addressing other forms of discrimination to set forth a practical framework easily adopted by educators who may not be experts in ableism and its impact. The 3-pronged approach aligns with American Medical Association and Association of American Medical Colleges perspectives on advancing health equity and is inclusive of priority areas articulated by stakeholders, including those living with disability, those teaching about disability, and those advancing equity within medicine more broadly. The authors provide strategies relevant to medical students, faculty, and institutions, recognizing that ableism exists—and can be addressed—on multiple levels.
Refractory hypoglycemia is sensitive to octreotide therapy: is it triggered by sorafenib or hepatocellular carcinoma?
Authors: Çakmak Mehmet , Bal Öznur , Kiraci Murat , Topaloğlu Oya , Köş Fahriye Tuğba , Algin Efnan
Published: December 2024

Hypoglycemia is a medical emergency with a multitude of potential causes. Paraneoplastic hypoglycemia represents a rare cause of this condition. Hepatocellular carcinoma (HCC) can result in paraneoplastic hypoglycemia through extensive tumor infiltration and the presence of insulin-like growth factor 2 precursors. In this article, a patient whose persistent hypoglycemia did not improve despite long-term intravenous glucose and high-dose steroid treatment and who was successfully treated with octreotide is described. A 50-year-old male patient with a diagnosis of metastatic HCC was admitted to the emergency department due to symptomatic hypoglycemia. His blood glucose level was found to be 40 mg/dl and he was hospitalized in our clinic for treatment. The patient, who had been on sorafenib treatment for 2 weeks due to HCC, was started on intravenous dextrose for hypoglycemia and steroid, glucagon, and octreotide treatments, respectively. The patient’s sorafenib treatment was discontinued and a second-line palliative chemotherapy was initiated. The patient responded dramatically to octreotide treatment and the need for intravenous glucose gradually decreased. Following approximately six weeks after hospitalization, the patient’s requirement for intravenous glucose was no longer necessary. HCC and its treatment is a complex process involving the activation or inhibition of various mechanisms, and refractory hypoglycemia may rarely be seen in patients with HCC. But the cause of hypoglycemia may not always be identified. In cases where the cause is not understood, other treatment options for hypoglycemia, such as increasing caloric intake, intravenous glucose administration, high-dose steroids, glucagon, and octreotide, should be considered.
Manual Therapy in Patients With Chronic Obstructive Pulmonary Disease: An Overview of Systematic Reviews With Meta-Analysis and Meta-Regression
Authors: Forner-Álvarez Carlos , Cuenca-Martínez Ferran , Sempere-Rubio Núria , Carrasco-González Enrique , Grande-Alonso Mónica , Martínez-Arnau Francisco M.
Published: December 2024

Purpose:

The main aim was to assess the effects of manual therapy (MT) in patients with chronic obstructive pulmonary disease (COPD).

Methods:

We searched in Medline (PubMed), Embase, CINAHL, and Scopus. The outcome measures were pulmonary function parameters (FEV1 and forced vital capacity [FVC]) and exercise capacity. Methodological quality was analyzed using AMSTAR-2. The Graphical Representation of Overlap for OVErviews tool (GROOVE) was used to explore the overlap of primary studies among systematic reviews. Pooled effects were calculated as standardized mean differences (SMDs) and 95% confidence intervals for the outcomes using a random effects model.

Results:

Seven systematic reviews were included, from which a total of 9 primary studies were found. The meta-analysis showed no significant differences in favor of the MT group in FEV1 (SMD = −0.27 [−0.60 to 0.05, P = .051]) and FVC (SMD = −0.40 [−0.83 to 0.04, P = .05]). However, the meta-analysis showed significant differences in favor of the MT group in exercise capacity with a small clinical effect (SMD = −0.47 [−0.71 to −0.23], P < .001). The meta-regression analysis revealed that the intervention time and the number of sessions of MT were not associated with the improvement of pulmonary function parameters (R2 = 0.5%–14.94%, P > .05) nor exercise capacity (R2 = 5.56%–13.56%, P > .05).

Conclusions:

MT does not seem to have a significant impact on the improvement of pulmonary function in patients with COPD, although it appears to improve exercise capacity. Finally, more intervention time as well as more sessions of MT do not seem to result in a greater clinical effect in patients with COPD.
Optimizing Long COVID Outcomes: An Interdisciplinary Survey of U.S. Rehabilitation Providers
Authors: Clancy Malachy J. , Dekerlegand Robert L.
Published: December 2024

Purpose:

Clinical practice guidelines (CPGs) can optimize Long COVID rehabilitation outcomes; however, an understanding of the target condition and available resources influence the adoption of CPGs. This study explored rehabilitation provider's awareness of Long COVID and their use of associated CPGs within the United States.

Methods:

A cross-sectional sample of 300 rehabilitation providers (100 physical therapists, 100 occupational therapists, 100 speech-language pathologists) were randomly selected from the state with the highest prevalence of Long COVID within each of the 9 U.S. geographic divisions. A total of 2700 participants were invited to complete a survey exploring their awareness of Long COVID and use of CPGs.

Results:

Surveys were received from 299 providers (11.6% response rate) across all identified states and disciplines. Most (70.2%) reported awareness of Long COVID symptomatology. Few were aware of relevant CPGs (12.7%) or used them (7.4%) in practice. Although 39.8% reported awareness of symptom exacerbation triggers, only 8.3% knew of associated screening tools. Similar trends were noted when responses were limited to those who treat Long COVID. Nearly all respondents (88.2%) believed that Long COVID will persist in the rehabilitation community.

Conclusion:

Rehabilitation providers perceive that they are aware of Long COVID symptomatology, although there is a lack of awareness and application of relevant CPGs across disciplines. Discrepancies between providers' perceived and actual understanding of Long COVID rehabilitation likely exist that can impede outcomes if evidence-based resources are underused. Interdisciplinary initiatives to enhance evidence translation to rehabilitation are needed to optimize Long COVID practice.
Leukocytosis as a Risk Factor for Coronary Artery Disease: Pathophysiology and Epidemiology
Authors: Amin Toka , Rasool Muhammad Haseeb Ul , Ozkan Bike Ilyada , Swaminathan Gowri , Rauf Faateh , Patrizi Santino , Sethi Arshia , Frishman William H. , Aronow Wilbert S. , Ahmed Mahmoud Samy
Published: December 2024

Coronary artery disease (CAD) is a significant health concern characterized by reduced blood flow to the heart muscle, primarily due to the buildup of atherosclerotic plaques in the coronary arteries. This process begins with endothelial injury, leading to a cascade of biological responses contributing to plaque formation. Endothelial injury attracts the migration of monocytes which differentiate into macrophages upon uptake of oxidized low-density lipoproteins, changing into lipid-laden macrophage or “foam cells.” The process of plaque formation is influenced by many factors which have been studied extensively in literature such as smoking, hypertension, and diabetes mellitus. Chronic inflammatory illnesses are often associated with a high prevalence of coronary artery syndromes, prompting the evaluation of markers of inflammation such as white blood cell count and inflammatory markers as independent risk factors for CAD. White blood cells play a remarkable role in the pathophysiology of disease formation and progression. The article below aims to discuss the pathophysiology and epidemiology of leukocytosis as a risk factor for CAD.
Knowledge of Established Conditions List and Associated Policies and Procedures Among Pediatricians and Early Intervention Personnel
Authors: Yadav Asha , Phelps Randall Alan , Squires Jane
Published: December 2024

Objective:

Despite automatic eligibility, many children with medical conditions associated with increased risk of disability do not receive Early Intervention (EI) services. State EI programs have compiled lists of established conditions to facilitate automatic enrollment; yet little is known about professionals' knowledge and utilization of these lists. This study examined the knowledge of these established conditions lists and associated policies and procedures among pediatricians and EI personnel. State initiatives and approaches undertaken to improve familiarity and utilization of the list, along with recommendations for its improvement were examined.

Method:

In this mixed-methods study, self-rated survey data were collected from 193 EI personnel responsible for intake and eligibility evaluations, and 69 pediatricians providing primary care. Follow-up interviews were then conducted with 45 EI personnel and 22 pediatricians. Quantitative data were analyzed using descriptive statistics, and qualitative data underwent thematic analysis.

Results:

Pediatricians rated their knowledge of their state's established conditions list and related policies and procedures lower than EI personnel. Both groups emphasized the significance of the list in referral and eligibility determination but highlighted its underutilization and lack of professional development activities. Consequently, recommendations were made to improve state established conditions lists and their utilization in ensuring direct EI enrollment for eligible children.

Conclusion:

The lack of shared knowledge and utilization of established conditions lists and associated policies and procedures among pediatricians and EI personnel may result in referral failure for eligible children. Addressing this challenge requires improvement in the content and statewide distribution to improve accessibility and usability.
Six-Year Outcome of Lentigo Maligna Treated with “Spaghetti” Technique and Margin Identification by Reflectance Confocal Microscopy
Authors: Le May Océane , Cinotti Elisa , Perrot Jean-Luc , Tognetti Linda , Chauvel Picard Julie
Published: December 2024

BACKGROUND

Lentigo maligna (LM) and LM melanoma (LMM) present surgical challenges due to their poorly defined boundaries, making it difficult to determine precise peripheral margins. In addition, their preferential localization on the face increases the need to minimize the amount of tissue excised. Striking a balance between reducing the excision size and maintaining oncologic effectiveness is critical in managing LM/LMM. Reflectance Confocal Microscopy (RCM), a noninvasive imaging method that provides cellular-level visualization, could be an ideal tool to define the peripheral margins in the “spaghetti” surgical technique.

OBJECTIVE

This study aimed to evaluate the long-term outcomes of using RCM combined with the “spaghetti” technique for LM/LMM excisions.

MATERIALS AND METHODS

Seventy patients with LM/LMM on the face underwent RCM-guided margin definition followed by the “spaghetti” technique. The sample of patients was the same group of patients included in the authors' 2017 study. The authors subsequently evaluated the effectiveness of the authors' protocol via regular follow-up of the cohort.

RESULTS

A total of 59 LMs and 11 LMMs were included. The mean follow-up time was 6.3 years. The recurrence rate was 5.7%. The authors identified 4 recurrences: 3 of which occurred more than 5 years after the procedure. The recorded mortality was 20%, no deaths were attributed to LM/LMM. The mean margin from lesion to clearance was 2.7 mm.

CONCLUSION

If the authors cluster the 3 principal studies in terms of cohort and follow-up time for LM/LMM treated by Wide local Excision, the recurrence rate is from 5.3% to 5.9%, which is equivalent to the authors'. However, the mean margin excision from lesion is more than 2 times inferior in the authors' protocol (2.7 mm vs 6.7 mm). Therefore, the spaghetti technique with RCM margin identification seems to be an effective method for LM/LMM management.
The Histological Effects of Hyaluronic Acid and Hyaluronidase Injections on Skin: An Experimental Study
Authors: Köken Süleyman , Akşam Ersin , Marşil Rehber , Şimşek Fatma , Başol Tunahan Berk
Published: December 2024

BACKGROUND

Nonsurgical facial rejuvenation procedures are currently among the most popular areas of plastic, reconstructive, and aesthetic surgery. The goal of this study is to identify the effects of simultaneous hyaluronic acid and hyaluronidase injections into animal skin. This study is the first animal study in the literature showing the effects of hyaluronic acid and hyaluronidase simultaneous injection on skin.

METHODS

The study included 15 male and 15 female Wistar Albino rats. Four different areas were determined on the backs of the rats: a control area, an area for injection with hyaluronic acid, an area for injection with hyaluronic acid with hyaluronidase, and an area for injection with hyaluronidase only. The experiment was terminated at different times in these groups. After sacrification, the 4 regions were compared with each other under light microscope.

RESULTS

The results of this study demonstrate increases in dermis thickness, collagen density, and extracellular matrix density with injection of hyaluronic acid (81% vs 69.1%, p < .05), and hyaluronidase appears to antagonize these effects (52.5% vs 59.17%, p < .05).

CONCLUSION

Hyaluronic acid injections have positive effects on animal skin, while hyaluronidase can antagonize these effects. When hyaluronic acid and hyaluronidase are injected simultaneously into the animal skin, it is observed that the antagonizing effect of hyaluronidase is dominant from the first moment.
Laser Test Spot Practices Among Dermatologists
Authors: Wang Jennifer Y. , Patel Paras , Kabakova Margaret , Cohen Marc , Jagdeo Jared
Published: December 2024

BACKGROUND

Laser test spots are a preliminary assessment performed on a small area of the skin to evaluate patients' reaction to laser therapy. Despite their recognized importance, there is a gap in knowledge among dermatologists regarding laser test spot practices.

OBJECTIVE

The authors aim to explore dermatologists' test spot practices.

METHODS

A survey was performed among Association of Academic Cosmetic Dermatology members.

RESULTS

Laser test spot practices varied widely between dermatologists, with 3.0% “always,” 22.7% “frequently,” 54.5% “occasionally,” 16.7% “rarely,” and 3.0% “never” performing test spots. Most dermatologists (59.4%) wait more than 2 weeks before evaluating a test spot. Furthermore, 68.3% of the respondents use the same laser settings for the test spot as they would for the actual treatment. Regarding location, 60.9% of dermatologists perform laser test spots in the same area intended for treatment, while 39.1% choose another inconspicuous area.

CONCLUSION

Establishing definitive protocols for laser test spots may reduce variability in practice and enhance the overall safety and efficacy of laser treatments.
Dose Optimization of Amikacin in the Emergency Department: A Population Pharmacokinetics Simulation Study
Authors: Dia Nada , De Winter Sabrina , Gijsen Matthias , Desmet Stefanie , Vanbrabant Peter , Peetermans Willy , Spriet Isabel , Dreesen Erwin
Published: December 2024

Background:

In adult patients with sepsis or septic shock admitted to the emergency department, a single intravenous 15 mg/kg amikacin dose provides inadequate pharmacokinetic–pharmacodynamic target attainment at the locally reported minimum inhibitory concentration (MIC) of 2 mg/L and the European Committee on Antimicrobial Susceptibility Testing clinical breakpoint for Enterobacterales of 8 mg/L.

Objectives:

To provide an amikacin dosing strategy with a clinically acceptable probability of target attainment (PTA) for all patients.

Methods:

Stochastic simulations were performed using a two-compartment population pharmacokinetics model of amikacin (NONMEM 7.5). PTA was evaluated for various dosing strategies across a range of virtual patients' body weight, body mass index, serum total protein, serum sodium, fluid balance, and estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI), at the locally reported MIC of 2 mg/L and the clinical breakpoint of 8 mg/L. The pharmacokinetic–pharmacodynamic targets were a 24-hour area under the concentration–time curve (AUC24h)/MIC of ≥80 and a 24-hour postdose concentration (C24h) of < 3 mg/L for efficacy and safety, respectively.

Results:

The PTA for the clinical breakpoint of 8 mg/L was <90% with standard 15 mg/kg dosing, across all patient characteristics. A flat 1500-mg dose achieved ≥90% PTA for the entire population at a MIC of 2 mg/L. However, at the clinical breakpoint of 8 mg/L, a flat 3500-mg dose provided ≥90% PTA only when the eGFRCKD-EPI was <96 mL/min/1.73 m2. The C24h was similar for 1500 mg and 15 mg/kg dosing, whereas 3500 mg resulted in a higher C24h.

Conclusions:

A flat dose is recommended over weight-based dosing. However, selecting a 1500-mg or 3500-mg dose may compromise either efficacy (MIC 2 mg/L) or safety (clinical breakpoint 8 mg/L), posing a dilemma. Clinical validation is warranted.
Calcifying Aponeurotic Fibroma in the Deep Space of the Hand
Authors: Antar Ryan M. , Kidwai M. Sulaiman , Brammer Iris , Zhang Athena , Mantilla-Rivas Esperanza , Hussain Ahmad , Oh Albert K. , Rogers Gary F.
Published: December 2024

Calcifying aponeurotic fibroma is a rare tumor that can involve the upper extremity, but deep hand space involvement is exceptionally uncommon and presents unique diagnostic and treatment challenges. We present a 9-year-old girl with a progressively enlarging mass on the ulnar side of the left palm. Magnetic resonance imaging revealed an ill-defined tumor with fatty infiltration spanning the third and fourth metacarpal spaces, suspicious of an aggressive tumor. The delay in diagnosis, likely stemming from the location in the deep space of the palm and lack of functional impairment, allowed this lesion to become atypically large and expansive. Given the child’s age, a marginal excision was performed with careful preservation of the adjacent tendons, bone, and neurovascular structures. Although long-term monitoring for recurrence is ongoing, the patient had no evidence of recurrence at 1-year follow-up.
Chronic total occlusion of renal artery in symptomatic young patient with resistant hypertension: is a revascularization necessary or redundant?
Authors: Stecko Wojciech , Wańczura Piotr , Wajhajmer Adam , Wiśniowski Mateusz , Aebisher David
Published: December 2024

Renal artery stenosis (RAS) can be described as a narrowed vessel lumen at least 60% which hemodynamic significance may be subsequently confirmed by the pressure gradient measuring with endovascular methods. Frequency with which a disease appears in a population is 5–10% and its dominant cause is the occurrence of atherosclerotic plaque. Infrequent causes include fibromuscular dysplasia and vasculitis such as Takayasu arteritis. Diagnostic gold standard of RAS is digital subtraction angiography (DSA) with pressure measurements. Nevertheless, Doppler ultrasonography (DUS), magnetic resonance angiography (MRA) and computed tomography angiography (CTA) may also play a key role during diagnostics process. Revascularization of narrowed or occluded vessel consists of percutaneous transluminal angioplasty (PTA) with balloon, drug-coated balloon or stent implantation. Surgical procedures are rare and dedicated only to treatment-resistant cases.

We reported a 19-year-old patient with resistant arterial hypertension, left ventricular hypertrophy and stenosis of the proximal segment of the right renal artery, confirmed in angio-CT examination. Subsequent follow-up endovascular diagnostic procedure after 12 months revealed complete occlusion of renal artery with angiographic features of chronic total occlusion (CTO). Additionally, laboratory tests showed increase of creatinine level, with an estimated eGFR of 32.9 ml/min/1.73 m2. Considering the whole case – history of fibromuscular dysplasia, deterioration of renal function and the presence of resistant hypertension in a young patient – the invasive treatment was decided. Revascularization with paclitaxel-coated balloon was performed leading to renal perfusion improvement and normalization of the creatinine level. The patient was discharged from hospital with significantly reduced doses of antihypertensive drugs.

There are few publications on opening CTOs of renal arteries. The method is rarely used and research in this field should be extended. While routine revascularization is not recommended, in some cases, we should take under consideration that early restoration of normal renal perfusion can bring benefits to the patient both clinical and related to the number of drugs taken and quality of life.
Use of Online Large Language Model Chatbots in Cornea Clinics
Authors: Nichani Prem A. H. , Ong Tone Stephan , AlShaker Sara M. , Teichman Joshua C. , Chan Clara C.
Published: December 2024

Purpose:

Online large language model (LLM) chatbots have garnered attention for their potential in enhancing efficiency, providing education, and advancing research. This study evaluated the performance of LLM chatbots—Chat Generative Pre-Trained Transformer (ChatGPT), Writesonic, Google Bard, and Bing Chat—in responding to cornea-related scenarios.

Methods:

Prompts covering clinic administration, patient counselling, treatment algorithms, surgical management, and research were devised. Responses from LLMs were assessed by 3 fellowship-trained cornea specialists, blinded to the LLM used, using a standardized rubric evaluating accuracy, comprehension, compassion, professionalism, humanness, comprehensiveness, and overall quality. In addition, 12 readability metrics were used to further evaluate responses. Scores were averaged and ranked; subgroup analyses were performed to identify the best-performing LLM for each rubric criterion.

Results:

Sixty-six responses were generated from 11 prompts. ChatGPT outperformed the other LLMs across all rubric criteria, scoring an overall response score of 3.35 ± 0.42 (83.8%). However, Google Bard excelled in readability, leading in 75% of the metrics assessed. Importantly, no responses were found to pose risks to patients, ensuring the safety and reliability of the information provided.

Conclusions:

ChatGPT demonstrated superior accuracy and comprehensiveness in responding to cornea-related prompts, whereas Google Bard stood out for its readability. The study highlights the potential of LLMs in streamlining various clinical, administrative, and research tasks in ophthalmology. Future research should incorporate patient feedback and ongoing data collection to monitor LLM performance over time. Despite their promise, LLMs should be used with caution, necessitating continuous oversight by medical professionals and standardized evaluations to ensure patient safety and maximize benefits.
Tumor budding is an independent adverse prognostic factor of pancreatic ductal adenocarcinoma patients treated by resection after preoperative chemoradiotherapy
Authors: Hayasaki Aoi , Mizuno Shugo , Usui Miki , Kaluba Benson , Komatsubara Haruna , Sakamoto Tatsuya , Maeda Koki , Shinkai Toru , Noguchi Daisuke , Ito Takahiro , Gyoten Kazuyuki , Iizawa Yusuke , Fujii Takehiro , Tanemura Akihiro , Murata Yasuhiro , Kuriyama Naohisa , Watanabe Masatoshi , Uchida Katsunori , Kishiwada Masashi
Published: December 2024

Objectives

To examine the significance of tumor budding as a prognostic factor of resected pancreatic ductal adenocarcinoma (PDAC) specimens after preoperative chemoradiotherapy (CRT).

Methods

Among 162 PDAC patients who underwent pancreatectomy after gemcitabine and S1-based CRT from 2012 to 2019, 131 were evaluated for tumor budding. Tumor buds were counted at the invasive front, where the degree of budding was the greatest (hematoxylin and eosin staining, ×20 magnification). Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were compared between the patients without tumor budding (non-TB group) and those with tumor buddings (TB group). Multivariate Cox proportional hazards analysis was conducted to examine the significance of tumor budding as a prognostic factor.

Results

OS, DSS, and RFS (median survival time) of the non-TB group were significantly longer than those of the TB group (OS: 50.7 vs. 27.5 months, P = 0.014. DSS: 63.3 vs. 33.0 months, P = 0.014. RFS: 20.3 vs. 11.3 months, P = 0.028). Multivariate analysis identified adjuvant chemotherapy (P = 0.003) as a favorable prognostic factor of OS and tumor budding (P = 0.023) as an adverse prognostic factor of DSS.

Conclusions

This study revealed that the presence of tumor budding was an independent adverse prognostic factor in PDAC patients resected after gemcitabine and S1-based CRT.
Prostate cancer in people with HIV
Authors: Sigel Keith , Yu Ryan , Chiao Elizabeth , Deshmukh Ashish , Leapman Michael S.
Published: December 2024

Purpose of review

Prostate cancer burden has been rising among people with HIV (PWH), yet it remains understudied in the context of HIV infection. The objective of this review article is to summarize contemporary information on the burden, risk, and outcomes of prostate cancer for people living with HIV.

Recent findings

Despite a lower apparent incidence of prostate cancer in early studies for PWH compared to uninfected persons, this malignancy is now likely to be the most common tumor for US PWH. Tumor characteristics and stage appear to have limited differences by HIV status. The optimal approach to early detection of prostate cancer remains controversial, and there are little HIV-specific data surrounding screening. Prostate cancer outcomes may have been worse for PWH in the early antiretroviral era but may have improved in more recent years.

Prostate cancer is an increasingly common clinical issue for PWH. Lower than expected incidence rates in the early ART-era may be increasing, and oncologic outcomes may also be improving. Treatment tolerability is still a key question for this patient group. Given the clinical and biological complexity of chronic HIV infection, strategies for both early detection and treatment will need continued evaluation specifically in the setting of HIV.
Risk of Malignancy Related to Ixekizumab in Patients With Psoriatic Arthritis or Axial Spondyloarthropathy
Authors: Maneiro José Ramón , Carmona Julia , Mera Antonio , Pérez-Pampín Eva
Published: December 2024

Background

We aimed to estimate the risk of malignancy associated with ixekizumab in randomized controlled trials (RCTs) and long-term extension studies (LTEs) in patients with rheumatological indications.

Methods

A systematic review of the literature up to June 2024 was performed to analyze the risk of malignancy associated with ixekizumab use in patients with psoriatic arthritis and axial spondyloarthritis. The primary endpoint was overall malignancy risk in RCTs and LTEs. Meta-analyses of RCTs were performed when at least 3 studies had comparable outcome measures using Peto odds ratios. For LTEs, meta-analyses were performed using random-effects computing incidence rates (IRs) per 100 patient-years.

Results

Twelve articles, 4 LTEs and 8 pooled analyses, were included. Meta-analyses of RCTs for malignancy risk at week 24 showed a Peto odds ratio of 0.45 (0.11–1.86), with an I
2 of 43.0%. When stratified according to the comparator, heterogeneity decreased. Malignancy risk comparing ixekizumab with placebo was 1.43 (0.18–11.53), with an I
2 of 39.6%. Malignancy risk comparing ixekizumab with adalimumab was 0.11 (0.01–0.77), with an I
2 of 0%. At week 52, the IR of all malignancies with ixekizumab was 0.31 (0.07–0.72), with an I
2 of 18.9%. At 156 weeks, the IR of all malignancies with ixekizumab was 0.58 (0.29–0.96), with an I
2 of 0%.

Conclusion

Ixekizumab appears to confer a low malignancy risk in patients treated for rheumatological indications. Patients with psoriatic arthritis and axial spondyloarthritis appeared to be at similar risk, except for those with nonmelanoma skin cancer.
Association Between Quantitative Sialoscintigraphy and Antibody Profiles in Patients With Sjögren or Sicca Syndrome
Authors: Chuang Tzyy-Ling , Koo Malcolm , Lee Yi-Min , Tung Chien-Hsueh , Wang Yuh-Feng
Published: December 2024

Purpose

This study analyzed the association between anti-Ro/SSA and anti-La/SSB antibody levels with quantitative and visual sialoscintigraphy patterns in patients suspected of having Sjögren or sicca syndrome.

Patients and Methods

Medical records of patients who underwent sialoscintigraphy between April 2020 and May 2022 were reviewed. Associations between antibody levels and sialoscintigraphy parameters were evaluated using linear regression. Receiver operating characteristic curve analysis was used to identify antibody cutoff values for predicting flat-type patterns and the risk of Sjögren or sicca syndrome.

Results

Of the 170 patients (mean age, 56.6 years; 78.8% female), 95.3% had dry mouth and eyes, 30% experienced polyarthralgia, and 66.5% were prescribed hydroxychloroquine. The most common sialoscintigraphy finding was the median-type time-activity curve (TAC) pattern. Anti-Ro/SSA and anti-La/SSB levels were significantly correlated with maximum accumulation or maximum secretion in the salivary glands. Receiver operating characteristic analysis for anti-Ro/SSA predicting a flat-type TAC pattern showed an area under the curve (AUC) of 0.659 to 0.780, with specificity between 82.1% and 86.3% for antibody levels greater than 85.2 units. Anti-Ro/SSA levels greater than 49.75 units predicted a higher risk of Sjögren or sicca syndrome, with an AUC of 0.622 and 83.9% specificity. Anti-La/SSB levels had no significant predictive value, with an AUC of 0.554.

Conclusions

Anti-Ro/SSA levels greater than 85.2 units were strong predictors of flat-type TAC patterns, indicating near-total salivary gland dysfunction and supporting their diagnostic utility in Sjögren or sicca syndrome.
American College of Surgeons Cancer Program Annual Report from 2021 Participant User File
Authors: Habermann Elizabeth B , Day Courtney N , Palis Bryan E , Plichta Jennifer K , Wasif Nabil , Weigel Ronald J , Boughey Judy C
Published: December 2024

The National Cancer Database (NCDB) collects data from approximately 1,500 Commission on Cancer (CoC) facilities and represent 73.7% of newly diagnosed cancers nationwide.

The American College of Surgeons Cancer Program developed it first annual report from the NCDB 2021 participant user file reporting new observations and recent trends of cancer diagnoses, patient demographics, and treatments as well as an in-depth report on treatment and outcomes in breast, pancreas, and colon cancers.

Of the 1,328,131 cancers diagnosed in 2021 at 1,281 reporting CoC hospitals, one-fifth continue to be female breast cancer. In 2021, the NCDB’s 5 most common adult cancers were breast, prostate, lung, colon, and melanoma and varied by patient sex. Use of neoadjuvant systemic therapy increased in recent years in pancreas, breast, and urinary bladder cancer, although a slight decrease in pancreas and breast cancer was observed in 2021.

Breast cancer has high survival rates, especially in lower-stage disease and estrogen receptor-positive/human epidermal growth factor receptor 2-negative disease. There is increase in neoadjuvant systemic therapy use, especially in human epidermal growth factor receptor 2-positive disease and estrogen receptor-negative disease.

Colon cancer presents most commonly as stage III or II with a primary in the cecum or ascending colon in 38.9%. The majority are microsatellite instability stable, Kirsten rat sarcoma viral oncogene homologue normal, and CEA positive. Survival is most dependent on stage but also associated with microsatellite instability stability, abnormal Kirsten rat sarcoma viral oncogene homologue, and positive CEA.

Pancreatic cancer presents with stage IV disease in nearly half, although an increase in stage I disease is seen. The most common location is pancreatic head. Survival is relatively low and most dependent on stage.
Sanguibacter biliveldensis sp. nov., a Gram-positive mesophilic bacterium isolated from plant lesions
Authors: Kiel Annika , Helweg Laureen Patricia , Kaltschmidt Bernhard Peter , Wohllebe Max Paul , Hitz Fabian , Hütten Andreas , Knabbe Cornelius , Niehaus Karsten , Staiger Dorothee , Rückert-Reed Christian , Busche Tobias , Kaltschmidt Barbara , Kaltschmidt Christian
Published: December 2024

A bacterial strain was isolated from pathogenic lesions of Acer campestre tree leaves from the Teutoburg Forest in North Rhine-Westphalia, Germany, by culture on non-selective agar plates. 16S rRNA sequencing revealed 100% similarity to Sanguibacter keddieii and Sanguibacter inulinus, as well as 99% similarity to Sanguibacter gelidistatuariae and Sanguibacter antarcticus. Here, we used genome-based taxonomy with the Type (Strain) Genome Server (TYGS), which suggests the isolation of a novel prokaryotic strain. According to TYGS-analysis, using whole genome digital DNA–DNA hybridization, only 65.5% similarity to the closest relative S. inulinus was revealed, suggesting a novel species. Growth was observed at both aerobic and anaerobic conditions. Bacterial cells depicted coryneform motile rods, with a length of 1.1–3.3 µm and a constant diameter of 0.5 µm. Cells did not form spores under the tested conditions and stain Gram-positive. Growth occurred between 0.5 and 4% NaCl (optimal: 1%), at pH 5.5–9.5 (optimal: 8.0–9.0). The strain was mesophilic with an optimal growth at 25 °C. Major cellular fatty acids of the novel strain were anteiso-C15 : 0 and C16 : 0.
Pseudomonas boreofloridensis sp. nov., and Pseudomonas citrulli sp. nov., isolated from watermelon in Florida
Authors: Fullem Kiersten R. , MacLellan Michelle P. , Poudel Mousami , Goss Erica M. , Potnis Neha , Minsavage Gerald V. , Jones Jeffrey B. , Paret Mathews L.
Published: December 2024

Three fluorescent bacterial strains, K1, K13 and K18, were obtained from watermelon (Citrullus lanatus) foliage symptomatic of bacterial leaf spot of cucurbits in Florida. The strains underwent phenotypic characterization, including LOPAT (levan production, oxidase activity, pectolytic activity on potato, arginine dihydrolase production and hypersensitive response (HR) on both tobacco and tomato) and pathogenicity testing on watermelon and squash seedlings. Whole-genome sequencing of the isolates was performed, and multi-locus sequence analysis (MLSA) utilizing housekeeping genes gltA, rpoD, gapA and gyrB placed the isolates into two distinct clades within the Pseudomonas genus. Average nucleotide identity based on blast (ANIb) was used to compare the isolates to Pseudomonas reference genomes. Using ANIb, the closest relatives to the novel strains were identified as Pseudomonas wayambapalatensis (K1 : 82.58%; K13 : 83.77%) and Pseudomonas kilonensis (K18 : 87.16%), although ANIb values were below the 95% threshold for species delineation. DNA–DNA hybridization (genome–genome distance calculation method), comparison to the online Type Genome Server, Biolog biochemical profiling and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were also unable to identify the isolates as any known species of Pseudomonas. Based on the combination of genetic and phenotypic data, we conclude that these isolates represent two novel Pseudomonas species, for which we propose the names Pseudomonas boreofloridensis sp. nov. (K1, K13T, NCPPB 4759=LMG 33364) and Pseudomonas citrulli sp. nov. (K18T, NCPPB 4761=LMG 33365). The specific epithet boreofloridensis was chosen for the geographic location of isolation (northern Florida), while citrulli designates the host of origin (C. lanatus).
Modeling vehicle collision risk for the jungle cat in the Hyrcanian forests of Iran: A guide for vehicle collision prevention
Authors: Ashoori Abbas , Kafash Anooshe , Rabiei Koros , Hosseini Mojtaba , Abdi Shapour , Yousefi Masoud
Published: December 2024

Wildlife-vehicle collisions are an important wildlife conservation challenge, especially for carnivores. As in other countries, vehicle collisions pose a major threat to carnivores in Iran. The jungle cat (Felis chaus) is a small carnivore species facing multiple threats, including habitat destruction, land use changes, and particularly vehicle collisions. We collected data on jungle cat collisions to model jungle cat-vehicle collision risk in the Hyrcanian forests of northern Iran. We also modeled the jungle cat vehicle collision risk in the study area but by creating 1 km and 5 km buffers around the roads and identified high vehicle collision risk areas within the 1 km and 5 km butters. We used the Maxent model to identify most important predictors of collision risk. Our models showed that areas in west of Golestan province, east of Mazandaran province, and in central parts of Gilan province faced highest vehicle collision risk for the jungle cat in the Hyrcanian forests. Human footprint and slope were the most important predictors of the jungle cat vehicle collision, with 48.3% and 17.2% contribution and with positive and negative correlation respectively. Results of variable importance were similar when modeling area was limited to a 5 km buffer zone around the roads. But when modeling area was limited to a 1 km buffer zone around the roads, slope became insignificant. Collisions more likely occur where vegetation grows immediately adjacent to roads, so clearing a roadside strip would reduce potential collisions. We recommend that high collision-risk areas we identified for jungle cat in the Hyrcanian forests be a focus for future monitoring and conservation planning.
GAGER: gene regulatory network assisted gene expression restoration
Authors: Chowdhury Md Zarzees Uddin Shah , Any Sumaiya Sultana , Samee Md. Abul Hasan , Rahman Atif
Published: December 2024

Gene regulatory networks are crucial for cellular function, and disruptions in transcription factor (TF) regulation often lead to diseases. However, identifying TFs to transition a source cell state to a desired target state remains challenging. We present a method to identify key TFs whose perturbation can restore gene expressions in a source state to target levels. Its effectiveness is demonstrated on datasets from yeast TF knockouts, cardiomyocytes from hypoplastic left heart syndrome patients, and mouse models of neurodegeneration. The method accurately identifies knocked-out TFs in the yeast dataset. In the cardiomyocyte dataset, it pinpoints TFs that, though not differentially expressed in many cases, exert significant regulatory influence on downstream differentially expressed genes. Finally, in the mouse model dataset, it identifies disease stage-specific TFs, improving similarity between healthy and diseased states at various time points. Unlike traditional approaches relying on differential expression analysis, our method uses network-based prioritization for more targeted and biologically relevant TF selection. These findings highlight its potential as a therapeutic tool for precise TF targeting to normalize gene expressions in diseased states.
Impact of land cover and climate change on habitat of Indian birds
Authors: Diengdoh Vishesh L. , Srinivasan Umesh
Published: December 2024

Birds play an important role in multiple ecosystems and face significant threats from both land-cover and climate change, the effects of which remain insufficiently understood. This study projected the impact of these global changes on habitat suitability of 478 birds in India, which has the 9thhighest number of bird species globally, under present conditions (2015) and future scenarios (2100) using an ensemble of machine learning algorithms. The results project the average amount of suitable habitat to decrease for non-forest and non-specialised habitat birds but not for forest birds. Suitable habitat was projected to decrease in desert and xeric shrublands and tropical and subtropical-broadleaf forest and grasslands, savannas, and shrublands biomes. We recommend conservation strategies to focus more than they currently do on non-forest birds as well as desert and xeric shrublands and tropical and subtropical broadleaf forest biomes.
Poka: a necro-robot beetle with a measured payload ratio of 6847 %
Authors: Tsvetkov Yordan , Alam Parvez
Published: December 2024

This paper is concerned with the design, manufacture and validation of ‘Poka’, a novel millimetre-scale necro-robot aimed at bridging the performance gap between miniature robots and insects. To create Poka, we use the exoskeleton of a deceased five-horned rhinoceros beetle (Eupatorus gracilicornis) as a mechanical chassis, which is mechatronically functionalised to enable ambulation. When comparing the payload ratio,PR, of Poka against reported values of the rhinoceros beetleXyloryctes thestalus, we find that Poka’sPRis more than 2-fold higher, reaching a measured maximum of 6847% (i.e. 68.47 times its own body weight). The specific power at maximum payload,Ps,t, is nevertheless of the same order of magnitude in bothXyloryctes thestalus(0.21 W/kg) and Poka (0.28 W/kg). Poka’s highest average speed,is achieved at aPR= 2739%, after which it progressively decreases with increasing payload ratio, reaching its minimumat maximum payload ratio. When comparing Poka’s maximum measuredPRof 6847% against those of sixteen other ambulating robots, we find that Poka’sPRfar exceeds that of any other robot to date, the highest being otherwise from SuperBot who has aPR= 530%. Poka’s payload ratio is therefore the highest robot payload ratio recorded to date and we attribute this to (a) the use of the beetle body as a natural composite chassis with high specific properties, and (b) the additive manufacture of bionic beetle parts using low density but stiff polylactic acid, designed with structurally stable geometries.
Cell-type specific subtyping of epigenomes improves prognostic stratification of cancer
Authors: Luo Qi , Teschendorff Andrew E.
Published: December 2024

Background

Most molecular classifications of cancer are based on bulk-tissue profiles that measure an average over many distinct cell-types. As such, cancer subtypes inferred from transcriptomic or epigenetic data are strongly influenced by cell-type composition and do not necessarily reflect subtypes defined by cell-type specific cancer-associated alterations, which could lead to suboptimal cancer classifications.

Methods

To address this problem, we here propose the novel concept of cell-type specific combinatorial clustering (CELTYC), which aims to group cancer samples by the molecular alterations they display in specific cell-types. We illustrate this concept in the context of DNA methylation data of liver and kidney cancer, deriving in each case novel cancer subtypes and assessing their prognostic relevance against current state-of-the-art prognostic models.

Results

In both liver and kidney cancer, we reveal improved cell-type specific prognostic models, not discoverable using standard methods. In the case of kidney cancer, we show how combinatorial indexing of epithelial and immune-cell clusters define improved prognostic models driven by synergy of high mitotic age and altered cytokine signaling. We validate the improved prognostic models in independent datasets, and identify underlying cytokine-immune-cell signatures driving poor outcome.

Conclusions

In summary, cell-type specific combinatorial clustering is a valuable strategy to help dissect and improve current prognostic classifications of cancer in terms of the underlying cell-type specific epigenetic and transcriptomic alterations.
State-specific Peptide Design Targeting G Protein-coupled Receptors
Authors: Xue Yang , Li Jun , Wang Hong , Hu Jianguo , Zheng Zhi , He Jingzhou , Gong Huanzhang , Li Xiangqun , Zhang Xiaonan , Fang Xiaomin
Published: December 2024

G protein-coupled receptors (GPCRs) play critical roles in various physiological processes and serve as pivotal targets for drug discovery. Peptides are particularly compelling therapeutic agents for targeting GPCRs, as they frequently exhibit superior affinity, selectivity, and potency compared to small molecule drugs. However, the dynamic conformational states of GPCRs profoundly influence their interactions with ligands, highlighting the need for state-specific strategies in peptide design. To address this, we developed an efficient state-specific peptide design framework targeting GPCRs. This approach includes an analysis of GPCR state-transition mechanisms and a specially optimized peptide structure prediction model for GPCRs, HelixFold-Multistate, allowing us to evaluate state-specific scores for the designed peptides. On recent GPCR-peptide PDBs, HelixFold-Multistate not only maintains the GPCR active state, similar to AlphaFold-Multistate, but also demonstrates high interaction prediction capabilities comparable to AlphaFold-Multimer in terms of DockQ and iRMS. Experiments on CXCR4-peptide affinity data indicate that its confidence scores exhibit a higher correlation and screening capability than those of AlphaFold-Multistate. By employing this design method, we successfully identified both the agonist and antagonist peptides for the Growth Hormone Secretagogue Receptor (GHSR) and Apelin Receptor (APJ), exhibiting EC50 values below 100 nM and 10 nM respectively. Despite the challenges with antagonist peptides, our method also identified inhibitors for GHSR and APJ, with respective IC50 values of 3.3 μM and 20.3 μM.
Planktonic oyster larvae optimize settlement decisions in complex sensory landscapes
Authors: Schmidlin Sarah , Treherne Yliam , Mees Jan , Hablützel Pascal I.
Published: December 2024

The settlement of pelagic larvae constitutes a pivotal phase in the life cycle of benthic aquatic species. The choice of settlement location is critical for the recruitment to established populations and the colonization of unoccupied habitats. Consequently, the cues governing settlement decisions in larvae become particularly pertinent for human activities such as habitat restoration, mariculture, or biofouling prevention. Our study aims to enhance our comprehension of the underlying principles of how larvae optimize settlement decisions when exposed to multiple natural chemical cues simultaneously. Through a series of laboratory experiments, we investigate settlement patterns of Pacific oysterMagallana gigaslarvae when exposed to different combinations of attractant and repellent cues. Our findings reveal additive increases in settlement rates in the presence of attractant cues originating from conspecifics and biofilms. Conversely, settlement attraction by conspecific water-borne cues was reduced in the presence of repellent cues emanating from predators. Notably, when repellent predator cues were presented alongside attractant cues linked to substrates (biofilms or shells from conspecific adults), the repellent effect was nullified.